WorldWideScience

Sample records for warfarin

  1. Warfarin

    Science.gov (United States)

    Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood ... diarrhea), or an indwelling catheter (a flexible plastic tube that is placed into the bladder to allow ...

  2. Warfarin Overanticoagulation

    OpenAIRE

    2009-01-01

    Warfarin use is associated with appearance of Adverse Drug Reactions like overanticoagulation, this generates in the elderly more morbidity, hospitalized management and increased bleeding risk through associations with another illnesses and drug and food interactions. This anticoagulant is a coumarin which acts through inhibition of extrinsic coagulation pathway factors, because of it’s effect on Vitamin K cycle, and it’s follow with the International Normalized Ratio (INR) finding more hemor...

  3. [Warfarin therapy and hemarthrosis].

    Science.gov (United States)

    Kuperman, Amir; Brenner, Benjamin

    2010-05-01

    Bleeding in patients on oral anticoagulant treatment is not uncommon, but hemarthrosis has been described only in few patients. This is a case report of a patient on warfarin due to recurrent venous and arterial thromboembolism, with congenital thrombophilia and Behcet's disease. This report presents knee hemarthrosis during warfarin therapy, reviews the literature and discusses this issue.

  4. Warfarin and acetaminophen interaction.

    Science.gov (United States)

    Gebauer, Markus G; Nyfort-Hansen, Karin; Henschke, Philip J; Gallus, Alexander S

    2003-01-01

    A 74-year-old man who was receiving warfarin for atrial fibrillation experienced an abrupt increase in his international normalized ratio (INR) after taking acetaminophen. To investigate this effect, the patient's anticoagulation therapy was stabilized, and he was given acetaminophen 1 g 4 times/day for 3 days. His INR rose from 2.3 before receiving acetaminophen to 6.4 on the day after acetaminophen was discontinued. Warfarin was stopped for 2 days, and the patient's INR returned to 2.0. Warfarin was restarted at the same dosage, and his INR remained within 2.0-3.0 for 6 months. Factor VII activity decreased from 29.4% before acetaminophen therapy to 15.5% when his INR was 6.4, and factor X activity fell from 27.0% to 20.2%. His warfarin plasma concentration was 1.54 microg/ml before acetaminophen compared with 1.34 microg/ml when his INR was 6.4. No significant changes in drug intake, clinical status, diet, or lifestyle were noted. Changes in INR of this magnitude with the addition of another drug during stable anticoagulation therapy suggest a drug interaction. The lack of an increase in warfarin plasma concentration associated with the increased INR suggests a possible pharmacodynamic mechanism for this interaction. Acetaminophen or a metabolite may enhance the effect of oral coumarin anticoagulants by augmenting vitamin K antagonism. Thus, the anticoagulant effect of warfarin may be significantly elevated after only a few days of acetaminophen therapy. Patients receiving warfarin should be counseled to have their INR monitored more frequently when starting acetaminophen at dosages exceeding 2 g/day.

  5. Warfarin interaction with Matricaria chamomilla.

    Science.gov (United States)

    Segal, Robert; Pilote, Louise

    2006-04-25

    No cases have been reported of Matricaria chamomilla potentiating the effects of warfarin. Nevertheless there is a theoretical risk for potentiation, since the herb is thought to be a coumarin constituent. We describe the case of a 70-year-old woman who, while being treated with warfarin, was admitted to hospital with multiple internal hemorrhages after having used chamomile products (tea and body lotion) to soothe upper respiratory tract symptoms. Patient education on the potential risk of taking chamomile products while being treated with warfarin is necessary to avoid such occurrences.

  6. Patient's Guide to Taking Warfarin

    Science.gov (United States)

    ... have not incurred the expenses of developing and marketing a new drug. In the United States, trademark ... risk of falling or injury (e.g., contact sports) Warfarin and Lifestyle Changes in daily living can ...

  7. How to manage warfarin therapy.

    Science.gov (United States)

    Tideman, Philip A; Tirimacco, Rosy; St John, Andrew; Roberts, Gregory W

    2015-04-01

    Long-term treatment with warfarin is recommended for patients with atrial fibrillation at risk of stroke and those with recurrent venous thrombosis or prosthetic heart valves. Patient education before commencing warfarin - regarding signs and symptoms of bleeding, the impact of diet, potential drug interactions and the actions to take if a dose is missed - is pivotal to successful use. Scoring systems such as the CHADS2 score are used to determine if patients with atrial fibrillation are suitable for warfarin treatment. To rapidly achieve stable anticoagulation, use an age-adjusted protocol for starting warfarin. Regular monitoring of the anticoagulant effect is required. Evidence suggests that patients who self-monitor using point-of-care testing have better outcomes than other patients.

  8. Genetics Home Reference: warfarin sensitivity

    Science.gov (United States)

    ... SA, Patel M, Martis S, Lubitz SA, van der Zee S, Yoo C, Edelmann L, Halperin JL, Desnick RJ. ... or Free article on PubMed Central van der Zee SA, Halperin JL. Anticoagulant therapy: warfarin sensitivity genotyping ...

  9. Patient factors that influence warfarin dose response.

    Science.gov (United States)

    White, Pamela J

    2010-06-01

    Warfarin has long been the mainstay of oral anticoagulation therapy for the treatment and prevention of venous and arterial thrombosis. The narrow therapeutic index of warfarin, and the complex number of factors that influence international normalized ratio (INR) response, makes optimization of warfarin therapy challenging. Determination of the appropriate warfarin dose during initiation and maintenance therapy requires an understanding of patient factors that influence dose response: age, body weight, nutritional status, acute and chronic disease states, and changes in concomitant drug therapy and diet. This review will examine specific clinical factors that can affect the pharmacokinetics and pharmacodynamics of warfarin, as well as the role of pharmacogenetics in optimizing warfarin therapy.

  10. [Diagnosis and treatment of warfarin resistance].

    Science.gov (United States)

    Tan, Shenglan; Zhou, Xinmin; Li, Zhi; Zhang, Wei; Liu, Zhaoqian; Zhou, Honghao

    2013-03-01

    Warfarin resistance is a phenomenon that patients need to take much higher than normally prescribed dosage of warfarin to maintain the target therapeutic international normalized ratio (INR) range, or even fail to reach the target INR. Warfarin resistance can be categorized in etiologic terms as hereditary vs acquired, or in pharmacologic terms as pharmacokinetic vs pharmacodynamic. Once warfarin resistance is diagnosed, the type of resistance should be determined as soon as possible so that treatment could be oriented toward the causes. Poor compliance, genetic mutations, concurrent medications that could decrease the absorption or increase the clearance of warfarin, and consumption of diet rich in vitamin K are the major reasons for warfarin resistance. Educating patients, increasing warfarin dosage and switching to other anticoagulants would be effective for warfarin resistance.

  11. Genetics Home Reference: warfarin resistance

    Science.gov (United States)

    ... the VKORC1 enzyme, the result is complete warfarin resistance . While changes in specific genes affect how the body reacts ... conditions diagnosed? How are genetic conditions treated or managed? What is genetic testing? How can ... coumarin resistance poor metabolism of coumarin Related Information How are ...

  12. Probable warfarin and dapsone interaction.

    Science.gov (United States)

    Truong, Teresa; Haley, James

    2012-01-01

    We describe a case of a 41-year-old woman who was stable for over a year on 22.5 mg/week of warfarin. At a follow-up visit, her international normalized ratio (INR) was found to be supratherapeutic at 3.9. Her only significant change was acyclovir initiation for shingles, and clindamycin and dapsone for infection on her right foot. An interaction report was run using Micromedex with no interactions reported. Sixteen percent of the weekly dose was held and maintenance dose was continued. Two weeks later, the INR remained supratherapeutic at 4.3, with discontinuation of clindamycin and dapsone, 5 days earlier, as the only change. This time an interaction report was run using Lexi-Comp, which identified an interaction between warfarin and dapsone. The INR has been therapeutic and stable since discontinuation of transient factors. It is hypothesized that warfarin and dapsone compete for binding on the CYP2C9 and CYP3A4 isoenzymes and therefore serum concentration of warfarin was elevated.

  13. Pharmacogenomic dosing of warfarin: ready or not?

    Science.gov (United States)

    Lackner, Thomas E

    2008-08-01

    Warfarin is a medication with a narrow therapeutic index, nonlinear intrapatient pharmacokinetics, and high interpatient variability in its dose-response relationship. These characteristics create great difficulty in determining an appropriate dose; sub- or supratherapeutic doses can increase the risk of bleeding and venous thromboembolism complications. Algorithms based on nongenetic factors of patient age, gender, body weight, diseases, diet, smoking, and medication traditionally have been used to determine warfarin dose requirements. However, these formulas account for less than 20% of the variability in warfarin response. Following completion of the Human Genome Project, several genetic variants of CYP2C9 and VKORC1 have been identified that account for a greater proportion of the variability in patient response to warfarin than is explained by nongenetic factors. Moreover, algorithms that analyze both patient genetic and nongenetic factors, i.e., pharmacogenomics, in warfarin response account for 55% to 60% of the variability. This raises the prospect of enhancing the ability to predict warfarin dose requirements and, thereby, improving its safety, effectiveness, and therapy efficiency. This review evaluates the impact of combining genetic and nongenetic factors in accounting for the variability in warfarin response and the prospect that pharmacogenomic algorithms will improve warfarin dosing early in therapy, possibly achieving a more rapid attainment of the therapeutic dose, improving safety, and increasing effectiveness. The most comprehensive and widely available pharmacogenomic algorithms for estimating warfarin dose requirements when initiating therapy, www.WarfarinDosing.org, is reviewed.

  14. Characterization of Inhibition Kinetics of (S)-Warfarin Hydroxylation by Noscapine: Implications in Warfarin Therapy

    OpenAIRE

    Zhang, Nan; Seguin, Ryan P.; Kunze, Kent L.; ZHANG, YAN-YAN; Jeong, Hyunyoung

    2013-01-01

    Noscapine is an antitussive and potential anticancer drug. Clinically significant interactions between warfarin and noscapine have been previously reported. In this study, to provide a basis for warfarin dosage adjustment, the inhibition kinetics of noscapine against warfarin metabolism was characterized. Our enzyme kinetics data obtained from human liver microsomes and recombinant CYP2C9 proteins indicate that noscapine is a competitive inhibitor of the (S)-warfarin 7-hydroxylation reaction ...

  15. Simplified Warfarin Dose-response Pharmacodynamic Models

    OpenAIRE

    Kim, Seongho; Gaweda, Adam E.; Wu, Dongfeng; Li, Lang; Shesh N Rai; Brier, Michael E.

    2015-01-01

    Warfarin is a frequently used oral anticoagulant for long-term prevention and treatment of thromboembolic events. Due to its narrow therapeutic range and large inter-individual dose-response variability, it is highly desirable to personalize warfarin dosing. However, the complexity of the conventional kinetic-pharmacodynamic (K-PD) models hampers the development of the personalized dose management. To avert this challenge, we propose simplified PD models for warfarin dose-response relationshi...

  16. Warfarin and royal jelly interaction.

    Science.gov (United States)

    Lee, Nancy J; Fermo, Joli D

    2006-04-01

    An 87-year-old African-American man came to the internal medicine clinic for a routine anticoagulation management visit. He had no complaints. His medical history was significant for stage IV-A follicular non-Hodgkin's lymphoma, atrial fibrillation, and hypertension. His long-term drug therapy consisted of warfarin, felodopine, lisinopril-hydrochlorothiazide, controlled-release diltiazem, potassium chloride, and oxycodone. He reported adherence with his prescribed drugs and denied taking any over-the-counter or herbal products. Overall, the patient's drug therapy had been consistent during the preceding 3 months, no significant changes had occurred in his clinical status, and no significant changes had been noted in his diet; his international normalized ratio (INR) had ranged from 1.9-2.4 (therapeutic range 2-3). He denied tobacco use, alcohol consumption, and recent travel. Four weeks later, the patient came to the emergency department with hematuria. He denied dysuria, taking more than the prescribed amount of warfarin, any changes in his diet, taking any over-the-counter or herbal products, and any other bleeding. On admission to the hospital, his INR was 6.88, which increased to 7.29 during his hospital stay. On further investigation, the patient admitted that he had started taking an herbal supplement, royal jelly, 1 week earlier. When asked specifically about the ingredients in the supplement, he stated that royal jelly was the only component. Relative to the patient's denial of any other changes in his condition or drug regimen, the most probable explanation for his elevated INR and subsequent bleeding is a possible interaction between royal jelly and warfarin. To our knowledge, no case reports concerning royal jelly and warfarin taken concomitantly have been reported. Clinicians should be proactive and repeatedly provide education regarding the potential dangers of dietary supplements taken with conventional drugs.

  17. Immunizations in Children Requiring Warfarin Therapy.

    Science.gov (United States)

    Bauman, Mary E; Hawkes, Michael; Bruce, Aisha; Siddons, Suzanne; Massicotte, Patti

    2016-11-01

    Children with conditions requiring chronic warfarin therapy have increased. The importance of receiving immunizations in this population is magnified due to potential weakness in their immune response. There is concern about immunizing on therapeutic anticoagulation due to risk of hematomas and the influence of vaccine on warfarin metabolism. This study evaluated the influence of vaccines on warfarin effect as measured by the International Normalized Ratio and the clinically relevant hematomas or bruising postimmunization. There were no clinically relevant negative outcomes postimmunizations. This study demonstrates that immunizations may be safely administered to children receiving therapeutic warfarin therapy.

  18. Probable warfarin interaction with menthol cough drops.

    Science.gov (United States)

    Coderre, Karen; Faria, Claudio; Dyer, Earl

    2010-01-01

    Warfarin is a widely used and effective oral anticoagulant; however, the agent has an extensive drug and food interaction profile. We describe a 46-year-old African-American man who was receiving warfarin for a venous thromboembolism and experienced a decrease in his international normalized ratio (INR). No corresponding reduction had been made in his warfarin dosage, and no changes had been made in his concomitant drug therapy or diet. The patient's INR fell from a therapeutic value of 2.6 (target range 2-3) to 1.6 while receiving a weekly warfarin dose of 50 mg. His INR remained stable at 1.6 for 3 weeks despite incremental increases in his warfarin dose. The patient reported that he had been taking 8-10 menthol cough drops/day due to dry conditions at his workplace during the time period that the INR decreased. Five days after discontinuing the cough drops, his INR increased from 1.6 to 2.9. Over the subsequent 5 weeks, his INR was stabilized at a much lower weekly warfarin dose of 40 mg. Use of the Naranjo adverse drug reaction probability scale indicated that the decreased INR was probably related to the concomitant use of menthol cough drops during warfarin therapy. The mechanism for this interaction may be related to the potential for menthol to affect the cytochrome P450 system as an inducer and inhibitor of certain isoenzymes that would potentially interfere with the metabolism of warfarin. To our knowledge, this is the second case report of an interaction between warfarin and menthol. Patients receiving warfarin should be closely monitored, as they may choose to take over-the-counter products without considering the potential implications, and counseled about a possible interaction with menthol cough drops.

  19. Genetic warfarin dosing: tables versus algorithms.

    Science.gov (United States)

    Finkelman, Brian S; Gage, Brian F; Johnson, Julie A; Brensinger, Colleen M; Kimmel, Stephen E

    2011-02-01

    The aim of this study was to compare the accuracy of genetic tables and formal pharmacogenetic algorithms for warfarin dosing. Pharmacogenetic algorithms based on regression equations can predict warfarin dose, but they require detailed mathematical calculations. A simpler alternative, recently added to the warfarin label by the U.S. Food and Drug Administration, is to use genotype-stratified tables to estimate warfarin dose. This table may potentially increase the use of pharmacogenetic warfarin dosing in clinical practice; however, its accuracy has not been quantified. A retrospective cohort study of 1,378 patients from 3 anticoagulation centers was conducted. Inclusion criteria were stable therapeutic warfarin dose and complete genetic and clinical data. Five dose prediction methods were compared: 2 methods using only clinical information (empiric 5 mg/day dosing and a formal clinical algorithm), 2 genetic tables (the new warfarin label table and a table based on mean dose stratified by genotype), and 1 formal pharmacogenetic algorithm, using both clinical and genetic information. For each method, the proportion of patients whose predicted doses were within 20% of their actual therapeutic doses was determined. Dosing methods were compared using McNemar's chi-square test. Warfarin dose prediction was significantly more accurate (all p algorithm (52%) than with all other methods: empiric dosing (37%; odds ratio [OR]: 2.2), clinical algorithm (39%; OR: 2.2), warfarin label (43%; OR: 1.8), and genotype mean dose table (44%; OR: 1.9). Although genetic tables predicted warfarin dose better than empiric dosing, formal pharmacogenetic algorithms were the most accurate. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  20. High clearance of (S)-warfarin in a warfarin-resistant subject.

    OpenAIRE

    1993-01-01

    A 30 year old black male required a 60 mg daily dose of warfarin to elicit a therapeutic anticoagulant response (normal warfarin dose 2.5-10 mg day-1; maximum 15 mg day-1). Hereditary warfarin resistance was suspected after compliance, diet, concurrent medication and any gastrointestinal disorder were eliminated as contributory causes. The disposition of vitamin K and vitamin K epoxide was examined in the propositus, his two sisters and 13 control black male subjects. Each subject was given a...

  1. [Fifty years of clinical use of warfarin].

    Science.gov (United States)

    Quintero-González, Jesús Alberto

    2010-06-01

    Warfarin is the most utilized oral anticoagulant for the long term prophylaxes of thrombosis. Its use has been increased as new clinical conditions, capable of leading to thrombosis, have been detected. Due to the special characteristics of warfarin, such as the variability of doses for each individual, the narrow margin between adequate and inadequate doses, interaction with multiple pharmaceutical products, interference of its action by vitamin K present in the diet and the possibility of hemorrhagic complications or thrombotic recurrence, this drug requires a very careful dosage and strict laboratory and clinical monitoring. Despite being in the market for more than de fifty years and its many disadvantages, warfarin has not been substituted for the new oral anticoagulants. In 1999, warfarin was positioned eleventh on the list of the most used medicines in the world.

  2. The complexity of treatment with warfarin

    OpenAIRE

    2006-01-01

    Maintaining a patient within a therapeutic international normalized ratio (INR) is the main aim of treatment with warfarin. Anticoagulation above or below the therapeutic window may result in bleeding or thrombosis respectively. This is made more complex by the numerous factors that may affect warfarin management including other drugs, diet and disease. This review aims to highlight factors that may affect therapy with oral anticoagulants (Figure 1). A sound knowledge of such factors ensures ...

  3. Potential interaction between pomegranate juice and warfarin.

    Science.gov (United States)

    Komperda, Kathy E

    2009-08-01

    To my knowledge, no published reports have described an interaction between pomegranate juice and warfarin. Investigators from previous animal and in vitro studies have reported a potential for pomegranate juice to inhibit metabolism involving the cytochrome P450 system, an effect that could translate into a clinical drug-diet interaction with warfarin. This case report describes a 64-year-old Caucasian woman who was treated with warfarin for recurrent deep vein thrombosis. She had been receiving a relatively stable dosage of warfarin 4 mg/day for several months, with stable international normalized ratios (INRs). During that time, the patient was consuming pomegranate juice 2-3 times/week. She stopped drinking the juice, and her INRs became subtherapeutic. Her dosage of warfarin was increased to maintain therapeutic anticoagulation. No rechallenge with pomegranate juice was performed. Use of the Drug Interaction Probability Scale indicated a possible relationship between the patient's subtherapeutic INR and the pomegranate juice. Although this potential interaction needs to be explored further, clinicians should be aware of the interaction and thoroughly interview and closely monitor their patients who are receiving warfarin.

  4. Potential interactions between alternative therapies and warfarin.

    Science.gov (United States)

    Heck, A M; DeWitt, B A; Lukes, A L

    2000-07-01

    Potential and documented interactions between alternative therapy agents and warfarin are discussed. An estimated one third of adults in the United States use alternative therapies, including herbs. A major safety concern is potential interactions of alternative medicine products with prescription medications. This issue is especially important with respect to drugs with narrow therapeutic indexes, such as warfarin. Herbal products that may potentially increase the risk of bleeding or potentiate the effects of warfarin therapy include angelica root, arnica flower, anise, asafoetida, bogbean, borage seed oil, bromelain, capsicum, celery, chamomile, clove, fenugreek, feverfew, garlic, ginger ginkgo, horse chestnut, licorice root, lovage root, meadowsweet, onion, parsley, passionflower herb, poplar, quassia, red clover, rue, sweet clover, turmeric, and willow bark. Products that have been associated with documented reports of potential interactions with warfarin include coenzyme Q10, danshen, devil's claw, dong quai, ginseng, green tea, papain, and vitamin E. Interpretation of the available information on herb-warfarin interactions is difficult because nearly all of it is based on in vitro data, animal studies, or individual case reports. More study is needed to confirm and assess the clinical significance of these potential interactions. There is evidence that a wide range of alternative therapy products have the potential to interact with warfarin. Pharmacists and other health care professionals should question all patients about use of alternative therapies and report documented interactions to FDA's MedWatch program.

  5. Warfarin in haemodialysis patients with atrial fibrillation: what benefit?

    Science.gov (United States)

    Yang, Felix; Chou, Denise; Schweitzer, Paul; Hanon, Sam

    2010-12-01

    Warfarin is commonly used to prevent stroke in patients with atrial fibrillation; however, patients on haemodialysis may not derive the same benefit from warfarin as the general population. There are no randomized controlled studies in dialysis patients which demonstrate the efficacy of warfarin in preventing stroke. In fact, warfarin places the dialysis patient at increased risk for haemorrhagic stroke and possibly ischaemic stroke. Additionally, warfarin increases the risk of major bleeding and has been associated with vascular calcification. Routine use of warfarin in dialysis for stroke prevention should be discouraged, and therapy should only be reserved for dialysis patients at high risk for thrombo-embolic stroke and carefully monitored if implemented.

  6. Generic switching of warfarin and risk of excessive anticoagulation

    DEFF Research Database (Denmark)

    Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard;

    2015-01-01

    PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis....... METHODS: We conducted a nationwide cohort study based on Danish healthcare registries, including data from the introduction of generic warfarin until the repeal (January 2011-April 2015). We followed Danish warfarin users over time and compared the rate of incident hospitalizations due to excessive...... anticoagulation (i.e. increased INR or any bleeding requiring hospitalization) in periods following a recent switch to generic warfarin to the rate in periods without a recent switch. RESULTS: We included 105 751 warfarin users, filling a total of 1 539 640 prescriptions for warfarin (2.5% for generic warfarin...

  7. The impact of peritransplant warfarin use on renal transplant outcome.

    LENUS (Irish Health Repository)

    Connaughton, Dervla M

    2011-03-31

    The unplanned nature of kidney transplantation necessitates that patients undergo surgery without prior cessation of warfarin. Our study analyses the impact of warfarin treatment in the peritransplant period on graft outcome and perioperative transfusion requirements.

  8. Characterization of inhibition kinetics of (S)-warfarin hydroxylation by noscapine: implications in warfarin therapy.

    Science.gov (United States)

    Zhang, Nan; Seguin, Ryan P; Kunze, Kent L; Zhang, Yan-Yan; Jeong, Hyunyoung

    2013-12-01

    Noscapine is an antitussive and potential anticancer drug. Clinically significant interactions between warfarin and noscapine have been previously reported. In this study, to provide a basis for warfarin dosage adjustment, the inhibition kinetics of noscapine against warfarin metabolism was characterized. Our enzyme kinetics data obtained from human liver microsomes and recombinant CYP2C9 proteins indicate that noscapine is a competitive inhibitor of the (S)-warfarin 7-hydroxylation reaction by CYP2C9. Interestingly, noscapine also inhibited (S)-warfarin metabolism in a NADPH- and time-dependent manner, and removal of unbound noscapine and its metabolites by ultrafiltration did not reverse inhibition of (S)-warfarin metabolism by noscapine, suggesting mechanism-based inhibition of CYP2C9 by noscapine. Spectral scanning of the reaction between CYP2C9 and noscapine revealed the formation of an absorption spectrum at 458 nm, indicating the formation of a metabolite-intermediate complex. Surprisingly, noscapine is a 2- to 3-fold more efficient inactivator of CYP2C9.2 and CYP2C9.3 variants than it is of the wild type, by unknown mechanisms. Based on the inhibitory kinetic data, (S)-warfarin exposure is predicted to increase up to 7-fold (depending on CYP2C9 genotypes) upon noscapine coadministration, mainly due to mechanism-based inactivation of CYP2C9 by noscapine. Together, these results indicate that mechanism-based inhibition of CYP2C9 by noscapine may dramatically alter pharmacokinetics of warfarin and provide a basis for warfarin dosage adjustment when noscapine is coadministered.

  9. Warfarin-Associated Diaphragmatic Hernia: An Unusual Diagnosis

    Directory of Open Access Journals (Sweden)

    Cristina Vilhena

    2015-01-01

    Full Text Available Fetal warfarin syndrome is a consequence of maternal intake of warfarin during pregnancy and comprises a wide range of manifestations, including some typical facial dysmorphologic features. The authors report a case of prenatal ultrasonographic diagnosis of warfarin embryopathy in an obese woman on unsupervised warfarin prophylaxis at the 16th week of gestation. The fetus presented with facial dysmorphism, pectus excavatum, diaphragmatic hernia, and pulmonary hypoplasia. To the best of our knowledge, this is the second reported case of warfarin-associated diaphragmatic hernia.

  10. Pharmacogenetic differences between warfarin, acenocoumarol and phenprocoumon

    NARCIS (Netherlands)

    Beinema, Maarten; Brouwers, Jacobus R. B. J.; Schalekamp, Tom; Wilffert, Bob

    2008-01-01

    Coumarin oral anticoagulant drugs have proven to be effective for the prevention of thromboembolic events. World-wide,warfarin is the most prescribed drug. In Europe, acenocoumarol and phenprocoumon are also administered. Yet it has been proven that variant alleles of the VKORC1 and CYP2C9 genotypes

  11. Is warfarin really underused in patients with atrial fibrillation?

    Science.gov (United States)

    Weisbord, S D; Whittle, J; Brooks, R C

    2001-11-01

    There is agreement that warfarin decreases stroke risk in patients with atrial fibrillation (AF), but prior studies suggest that warfarin is markedly underused, for unclear reasons. To determine if warfarin is underused in the treatment of patients with atrial fibrillation. Cross-sectional. Tertiary care VA hospital. All patients with a hospital or outpatient diagnosis of AF between 10/1/95 and 5/31/98. One or more physician investigators reviewed pertinent records for each patient. When any of the 3 investigators thought warfarin might be indicated, the patient's primary care provider completed a survey regarding why warfarin was not used. Of 1,289 AF patients, 844 (65%) had filled at least 1 warfarin prescription. Of the 445 remaining, 19 had died, 5 had inadequate medical records, and 54 received warfarin elsewhere, leaving 367 patients. Of these, 160 had no documented AF, 53 had only a history of AF, and 49 had only transient AF. Of the remaining 105 patients, 17 refused warfarin therapy and 72 had documented contraindications to warfarin use including bleeding risk or history, fall risk, alcohol abuse, or other compliance problems. The reasons for not using warfarin among the 16 patients remaining included provider oversight (n = 4) and various reasons suggesting provider knowledge deficits. In contrast to prior studies that suggested that warfarin is markedly underused, we found that few patients with AF and no contraindication to anticoagulation were not receiving warfarin. We believe that differing study methodologies, including the use of physician review and provider survey, may explain our markedly different rate of warfarin underutilization, although local institutional factors cannot be excluded. The findings suggest that primary providers may be far more compliant with the standard of care for patients with atrial fibrillation than previously believed.

  12. Warfarin-induced necrosis of the breast: Case report

    Directory of Open Access Journals (Sweden)

    Khalid Kamran

    2004-10-01

    Full Text Available Warfarin-induced necrosis of the breast is an unusual complication of warfarin therapy. Since its first description in 1943, up to 36 cases have been reported in the English literature. Close association between inherited or functional deficiency of protein C and S and warfarin therapy is frequently reported. A characteristic patient is an obese middle-aged female receiving anticoagulant treatment. The rapidly evolving painful lesion appears suddenly, usually within 3 to 6 days after initiation of warfarin therapy. Prevention may be achieved by identifying the high-risk patients-female gender, middle age, obesity, and avoiding large loading doses of warfarin. Early recognition and treatment are necessary to avoid significant long-term morbidity. Established necrosis necessitates debridement and sometimes mastectomy. A case of warfarin-induced necrosis of the left breast mimicking inflammatory cancer is reported. Current recommendations for the prevention and treatment of this uncommon condition are reviewed.

  13. Important Information to Know When You Are Taking: Warfarin (Coumadin) and Vitamin K

    Science.gov (United States)

    ... know when you are taking: Warfarin (Coumadin) and Vitamin K The food you eat can affect how ... information about the interaction between warfarin (Coumadin) and vitamin K. Why was warfarin (Coumadin) prescribed for you? ...

  14. Chinese patients on warfarin therapy : their knowledge and learning experience

    OpenAIRE

    2016-01-01

    Background: Warfarin is a vitamin K antagonist that is the most commonly prescribed anticoagulant, and its continued use is anticipated even with the new anticoagulants. It is well known that warfarin therapy is challenging to manage given its narrow therapeutic range and potential life-threatening side effects, and is well known to have multiple drug-drug, drug-disease and drug-food interactions. The challenge is even greater in a Chinese community as many warfarin-diet interactions are unkn...

  15. Dental extraction in patients on warfarin treatment

    OpenAIRE

    Khalil, Hesham; Abdullah, Walid

    2014-01-01

    Walid Ahmed Abdullah,1,2 Hesham Khalil1 1Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Oral and Maxillofacial Surgery, College of Dentistry, Mansoura University, Mansoura, Egypt Background: Warfarin is one of the most common oral anticoagulants used to prevent thromboembolic episodes. The benefits of discontinuation of this drug before simple surgical procedures are not clear and this approach could b...

  16. Updates on the Clinical Evidenced Herb-Warfarin Interactions

    Directory of Open Access Journals (Sweden)

    Beikang Ge

    2014-01-01

    Full Text Available Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John’s wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I, three were estimated as probable (level II, and ten and twenty-one were possible (level III and doubtful (level IV, respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of “interacting herbs.” In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes.

  17. Graves’ Disease and Treatment Effects on Warfarin Anticoagulation

    Directory of Open Access Journals (Sweden)

    Amanda Howard-Thompson

    2014-01-01

    Full Text Available Background. Hyperthyroidism causes an increased hypoprothrombinemic response to warfarin anticoagulation. Previous studies have demonstrated that patients with hyperthyroidism require lower dosages of warfarin to achieve a therapeutic effect. As hyperthyroidism is treated and euthyroidism is approached, patients may require increasing warfarin dosages to maintain appropriate anticoagulation. We describe a patient’s varying response to warfarin during treatment of Graves’ disease. Case Presentation. A 48-year-old African American female presented to the emergency room with tachycardia, new onset bilateral lower extremity edema, gradual weight loss, palpable goiter, and generalized sweating over the prior 4 months. She was admitted with Graves’ disease and new onset atrial fibrillation. Primary stroke prophylaxis was started using warfarin; the patient developed a markedly supratherapeutic INR likely due to hyperthyroidism. After starting methimazole, her free thyroxine approached euthyroid levels and the INR became subtherapeutic. She remained subtherapeutic over several months despite steadily increasing dosages of warfarin. Immediately following thyroid radioablation and discontinuation of methimazole, the patient’s warfarin dose and INR stabilized. Conclusion. Clinicians should expect an increased response to warfarin in patients with hyperthyroidism and close monitoring of the INR is imperative to prevent adverse effects. As patients approach euthyroidism, insufficient anticoagulation is likely without vigilant follow-up, INR monitoring, and increasing warfarin dosages.

  18. Outcomes in a Warfarin-Treated Population With Atrial Fibrillation

    DEFF Research Database (Denmark)

    Björck, Fredrik; Renlund, Henrik; Lip, Gregory Y H;

    2016-01-01

    IMPORTANCE: Vitamin K antagonist (eg, warfarin) use is nowadays challenged by the non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). NOAC studies were based on comparisons with warfarin arms with times in therapeutic range (TTRs) of 55.2% to 64...

  19. Warfarin use in hemodialysis patients: what is the risk?

    LENUS (Irish Health Repository)

    Phelan, P J

    2012-02-01

    BACKGROUND: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. METHODS: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. RESULTS: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). CONCLUSIONS: This study confirms the higher bleeding risk associated with HD\\/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. SUMMARY: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A

  20. Warfarin use in hemodialysis patients: what is the risk?

    LENUS (Irish Health Repository)

    Phelan, P J

    2011-03-01

    Background: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. Methods: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. Results: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). Conclusions: This study confirms the higher bleeding risk associated with HD\\/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. Summary: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A

  1. Plasma PIVKA proteins in rabbits given warfarin.

    Science.gov (United States)

    Zivelin, A; Rao, L V; Rapaport, S I

    1996-06-01

    The presence of partially carboxylated forms of the vitamin K dependent coagulation factors (PIVKA) was evaluated in the plasma of rabbits treated with warfarin. Excess antigen over activity as measured in rabbit specific assays was taken as evidence for PIVKA. Our data confirm a previous report of the absence of plasma PIVKA prothrombin. In contrast, plasma PIVKA factors VII, IX, and X were demonstrable. A striking excess of plasma factor IX antigen over activity was measured and a large fraction of the factor IX antigen persisted in the plasma after its adsorption with barium citrate.

  2. Pionerer bag vitamin K, dikumarol og warfarin

    DEFF Research Database (Denmark)

    Norn, Svend; Permin, Henrik; Kruse, Edith

    2014-01-01

    . The discovery was initiated by Dam, by a lucky choice of chicks in the dissertation of sterol metabolism, since the vitamin is not formed by intestinal bacteria in these animals. In these experiments the lack of an unknown factor in the synthetic diet caused internal bleeding similar to that found in scurvy......The history of the discovery and development of vitamin K and its antagonists, the oral anticoagulants dicoumarol and warfarin, are fascinating, triumphant landmarks in the annals of medicine. Vitamin K was found by Carl Peter Henrik Dam and Fritz Schønheyder from the University of Copenhagen...

  3. Warfarin and fibrinolysis - a challenging combination: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Luurila Harri

    2011-04-01

    Full Text Available Abstract Background Patients presenting with ST-segment elevation myocardial infarction (STEMI frequently use warfarin. Fibrinolytic agents and warfarin both increase bleeding risk, but only a few studies have been published concerning the bleeding risk of warfarin-prescribed patients receiving fibrinolysis. The objective of this study was to define the prevalence for intracranial haemorrhage (ICH or major bleeding in patients on warfarin treatment receiving pre-hospital fibrinolysis. Methods This was an observational cohort study. Data for this retrospective case series were collected in Helsinki Emergency Medical Service catchment area from 1.1.1997 to 30.6.2010. All warfarin patients with suspected ST-segment elevation myocardial infarction (STEMI, who received pre-hospital fibrinolysis, were included. Bleeding complications were detected from Medical Records and classified as ICH, major or minor bleeding. Results Thirty-six warfarin patients received fibrinolysis during the study period. Fourteen patients had bleeding complications. One (3%, 95% CI 0-15% patient had ICH, six (17%, 95% CI 7-32% had major and seven (19%, 95% CI 9-35% had minor bleeding. The only fatal bleeding occurred in a patient with ICH. Patients' age, fibrinolytic agent used or aspirin use did not predispose to bleeding complications. High International Normalized Ratio (INR seemed to predispose to bleedings with values over 3, but no statistically significant difference was found. Conclusions Bleedings occur frequently in warfarin patients treated with fibrinolysis in the real world setting, but they are rarely fatal.

  4. An update of consensus guidelines for warfarin reversal.

    Science.gov (United States)

    Tran, Huyen A; Chunilal, Sanjeev D; Harper, Paul L; Tran, Huy; Wood, Erica M; Gallus, Alex S

    2013-03-01

    • Despite the associated bleeding risk, warfarin is the most commonly prescribed anticoagulant in Australia and New Zealand. Warfarin use will likely continue for anticoagulation indications for which novel agents have not been evaluated and among patients who are already stabilised on it or have severe renal impairment. • Strategies to manage over-warfarinisation and warfarin during invasive procedures can reduce the risk of haemorrhage. • For most warfarin indications, the target international normalised ratio (INR) is 2.0-3.0 (venous thromboembolism and single mechanical heart valve excluding mitral). For mechanical mitral valve or combined mitral and aortic valves, the target INR is 2.5-3.5. • Risk factors for bleeding with warfarin use include increasing age, history of bleeding and specific comorbidities. • For patients with elevated INR (4.5-10.0), no bleeding and no high risk of bleeding, withholding warfarin with careful subsequent monitoring seems safe. • Vitamin K1 can be given to reverse the anticoagulant effect of warfarin. When oral vitamin K1 is used for this purpose, the injectable formulation, which can be given orally or intravenously, is preferred. • For immediate reversal, prothrombin complex concentrates (PCC) are preferred over fresh frozen plasma (FFP). Prothrombinex-VF is the only PCC routinely used for warfarin reversal in Australia and New Zealand. It contains factors II, IX, X and low levels of factor VII. FFP is not routinely needed in combination with Prothrombinex-VF. FFP can be used when Prothrombinex-VF is unavailable. Vitamin K1 is essential for sustaining the reversal achieved by PCC or FFP. • Surgery can be conducted with minimal increased risk of bleeding if INR ≤ 1.5. For minor procedures where bleeding risk is low, warfarin may not need to be interrupted. If necessary, warfarin can be withheld for 5 days before surgery, or intravenous vitamin K₁ can be given the night before surgery. Prothrombinex-VF use for

  5. Warfarin: do we need genotype-based dose prediction?

    Directory of Open Access Journals (Sweden)

    Yenny Yenny

    2016-02-01

    Full Text Available For the treatment and prevention of thrombo-embolic disease, the most frequently used anticoagulant drug worldwide is warfarin, an oral coumarin derivative, with more than 30 million prescriptions written for this drug in the United States in 2004.(1 The drug has a narrow therapeutic index and its metabolism varies by as much as a factor of 10 among individual patients, making warfarin therapy difficult to manage. Hemorrhagic complication rates of warfarin are estimated to be 5-7.9% for major (life threatening hemorrhage and 14-36% for minor hemorrhage (e.g. nosebleeds, microscopic hematuria.(2 This condition makes it difficult to establish the appropriate dose of warfarin.

  6. Attempted Suicide by Massive Warfarin Ingestion Conservatively Managed Using Phytonadione

    Directory of Open Access Journals (Sweden)

    Katherine L. March

    2016-01-01

    Full Text Available Treatment strategies for acute toxicity following massive ingestion of warfarin are not well described in the literature. Warfarin is the primary oral anticoagulation agent used in the treatment of thromboembolic disease, and patients with acute toxicity are at risk for life-threatening hemorrhages. Treatment options include phytonadione (vitamin K1, fresh frozen plasma (FFP, and prothrombin complex concentrates (PCCs used alone or in combination. FFP and PCC can be associated with volume complications, undesirable thromboembolic events, and increased costs. We describe the case of a 63-year-old female with acute warfarin toxicity following a massive ingestion of warfarin (420 mg–450 mg in an attempt to commit suicide. Upon arrival to the emergency department, serial INR checks were initiated to help guide dosing strategy and later adjusted based on INR response to treatment using only phytonadione.

  7. challenges in management of warfarin anti-coagulation in advanced ...

    African Journals Online (AJOL)

    2013-07-01

    Jul 1, 2013 ... hyper-coagulable state in advanced HIV/AIDS patients has ... state in these patients with abnormalities in the coagulation ... Oral anti-coagulation therapy with warfarin ..... as stasis, trauma, or known hypercoagulability (e.g..

  8. Potential interaction between warfarin and high dietary protein intake.

    Science.gov (United States)

    Hornsby, Lori B; Hester, E Kelly; Donaldson, Amy R

    2008-04-01

    A 55-year-old Caucasian man was receiving warfarin therapy after undergoing aortic valve replacement. His international normalized ratio (INR) was stabilized with warfarin 95 mg/week for 5 weeks. Commencement of a low-carbohydrate, high-protein diet resulted in a series of subtherapeutic INRs that led to a 16% increase in the dosage requirement to maintain therapeutic INRs. After the patient discontinued the diet, his INR increased, and several dosage reductions were required until his INR stabilized with his original dosage of 95 mg/week. Two additional case reports have described a possible interaction between warfarin and a high-protein diet. The potential for increased dietary protein intake to raise serum albumin levels and/or cytochrome P450 activity has been postulated as mechanisms for the resulting decrease in INRs. Given the available animal and human data that demonstrate alterations in drug metabolism in the presence of altered dietary protein intake, an increase in warfarin metabolism due to cytochrome P450 activation appears to be the most likely cause. In addition to the previously reported cases, this case indicates a potential interaction between warfarin and a high-protein diet. Because of the popularity of high-protein diets and because of the risks associated with inadequate or excessive warfarin anticoagulation, patients and health care providers should be aware of this interaction to ensure appropriate monitoring when warranted.

  9. Effect of age and sex on warfarin dosing

    Directory of Open Access Journals (Sweden)

    Khoury G

    2014-07-01

    Full Text Available Ghada Khoury,1 Marwan Sheikh-Taha2 1School of Pharmacy, 2Department of Pharmacy Practice, Lebanese American University, Byblos, Lebanon Objective: We examined the potential effect of sex and age on warfarin dosing in ambulatory adult patients. Methods: We conducted a retrospective chart review of patients attending an anticoagulation clinic. We included patients anticoagulated with warfarin for atrial fibrillation or venous thromboembolism who had a therapeutic international normalized ratio of 2–3 for 2 consecutive months. We excluded patients who had been on any drug that is known to have a major interaction with warfarin, smokers, and heavy alcohol consumers. Out of 340 screened medical records, 96 met the predetermined inclusion criteria. The primary outcome assessed was warfarin total weekly dose (TWD. Results: There was a statistically significant difference in the TWD among the ages (P<0.01; older patients required lower doses. However there was no statistically significant difference in the TWD between sexes (P=0.281. Conclusion: Age was found to have a significant effect on warfarin dosing. Even though women did require a lower TWD than men, this observation was not statistically significant. Keywords: warfarin, INR, anticoagulation, vitamin K antagonists, age

  10. Warfarin dosing after bariatric surgery: a retrospective study of 10 patients previously stable on chronic warfarin therapy.

    Science.gov (United States)

    Schullo-Feulner, A M; Stoecker, Z; Brown, G A; Schneider, J; Jones, T A; Burnett, B

    2014-04-01

    Many changes associated with bariatric surgery have the potential to affect warfarin dosing; yet current literature includes little data describing this phenomenon. Investigating this relationship may allow for determination of post-bariatric surgery warfarin dosing using stable pre-operative dosing levels. A retrospective chart review was completed for 10 patients stabilized on chronic warfarin therapy who underwent bariatric surgery. Data collection consisted of the following: warfarin requirement in mg/week, time in target range (TTR), creatinine, liver function, diarrhoea, medication changes, diet, and signs of bleeding and/or thrombosis. Three study patients underwent laparoscopic adjustable gastric banding procedures and seven patients underwent Roux-en-Y gastric bypass. The average (standard deviation) weekly warfarin dose required in the immediate post-operative interval was 64% (25%) of baseline dosing, corresponding to a TTR of 48%. At 6 months, patients required 85% (19%) of baseline weekly dosing, with TTR of 53.4%. At 1 year, dosing was 90% (16%) of baseline with TTR of 63.5%. Patients underwent medication changes as well as transient bouts of diarrhoea. Two patients suffered unspecified haemorrhages of the gastrointestinal tract (international normalized ratio [INR] = 2.3 and 9.8). This patient set demonstrated an initial drop in warfarin requirement, followed by escalating dosing trends that became more predictable as patients were farther out from procedure.

  11. The potential drug-drug interaction between proton pump inhibitors and warfarin

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Stage, Tore Bjerregaard; Hansen, Morten Rix

    2015-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated...

  12. Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Gislason, Gunnar H.; Lip, Gregory Y.H.

    2015-01-01

    , gastritis, gastric, and duodenal ulcer) and gastrointestinal bleeding requiring hospitalization, gastroscopy, and discontinuation of dabigatran and warfarin was examined by cumulative incidence rates and multivariable adjusted Cox regression models. We identified five groups: OAC-naive warfarin (n = 4534...

  13. Chondrodysplasia punctata after warfarin. Case report with 18-month follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Tamburrini, O.; Bartolomeo-De Iuri, A.; Di Guglielmo, G.L.

    1987-05-01

    Administration of warfarin during pregnancy may cause a rare syndrome characterized by nasal hypoplasia, usually associated with stippled epiphyseal and extraepiphyseal calcifications ressembling chondrodysplasia punctata. A case of chondrodysplasia punctata after warfarin with 18 months follow-up is reported.

  14. A test of financial incentives to improve warfarin adherence

    Directory of Open Access Journals (Sweden)

    Troxel Andrea B

    2008-12-01

    Full Text Available Abstract Background Sub-optimal adherence to warfarin places millions of patients at risk for stroke and bleeding complications each year. Novel methods are needed to improve adherence for warfarin. We conducted two pilot studies to determine whether a lottery-based daily financial incentive is feasible and improves warfarin adherence and anticoagulation control. Methods Volunteers from the University of Pennsylvania Anticoagulation Management Center who had taken warfarin for at least 3 months participated in either a pilot study with a lottery with a daily expected value of $5 (N = 10 or a daily expected value of $3 (N = 10. All subjects received use of an Informedix Med-eMonitor™ System with a daily reminder feature. If subjects opened up their pill compartments appropriately, they were entered into a daily lottery with a 1 in 5 chance of winning $10 and a 1 in 100 chance of winning $100 (pilot 1 or a 1 in 10 chance of winning $10 and a 1 in 100 chance of winning $100 (pilot 2. The primary study outcome was proportion of incorrect warfarin doses. The secondary outcome was proportion of INR measurements not within therapeutic range. Within-subject pre-post comparisons were done of INR measurements with comparisons with either historic means or within-subject comparisons of incorrect warfarin doses. Results In the first pilot, the percent of out-of-range INRs decreased from 35.0% to 12.2% during the intervention, before increasing to 42% post-intervention. The mean proportion of incorrect pills taken during the intervention was 2.3% incorrect pills, compared with a historic mean of 22% incorrect pill taking in this clinic population. Among the five subjects who also had MEMS cap adherence data from warfarin use in our prior study, mean incorrect pill taking decreased from 26% pre-pilot to 2.8% in the pilot. In the second pilot, the time out of INR range decreased from 65.0% to 40.4%, with the proportion of mean incorrect pill taking dropping

  15. Major Interaction between Warfarin and Na Valproate: A Case Report

    Directory of Open Access Journals (Sweden)

    Bizhan Kouchaki

    2015-10-01

    Full Text Available  Abstract: Warfarin is the most commonly used oral anticoagulant drug in clinical practice with extreme inter and intra-individual variation in pharmacokinetic properties. Na Valproate, a broad spectrum anticonvulsant agent, is best known for its enzyme inhibition properties and also displacement of protein binding sites. Interaction between Warfarin and psychotropic drugs including Valproate are important and perhaps under recognized. In this report, we present a 48 year old female patient with chief complaints of abdominal pain, tea-color urine, blurred vision and headache. She had been suffering from "migraine headache" for 15 years that was relatively well controlled with Na Valproate 200mg twice daily. She was experienced a deep vein thrombosis (DVT following oral contraceptive. For management of DVT, she was received Warfarin 5mg/day which was increased to 7.5 mg /day after 2 weeks. Three days after this increment of dose, her Prothrombin Time (PT rose to 35.3 seconds (three times of normal value and evidences of bleeding including hematuria and hematemesis were observed. Based on  the history and laboratory findings, "Warfarin toxicity" was the first impression and she was treated with fresh frozen plasma and vitamin K with a well recovery. This experience emphasizes the clinical significant interaction between Warfarin and Na Valproate, which may take place even with the usual doses of each agent.  

  16. Genetic variants associated with warfarin dosage in Kuwaiti population.

    Science.gov (United States)

    John, Sumi Elsa; Antony, Dinu; Eaaswarkhanth, Muthukrishnan; Hebbar, Prashantha; Alkayal, Fadi; Tuomilehto, Jaakko; Alsmadi, Osama; Thanaraj, Thangavel Alphonse

    2017-06-01

    Assessing the distinct prevalence or absence of genetic variants associated with differential response to the anticoagulant medication of warfarin in different population groups is actively pursued by pharmacogenomics community. Populations from Arabian Peninsula are underrepresented in such studies. By way of examining exome- and genome-wide genotype data from 1395 Arab individuals in Kuwait, we report distinct occurrence of warfarin response-related variants rs12460590_A/CYP2A7, rs2108622_T/CYP4F2, rs2884737_C/VKORC1 and distinct absence of rs11150606_C/PRSS53 in Kuwaiti population. The presented results in conjunction with similar literature reports on Qatari population enhance the worldwide understanding on population-specific distributions of genetic variants associated with warfarin drug dosage.

  17. Strokes attributable to underuse of warfarin and antiplatelets

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Rasmussen, Berit Hammershaimb; Kammersgaard, Lars Peter;

    2007-01-01

    atrial fibrillation, prior myocardial infarction, angina, or prior stroke transient ischemic attack (TIA). Sufficient information on cardiovascular risk factors before stroke was available in 404 patients. A total of 54 patients had atrial fibrillation known before the stroke. Of these, 16 had......Despite their proven efficacy in stroke prevention, warfarin and antiplatelets remain underused. We determined the frequency of ischemic strokes attributable to underuse of warfarin and antiplatelets for stroke prevention in a Danish community. We included all patients with ischemic stroke...... of these strokes could have been prevented. Our findings indicate that underuse of warfarin and antiplatelets is still of considerable magnitude and attributable to 4% to 5% (16 to 22 out of 404) of the ischemic strokes in a Danish urban community....

  18. Patients' perspectives on taking warfarin: qualitative study in family practice

    Directory of Open Access Journals (Sweden)

    Tracy C Shawn

    2004-07-01

    Full Text Available Abstract Background Despite the well-documented benefits of using warfarin to prevent stroke, physicians remain reluctant to initiate therapy, and especially so with the elderly owing to the higher risk of hemorrhage. Prior research suggests that patients are more accepting of the risk of bleeding than are physicians, although there have been few qualitative studies. The aim of this study was to employ qualitative methods to investigate the experience and perspective of individuals taking warfarin. Methods We conducted face-to-face interviews with 21 older patients (12 male, 9 female who had been taking warfarin for a minimum of six months. Participants were patients at a family practice clinic situated in a large, tertiary care teaching hospital. We used a semistructured interview guide with four main thematic areas: decision-making, knowledge/education, impact, and satisfaction. Data were analysed according to the principles of content analysis. Results and Discussion Participants tended to have minimal input into the decision to initiate warfarin therapy, instead relying in great part on physicians' expertise. There appeared to be low retention of information received regarding the therapy; half the patients in our sample possessed only a superficial level of understanding of the risks and benefits. This notwithstanding, participants reported a high level of satisfaction with the care provided and a low level of impact on their day-to-day lives. Conclusions Minimal patient involvement in the initial decision and modest knowledge did not appear to diminish satisfaction with warfarin management. At the same time, care providers exert a tremendous influence on the initiation of warfarin therapy and should strive to incorporate patient preferences and expectations into the decision-making process.

  19. The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study

    OpenAIRE

    2016-01-01

    Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug we...

  20. Clinical and economic consequences of pharmacogenetic-guided dosing of warfarin.

    Science.gov (United States)

    Verhoef, Talitha I; Schalekamp, Tom; Redekop, William K; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

    2010-08-01

    Patients using warfarin for oral anticoagulant therapy need to be frequently monitored because of warfarin's narrow therapeutic range and the large variation in dose requirements among patients. Patients receiving the wrong dose have an increased risk of bleeding or thromboembolic events. The required dose is influenced by environmental factors, such as gender, age, diet and concomitant medication, as well as genetic factors. Pharmacogenetic testing prior to warfarin initiation might improve dosing accuracy and, therefore, safety and efficacy of warfarin treatment. Meckley et al. studied the clinical consequences and costs of genotyping before warfarin treatment. The results of their study suggest that pharmacogenetic-guided dosing of patients initiating warfarin could improve health (quality-adjusted life-years) but at a high cost per quality-adjusted life-year gained. Owing to the inevitable assumptions that have to be made in all cost-effectiveness models, great uncertainty remains regarding the cost-effectiveness of pharmacogenetic-guided warfarin dosing.

  1. Edoxaban versus warfarin in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Giugliano, Robert P; Ruff, Christian T; Braunwald, Eugene

    2013-01-01

    BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing t...

  2. Edoxaban versus warfarin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Giugliano, R.P.; Ruff, C.T.; Braunwald, E.; Murphy, S.A.; Wiviott, S.D.; Halperin, J.L.; Waldo, A.L.; Ezekowitz, M.D.; Weitz, J.I.; Spinar, J.; Ruzyllo, W.; Ruda, M.; Koretsune, Y.; Betcher, J.; Shi, M.; Grip, L.T.; Patel, S.P.; Patel, I.; Hanyok, J.J.; Mercuri, M.; Antman, E.M.; Verheugt, F.W.A.

    2013-01-01

    BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two

  3. Sub-Tenon's anesthesia with aspirin, warfarin, and clopidogrel.

    Science.gov (United States)

    Kumar, Nishant; Jivan, Sharmila; Thomas, Peter; McLure, Hamish

    2006-06-01

    To review the frequency of hemorrhagic complications with sub-Tenon's anesthesia in patients on aspirin, warfarin or clopidogrel. St. James's University Hospital, Leeds, United Kingdom. Data were collected prospectively for patients having elective phacoemulsification under sub-Tenon's anesthesia. Seventy-five patients were on aspirin, 65 were on warfarin, and 40 were on clopidogrel. Seventy-five patients on no anticoagulants were used as the control group. No changes in the anticoagulant regimen were made prior to surgery. No sight-threatening hemorrhagic complications were noted, and no surgery was postponed or cancelled due to an anesthesic complication. Subconjunctival hemorrhage occurred in 19% in the control group, 40% in the clopidogrel group, 35% in the warfarin group, and 21% in the aspirin group. The warfarin and clopidogrel groups had the highest incidence of subconjunctival hemorrhage (P<.05). The incidence of hemorrhages involving more than 1 quadrant was highest in these 3 groups; however, this did not achieve statistical significance (P = .37, Fisher exact test). Data from this study support the continued use of anticoagulant agents among routine users during cataract surgery using a sub-Tenon's block.

  4. Warfarin pharmacogenomics: recommendations with available patented clinical technologies.

    Science.gov (United States)

    Borkowski, Andrew A; Kardani, Avni; Mastorides, Stephen M; Thomas, L Brannon

    2014-01-01

    Warfarin pharmacogenomic testing has become a prime example of the utility of personalized molecular testing in the modern clinical laboratory. Warfarin is a commonly used drug for the prevention and treatment of thromboembolic complications in a variety of clinical situations. However, a number of factors lead to a high interindividual variability in dose requirements. Among the primary factors in this variability are genetic polymorphisms in general patient populations, which can account for 35-50% of varying dose requirements among patients. In this review, we discuss the implications of polymorphisms in the cytochrome P-450 enzyme 2C9 (CYP2C9) and Vitamin K Epoxide Reductase Enzyme Complex subunit 1 (VKORC1) as they relate to therapeutic warfarin dosing. We discuss the clinical utility of pharmacogenomics testing as related to warfarin dosing, and propose a clinical model for the implementation of the pharmacogenomic test results. Finally, we provide a brief overview of the currently available commercial testing platforms with discussion of the complexities of utilizing patented methodologies in bringing genetic testing such as this to the clinical laboratory.

  5. Interaktion mellem warfarin og oral miconazol-gel

    DEFF Research Database (Denmark)

    Ogard, C G; Vestergaard, Henrik

    2000-01-01

    We report a case of a 76 year-old woman who had been taking warfarin for seven years because of relapsing deep venous thrombosis. Her daily maintenance dose was 5 mg. Monthly measurements of international normalised ratio (INR) were stable between 2-3. She developed oral candidiasis and miconazole...

  6. Edoxaban versus warfarin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Giugliano, R.P.; Ruff, C.T.; Braunwald, E.; Murphy, S.A.; Wiviott, S.D.; Halperin, J.L.; Waldo, A.L.; Ezekowitz, M.D.; Weitz, J.I.; Spinar, J.; Ruzyllo, W.; Ruda, M.; Koretsune, Y.; Betcher, J.; Shi, M.; Grip, L.T.; Patel, S.P.; Patel, I.; Hanyok, J.J.; Mercuri, M.; Antman, E.M.; Verheugt, F.W.A.

    2013-01-01

    BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two

  7. Strokes attributable to underuse of warfarin and antiplatelets

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Rasmussen, Berit Hammershaimb; Kammersgaard, Lars Peter

    2007-01-01

    in a Copenhagen community with 302,000 inhabitants admitted to the hospital between September 1999 and May 2000 (n = 426). Patients who did not receive warfarin or antiplatelet medication even though they were at known risk for cardiovascular disease before the incident stroke were identified; they had known...

  8. Fluconazole-Warfarin Interaction: A case report with deadly consequences

    Directory of Open Access Journals (Sweden)

    Elliot V Hersh

    2017-06-01

    Full Text Available Adverse drug-drug interactions are more common in the elderly because of the commonality of polypharmacy. When one of the interacting drugs has a low therapeutic index, the consequences can be life-threatening or fatal. This case describes a fatal cerebral haemorrhage in an 80-year old male on stable doses of warfarin prescribed by his cardiologist, who was prescribed fluconazole 200mg, once daily, for 14 days by an oral and maxillofacial surgeon to treat an intraoral fungal infection. The oral surgeon was aware that the patient was on warfarin and his INR two days prior to the appointment was 2.4. While a drug interaction alert was sent to the patient’s primary care family physician regarding fluconazole and the simvastatin she had been prescribing, the interaction was not reviewed by her for another 9- days. She then informed the patient that “it was fine” to finish the fluconazole. However, this phone conversation prompted the patient to discontinue the fluconazole after 8 doses. Two days later, the patient was confused and driving his car erratically. His son rushed him to the hospital where a CAT scan revealed a large frontal intraparenchymal haemorrhage. His INR was a 9.6. This event illustrates that this well-documented adverse drug interaction needs to be better highlighted in dental and medical training. Warfarin’s primary metabolic pathway involves the cytochrome P-450 2C9 isoform and fluconazole is a strong inhibitor of this enzyme, with the potential outcome being excessive warfarin blood levels. Frequent INR monitoring with potential warfarin dosage adjustments downward if fluconazole is prescribed, or the complete avoidance of fluconazole is recommended in patients taking warfarin. The importance of communication and coordinated care between different health care providers cannot be overstated.

  9. Randomised comparison of a simple warfarin dosing algorithm versus a computerised anticoagulation management system for control of warfarin maintenance therapy.

    Science.gov (United States)

    Nieuwlaat, Robby; Hubers, Lowiek M; Spyropoulos, Alex C; Eikelboom, John W; Connolly, Benjamin J; Van Spall, Harriette G C; Schulze, Karleen M; Cuddy, Spencer M; Stehouwer, Alexander C; Schulman, Sam; Connolly, Stuart J

    2012-12-01

    Excellent control of the international normalised ratio (INR) is associated with improved clinical outcomes in patients receiving warfarin, and can be achieved by anticoagulation clinics but is difficult in general practice. Anticoagulation clinics have often used validated commercial computer systems to manage the INR, but these are not usually available to general practitioners. It was the objective of this study to perform a randomised trial of a simple one-step warfarin dosing algorithm against a widely used computerised dosing system. During the period of introduction of a commercial computerised warfarin dosing system (DAWN AC) to an anticoagulation clinic, patients were randomised to have warfarin dose adjustment done according to recommendations of the existing warfarin dosing algorithm or to those of the computerised system. The study tested if the computerised system was non-inferior to the existing algorithm for the primary outcome of time in therapeutic INR range of 2.0-3.0 (TTR), with a one-sided non-inferiority margin of 4.5%. There were 541 patients randomised to commercial computerised system and 527 to the algorithm. Median follow-up was 159 days. A dose recommendation was provided and followed in 91% of occasions for the computerised system and in 90% for the algorithm (p=0.03). The mean TTR was 71.0% (standard deviation [SD] 23.2) for the computerised system and 71.9% (SD 22.9) for the algorithm (difference 0.9% [95% confidence interval: -1.4% to 4.1%]; p-value for non-inferiority=0.002; p-value for superiority=0.34). In conclusion, similar maintenance control of the INR was achieved with a simple one-step dosing algorithm and a commercial computerised management system.

  10. SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

    Directory of Open Access Journals (Sweden)

    E. L. Artanova

    2011-01-01

    Full Text Available Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, amiodarone therapy were considered among clinical characteristics. Results. Adjusted warfarin dose was significantly higher in obesity , and it was lower in case of experienced myocardial infarction. The INR highest levels and maximal amplitudes of its fluctuations were observed in patients with thyroid gland nodes and smokers. Period of warfarin dose titration was longer in patients treated with amiodarone. Conclusion. Warfarin dose titration in patients with atrial fibrillation depends on the presence of myocardial infarction, obesity , thyroid nodular changes, smoking and amiodarone treatment.

  11. Racial background is a determinant factor in the maintenance dosage of warfarin.

    Science.gov (United States)

    Gan, Gin Gin; Teh, Alan; Goh, Kim Yen; Chong, Heng Thay; Pang, Kang Wah

    2003-07-01

    Warfarin is a drug commonly used in the prevention of thromboembolic events. There have been reports suggesting that racial background may influence warfarin dose requirements. Malaysia is a multiracial country in which there are 3 major races, Malay, Chinese, and Indian. We examined 100 patients from our hospital on stable maintenance doses of warfarin, with international normalized ratio (INR) of 2.0 to 3.5. We found that the mean warfarin dose for Indian patients (n = 19) was 6.9 mg, for Chinese patients (n = 55) was 3.6 mg, and for Malay patients (n = 26) was 3.2 mg. The results showed that the Indian patients required a statistically significantly higher warfarin dose than did patients of the other 2 races (P < .0005). Age was also found to affect the daily warfarin maintenance dose.

  12. Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Jee Eun Park

    2016-03-01

    Full Text Available Warfarin skin necrosis (WSN is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.

  13. Edoxaban versus warfarin in patients with atrial fibrillation.

    Science.gov (United States)

    Giugliano, Robert P; Ruff, Christian T; Braunwald, Eugene; Murphy, Sabina A; Wiviott, Stephen D; Halperin, Jonathan L; Waldo, Albert L; Ezekowitz, Michael D; Weitz, Jeffrey I; Špinar, Jindřich; Ruzyllo, Witold; Ruda, Mikhail; Koretsune, Yukihiro; Betcher, Joshua; Shi, Minggao; Grip, Laura T; Patel, Shirali P; Patel, Indravadan; Hanyok, James J; Mercuri, Michele; Antman, Elliott M

    2013-11-28

    Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P

  14. Warfarin pharmacology, clinical management, and evaluation of hemorrhagic risk for the elderly.

    Science.gov (United States)

    Jacobs, Laurie G

    2006-02-01

    Elderly patients as a group may present more of a challenge in managing warfarin therapy because of alterations in pharmacokinetics from other medications, diet, and disease; pharmacodynamic changes; increased risk for hemorrhage; and difficulty in monitoring. The elderly, however, may derive the most benefit from warfarin therapy for certain indications, such as the prevention of stroke in atrial fibrillation or recurrent events following deep venous thrombosis. Warfarin can be managed as effectively as in other populations with careful attention to these issues.

  15. Clinical and economic consequences of pharmacogenetic-guided dosing of warfarin

    OpenAIRE

    2010-01-01

    textabstractPatients using warfarin for oral anticoagulant therapy need to be frequently monitored because of warfarins narrow therapeutic range and the large variation in dose requirements among patients. Patients receiving the wrong dose have an increased risk of bleeding or thromboembolic events. The required dose is influenced by environmental factors, such as gender, age, diet and concomitant medication, as well as genetic factors. Pharmacogenetic testing prior to warfarin initiation mig...

  16. Brand name versus generic warfarin: a systematic review of the literature.

    Science.gov (United States)

    Dentali, Francesco; Donadini, Marco P; Clark, Nathan; Crowther, Mark A; Garcia, David; Hylek, Elaine; Witt, Dan M; Ageno, Walter

    2011-04-01

    The use of generic drugs has become increasingly common in clinical practice. However, for drugs with a narrow therapeutic index, such as warfarin, there may be some concern regarding the definition of bioequivalence. Clinical studies that compared brand name and generic warfarin products provided conflicting results. Therefore, we performed a systematic review of the literature to better assess the characteristics of each generic warfarin product. Several sources were searched, including MEDLINE and EMBASE, electronic records of meetings' abstracts, and reference lists of included articles. Articles were considered relevant if they were original studies, enrolled patients receiving oral anticoagulant treatment, and compared any approved generic warfarin with brand name warfarin in at least one clinical, laboratory, or management outcome. Eleven studies, with a total of more than 40,000 patients, were included; five were randomized controlled trials, and six were observational studies. In three crossover trials evaluating the mean difference of the international normalized ratio (INR) after switching to the alternate formulation of warfarin, no statistically significant difference was found between patients randomly assigned to receive brand name or generic warfarin. The two other randomized trials found no significant differences in the magnitude or number of dosage changes between patients switched to brand name or generic warfarin. The results of the observational studies are more conflicting, suggesting different features for different generic warfarin products. In these observational studies, the time in the therapeutic range and the number of thromboembolic and hemorrhagic complications were similar in studies that compared the anticoagulation control before and after the switch to a generic warfarin product. In one observational study, however, a change in therapeutic INR control after the switch to generic warfarin was reported at the individual patient

  17. Aspirin versus warfarin in atrial fibrillation: decision analysis may help patients' choice.

    LENUS (Irish Health Repository)

    Romero-Ortuno, Roman

    2012-03-01

    the primary prevention of ischaemic stroke in chronic non-valvular atrial fibrillation (AF) typically involves consideration of aspirin or warfarin. CHA(2)DS(2)-VASc estimates annual stroke rates for untreated AF patients, which are reduced by 60% with warfarin and by 20% with aspirin. HAS-BLED estimates annual rates of major bleeding on warfarin. The latter risk with aspirin is 0.5-1.2% per year.

  18. "Stealth" alerts to improve warfarin monitoring when initiating interacting medications.

    Science.gov (United States)

    Koplan, Kate E; Brush, Alan D; Packer, Marvin S; Zhang, Fang; Senese, Margaret D; Simon, Steven R

    2012-12-01

    As electronic health records (EHRs) become widely adopted, alerts and reminders can improve medication safety, but excessive alerts may irritate or overwhelm clinicians, thereby reducing their effectiveness. We developed a novel "stealth" alert in an EHR to improve anticoagulation monitoring for patients prescribed a medication that could interact with warfarin. Instead of alerting the prescribing provider, the system notified a multidisciplinary anticoagulation management service, so that the prescribing clinicians never saw the alerts. We aimed to determine whether these "stealth" alerts increased the frequency of anticoagulation monitoring following the co-prescription of warfarin and a potentially interacting medication. We conducted a pre-post intervention study, analyzed using an interrupted time-series, within a large, multispecialty group practice that uses a common EHR. The study included a 12-month period preceding the intervention, a 2-month period during intervention implementation, and a 6-month post-intervention period. The primary outcome measure was the proportion of patients completing anticoagulation monitoring within 5 days of a new co-prescribing event. Prior to implementation of the stealth alert, 34 % of patients completed anticoagulation monitoring within 5 days after the prescription of a medication with a potential warfarin interaction. After implementation of the alert, 39 % completed testing within 5 days (odds ratio 1.24, 95 % confidence interval 1.12-1.37). Stealth alerts increased the proportion of patients who underwent anticoagulation monitoring following the prescription of a medication that could potentially interact with warfarin. This team-based approach to clinical-decision support directs alerts away from prescribing clinicians and toward individuals who can directly implement them.

  19. Gastrointestinal Hemorrhage in Warfarin Anticoagulated Patients: Incidence, Risk Factor, Management, and Outcome

    Directory of Open Access Journals (Sweden)

    Wen-Chi Chen

    2014-01-01

    Full Text Available Background. Warfarin reduces the incidence of thromboembolism but increases the risk of gastrointestinal bleeding (GIB. GIB during warfarin anticoagulation is rarely evaluated in Asian patients. Aims. This study aimed at investigating the incidence, risk factors, management, and outcome of GIB in Taiwanese patients treated with warfarin. Methods. We analyzed a cohort of warfarin anticoagulated patients between July 1993 and May 2012. Clinical data were retrieved in a chart-reviewing manner. Results. A total of 401 warfarin anticoagulated patients were enrolled. The incidence of GIB was 3.9% per patient-years. Multivariate analysis with Cox regression showed that age >65 years old (RR: 2.5, 95% CI: 1.2–5.5, a mean international normalized ratio >2.1 (RR: 2.1, 95% CI: 1.0–4.2, a history of GIB (RR: 5.1, 95% CI: 1.9–13.5, and cirrhosis (RR: 6.9, 95% CI: 2.0–24.5 were independent factors predicting GIB. 27.3% of the GIB patients had rebleeding after restarting warfarin while thromboembolic events were found in 16.7% of the patients discontinuing warfarin therapy. Conclusions. Warfarin was associated with a significant incidence of GIB in Taiwanese patients. The intensity of anticoagulation should be monitored closely during warfarin therapy, especially in patients with risk factors of GIB.

  20. Fluorescence enhancement of warfarin induced by interaction with beta-cyclodextrin.

    Science.gov (United States)

    Vasquez, Jacob M; Vu, Andrew; Schultz, Jerome S; Vullev, Valentine I

    2009-01-01

    Warfarin is the most common agent used for control and prevention of venous as well as arterial thromboembolism (blood clots). In aqueous media, warfarin forms inclusion complexes with a family of cyclic oligosaccharides, alpha, beta, gamma-cyclodextrins (CD). The formation of these complexes results in enhancement of the fluorescence of warfarin. Such spectroscopic changes offer a venue for the development of bioanalytical methodologies for warfarin quantification in biological liquids. We characterized the photophysical properties of warfarin in solvents with varying polarity and viscosity. The fluorescence quantum yield of warfarin correlated: (1) strongly with the solvent viscosity (R = 0.979) and (2) weakly with the solvent polarity (R = 0.118). These findings indicate that it is the change of the viscosity, rather than polarity, of the microenvironment that causes the fluorescence enhancement of warfarin upon binding to beta-CD. Utilizing the observed fluorescence enhancement in fluorescence titration measurements, the binding constants of warfarin to beta-CD were obtained (2.6 x 10(2) M(-1)-3.7 x 10(2) M(-1)). Using multivariable linear analysis, we extracted the stoichiometry of warfarin-beta-CD interaction (1:1).

  1. The Impact of Warfarin on Patients with End Stage Renal Disease

    Directory of Open Access Journals (Sweden)

    Anahita Dua

    2014-01-01

    Full Text Available Introduction. A deficiency in vitamin K through the utilization of warfarin may result in increased vascular calcification and complications. This study aimed to determine the impact of warfarin administration on patients with end stage renal disease (ESRD in a large, national sample. Methods. A retrospective analysis using the 2005–2010 National Inpatient Sample (NIS, a part of the Health Care Utilization Project (HCUP, was completed using ICD-9 diagnosis codes to capture patients with ESRD prescribed and not prescribed warfarin. Statistical analysis was through ANOVA and chi-squared testing. Results. From 2005–2010, 927,814 patients with ESRD were identified nationally. 3.5% (32,737 were prescribed warfarin. Patients prescribed warfarin had an average age of 64 years and 51% were male. For every comorbid condition (amputation, congestive heart failure, chronic obstructive pulmonary disorder, cerebrovascular accident, diabetes, hypertension, myocardial infarction, peripheral vascular diasese, and valvular disease patients prescribed Warfarin had significantly higher rates of disease as compared to their nonwarfarin ESRD counterparts. ESRD patients prescribed warfarin had significantly shorter length of stay but increased hospital charges. They were more likely to be discharged to home and had significantly decreased in-hospital mortality. Conclusion. Patients with ESRD taking warfarin are more likely to have comorbidities and/or complications but have a decreased LOS and in-hospital mortality compared to their ESRD counterparts not administered warfarin.

  2. Effect of warfarin on the kinetics of the vitamin K-dependent clotting factors in rats.

    Science.gov (United States)

    Vainieri, H; Wingard, L B

    1977-05-01

    The objectives of this study were to compare the time course of activities and rates of synthesis of activities for the separate clotting factors II, VII, IX, and X and to relate the rate of synthesis of activity of each factor to the plasma concentration of warfarin in individual rats after acute and chronic dosing with warfarin. Sequences of blood samples were obtained from each rat for 50 to 70 hours after an acute dose of warfarin or for 120 hours after a chronic loading dose plus 12-hour maintenance doses of warfarin and assayed for factor activities and warfarin concentration. The half-lives for degradation of factor activities ranged from 2.6 to 9.0 hours for the four factors. During periods of changing warfarin concentration (acute dosing) factor VII and X activities and rates of synthesis of activity showed large rapid changes, while factors II and IX responded more slowly. As the warfarin concentration diminished, the factor X rate of synthesis of activity appeared to exceed predrug values in all rats. During chronic dosing with warfarin the factor II activity and rate of synthesis of activity was depressed the most. The percent depression of the rate of synthesis of activity for each factor was related linearly to the logarithm of the plasma concentration of warfarin for the range 0 to 80% depression with acute dosing. However, this relationship was not suitable to explain the apparent overshoot in factor X rate of synthesis of activity.

  3. Warfarin accelerates ectopic mineralization in Abcc6(-/-) mice: clinical relevance to pseudoxanthoma elasticum.

    Science.gov (United States)

    Li, Qiaoli; Guo, Haitao; Chou, David W; Harrington, Dominic J; Schurgers, Leon J; Terry, Sharon F; Uitto, Jouni

    2013-04-01

    Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. Warfarin, a commonly used anticoagulant, is associated with increased mineralization of the arterial blood vessels and cardiac valves. We hypothesized that warfarin may accelerate ectopic tissue mineralization in PXE, with clinical consequences. To test this hypothesis, we developed a model in which Abcc6(-/-) mice, which recapitulate features of PXE, were fed a diet supplemented with warfarin and vitamin K1. Warfarin action was confirmed by significantly increased serum levels of oxidized vitamin K. For mice placed on a warfarin-containing diet, quantitative chemical and morphometric analyses revealed massive accumulation of mineral deposits in a number of tissues. Mice fed a warfarin-containing diet were also shown to have abundant uncarboxylated form of matrix Gla protein, which allowed progressive tissue mineralization to ensue. To explore the clinical relevance of these findings, 1747 patients with PXE from the approximately 4000 patients in the PXE International database were surveyed about the use of warfarin. Of the 539 respondents, 2.6% reported past or present use of warfarin. Based on the prevalence of PXE (approximately 1:50,000), thousands of patients with PXE worldwide may be at risk for worsening of PXE as a result of warfarin therapy.

  4. Pharmacokinetics and pharmacodynamics of warfarin when coadministered with pentosan polysulfate sodium.

    Science.gov (United States)

    Modi, Nishit B; Kell, Sherron; Simon, Mary; Vargas, Ramon

    2005-08-01

    The effect of pentosan polysulfate sodium on warfarin pharmacokinetics and pharmacodynamics was investigated in healthy subjects. Warfarin was titrated to an international normalized ratio between 1.4 and 1.8. Subjects continued their titrated dose of warfarin and received pentosan polysulfate sodium 100 mg or placebo every 8 hours for 7 days. The Cmax of R- and S-warfarin was approximately 840 to 890 ng/mL and 680 to 730 ng/mL, respectively, and was similar in the absence and presence of pentosan polysulfate sodium. The half-life for R- and S-warfarin was 52 to 56 hours and 36 to 40 hours, respectively. Prothrombin time, partial thromboplastin time, and the international normalized ratio for warfarin + placebo and warfarin + pentosan polysulfate sodium were comparable. The AUC(INR) indicated no treatment effect (P = .772); however, there was a period effect. Analysis of variance for the treatments by period indicated no treatment effect (P > .1). Adverse events were mild and included headache, epistaxis, and rash. Most adverse events were unrelated to treatment and were seen during warfarin titration. Pentosan polysulfate sodium did not affect warfarin pharmacokinetics or pharmacodynamics.

  5. Dabigatran in the Treatment of Warfarin-Induced Skin Necrosis: A New Hope

    Directory of Open Access Journals (Sweden)

    Christos Bakoyiannis

    2016-01-01

    Full Text Available Warfarin-induced skin necrosis is an infrequent and well-recognized complication of warfarin treatment. The incidence was estimated between 0.01% and 0.1% whereas a paradoxal prothrombotic state that arises from warfarin therapy seems to be responsible for this life-threatening disease. To the best of our knowledge we present the first case of an old woman diagnosed with warfarin-induced skin necrosis, in whom novel oral anticoagulants and extensive surgical debridement were combined safely with excellent results.

  6. Dabigatran in the Treatment of Warfarin-Induced Skin Necrosis: A New Hope.

    Science.gov (United States)

    Bakoyiannis, Christos; Karaolanis, Georgios; Patelis, Nikolaos; Maskanakis, Anastasios; Tsaples, Georgios; Klonaris, Christos; Georgopoulos, Sotirios; Liakakos, Theodoros

    2016-01-01

    Warfarin-induced skin necrosis is an infrequent and well-recognized complication of warfarin treatment. The incidence was estimated between 0.01% and 0.1% whereas a paradoxal prothrombotic state that arises from warfarin therapy seems to be responsible for this life-threatening disease. To the best of our knowledge we present the first case of an old woman diagnosed with warfarin-induced skin necrosis, in whom novel oral anticoagulants and extensive surgical debridement were combined safely with excellent results.

  7. Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database.

    Science.gov (United States)

    Liu, Rong; Li, Xi; Zhang, Wei; Zhou, Hong-Hao

    2015-01-01

    Multiple linear regression (MLR) and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20%) and the mean absolute error (MAE) were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling. BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84-8.96 mg/week, mean percentage within 20%: 45.88%-46.35%). In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values algorithms' performances exist among the races. Moreover, machine learning-based algorithms tended to perform better in the low- and high- dose ranges than MLR.

  8. A Comparison of Dabigatran With Warfarin for Stroke Prevention in Atrial Fibrillation in an Asian Population.

    Science.gov (United States)

    Yap, Lok Bin; Eng, Daniel Theng Sheng; Sivalingam, Lingghesh; Rusani, Beni Isman; Umadevan, Dhanan; Muhammad, Zulkeflee; Koh, Kok Wei; Aisha, Barveen; Hashim, Mohd Irwan; Rebo, Rosila; Hussin, Azlan; Kaur, Surinder; Shanmugam, Rajasingam; Omar, Razali

    2016-11-01

    The Asian population with atrial fibrillation (AF) have a higher risk of stroke than the caucasian population and a higher risk of intracranial bleeding when anticoagulated with warfarin. There are few real-world studies comparing the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin among Asian patients to assess its outcomes of ischemic stroke and hemorrhagic stroke. A retrospective cohort study of 1000 patients on dabigatran and warfarin from 2009 to 2013. Data were available for 500 patients on dabigatran and 500 patients on warfarin. The average follow-up duration was 315 ± 280 days in the dabigatran group and 355 ± 232 in the warfarin group. The time in therapeutic range (TTR) was 53.2% in the warfarin-treated group, with 32.8% of patients in the subtherapeutic international normalized ratio range of CVA) compared to 4 (0.8%) patients in the warfarin group, hazard ratio (HR) 0.13, P = .3. There was 1 (0.2%) patient in both dabigatran and warfarin groups with hemorrhagic CVA (HR 1.16, P = .92). There were 3 (0.6%) patients with major bleeding in the dabigatran group compared to 2 (0.4%) patients in the warfarin group (HR 1.57, P = .59). There were similar rates of efficacy for outcomes of ischemic CVA, hemorrhagic CVA, and bleeding when comparing dabigatran with warfarin. Our study shows that despite similar efficacy, suboptimal TTR rates and inconveniences with warfarin demonstrate that NOACs are preferred for stroke prevention in AF. © The Author(s) 2015.

  9. Influence of fatty acids on the binding of warfarin and phenprocoumon to human serum albumin with relation to anticoagulant therapy

    DEFF Research Database (Denmark)

    Vorum, H; Honoré, B

    1996-01-01

    Warfarin and phenprocoumon binding to human serum albumin was studied by equilibrium dialysis. The first stoichiometric binding constant was 1.89 x 10(5) M-1 for warfarin and 2.40 x 10(5) M-1 for phenprocoumon. The affinity of warfarin was markedly increased on addition of up to 3 mol mol-1 albumin...

  10. Initiation and persistence with warfarin therapy in atrial fibrillation according to ethnicity

    DEFF Research Database (Denmark)

    Hansen, Carolina Malta; Olesen, Jonas Bjerring; Hansen, Morten Lock;

    2012-01-01

    The aim of this study was to investigate initiation of and persistence with warfarin treatment in patients with atrial fibrillation (AF) according to ethnicity. Patients hospitalized with first-time AF from 1997 to 2009, prescription claims of warfarin and country of birth were identified by indi...

  11. Menthol reduces the anticoagulant effect of warfarin by inducing cytochrome P450 2C expression.

    Science.gov (United States)

    Hoshino, Motohiro; Ikarashi, Nobutomo; Tsukui, Makoto; Kurokawa, Asako; Naito, Rina; Suzuki, Midori; Yokobori, Kohsuke; Ochiai, Takumi; Ishii, Makoto; Kusunoki, Yoshiki; Kon, Risako; Ochiai, Wataru; Wakui, Nobuyuki; Machida, Yoshiaki; Sugiyama, Kiyoshi

    2014-06-02

    Recently, it was reported that the anticoagulant effect of warfarin was reduced when patients receiving warfarin also took menthol. The purpose of this study is to reveal the mechanism of this reduced anticoagulant effect of warfarin from the pharmacokinetic point of view. Warfarin was orally administered to mice 24h after the administration of menthol for 2 days, and the plasma warfarin concentration was measured. In the menthol administration group, the area under the blood concentration time curve of warfarin was decreased by approximately 25%, while total clearance was increased to 1.3-fold compared to the control group. The hepatic cytochrome P450 (CYP) 2C protein expression level in the menthol administration group was significantly increased compared to that in the control group. An increase in the nuclear translocation of constitutive androstane receptor (CAR) was also observed. The addition of menthol to human hepatic cells, HepaRG cells, caused an increase in the mRNA expression level of CYP2C9. The results of this study revealed that menthol causes an increase in CYP2C expression levels in the liver, which leads to an enhancement of warfarin metabolism, resulting in a decreased anticoagulant effect of warfarin. It was also suggested that menthol acted directly on the liver and increased the expression level of CYP2C by enhancing the nuclear translocation of CAR.

  12. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial

    NARCIS (Netherlands)

    Alexander, J.H.; Lopes, R.D.; Thomas, L.; Alings, M.; Atar, D.; Aylward, P.; Goto, S.; Hanna, M.; Huber, K.; Husted, S.; Lewis, B.S.; McMurray, J.J.; Pais, P.; Pouleur, H.; Steg, P.G.; Verheugt, F.W.A.; Wojdyla, D.M.; Granger, C.B.; Wallentin, L.

    2014-01-01

    AIMS: We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). METHODS AND RESULTS: In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was le

  13. Metabolism of R- and S-Warfarin by CYP2C19 into Four Hydroxywarfarins

    Science.gov (United States)

    Kim, So-Young; Kang, Ji-Yeon; Hartman, Jessica H.; Park, Sun-Ha; Jones, Drew R.; Yun, Chul-Ho; Boysen, Gunnar; Miller, Grover P.

    2013-01-01

    Coumadin (R/S-warfarin) is a highly efficacious and widely used anticoagulant; however, its highly variable metabolism remains an important contributor to uncertainties in therapeutic responses. Pharmacogenetic studies report conflicting findings on the clinical relevance of CYP2C19. A resolution to this controversy is impeded by a lack of detail on the potential role of CYP2C19 in warfarin metabolism. Consequently, we assessed the efficiency of CYP2C19 metabolism of R- and S-warfarin and explored possible contributions in the liver using in vitro methods. Recombinant CYP2C19 metabolized R- and S-warfarin mainly to 6-, 7-, and 8-hydroxywarfarin, while 4′-hydroxywarfarin was a minor metabolite. Overall R-warfarin metabolism was slightly more efficient than that for S-warfarin. Metabolic pathways that produce R-6-, 7-, and 8-hydroxywarfarin in human liver microsomal reactions correlated strongly with CYP2C19 S-mephenytoin hydroxylase activity. Similarly, CYP1A2 activity toward phenacetin correlated with formation of R-6 and 7-hydroxywarfarin such that R-8-hydroxywarfarin seems unique to CYP2C19 and possibly a biomarker. In following, CYP2C19 likely impacts R-warfarin metabolism and patient response to therapy. Intriguingly, CYP2C19 may contribute to S-warfarin metabolism in patients, especially when CYP2C9 activity is compromised due to drug interactions or genetic polymorphisms. PMID:23331088

  14. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack

    DEFF Research Database (Denmark)

    Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R

    2012-01-01

    In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients ...

  15. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial

    NARCIS (Netherlands)

    Alexander, J.H.; Lopes, R.D.; Thomas, L.; Alings, M.; Atar, D.; Aylward, P.; Goto, S.; Hanna, M.; Huber, K.; Husted, S.; Lewis, B.S.; McMurray, J.J.; Pais, P.; Pouleur, H.; Steg, P.G.; Verheugt, F.W.A.; Wojdyla, D.M.; Granger, C.B.; Wallentin, L.

    2014-01-01

    AIMS: We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). METHODS AND RESULTS: In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was

  16. Vitamin K: a practical guide to the dietary management of patients on warfarin.

    Science.gov (United States)

    Booth, S L; Centurelli, M A

    1999-09-01

    Warfarin has been successfully used in the medical management of thromboembolic disease for nearly six decades. It is widely assumed that a dietary vitamin K-warfarin interaction exists. To avoid this potential interference with the efficacy of warfarin in stable anticoagulation, patients typically receive instructions to consume a constant dietary intake of vitamin K. While dark, green vegetables are primary sources of dietary vitamin K, these foods are not commonly consumed on a daily basis in the United States. However, there still exists dietary resistance to warfarin that is attributable to vitamin K. Based on food analysis studies on vitamin K, it is now known that dietary vitamin K is found in certain plant oils and prepared foods containing these plant oils, such as baked goods, margarines, and salad dressings. The preparation of foods with vitamin K-rich oils may also contribute to a diet-warfarin interaction, although this has yet to be confirmed in a clinical trial. A dose-response of vitamin K on the effect of warfarin anticoagulation has not yet been established. However, there are sufficient data to suggest that a constant dietary intake of vitamin K that meets current dietary recommendations of 65-80 micrograms/day is the most acceptable practice for patients on warfarin therapy. Vitamin K composition data for commonly consumed foods are now available and may facilitate successful anticoagulation for patients being treated with warfarin.

  17. Clinical and economic consequences of pharmacogenetic-guided dosing of warfarin

    NARCIS (Netherlands)

    T.I. Verhoef (Talitha); T. Schalekamp (Talitha); W.K. Redekop (Ken); A.C. de Boer (Anthonius); A-H. Maitland-van der Zee (Anke-Hilse)

    2010-01-01

    textabstractPatients using warfarin for oral anticoagulant therapy need to be frequently monitored because of warfarins narrow therapeutic range and the large variation in dose requirements among patients. Patients receiving the wrong dose have an increased risk of bleeding or thromboembolic events.

  18. Clinical and genetic determinants of warfarin pharmacokinetics and pharmacodynamics during treatment initiation.

    Directory of Open Access Journals (Sweden)

    Inna Y Gong

    Full Text Available Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD model. Individual PK (S-warfarin clearance and PD (I(max parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for I(max were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II and weight. Importantly, indication for warfarin was a major independent determinant of I(max during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy.

  19. Study of warfarin utilization in hospitalized patients: analysis of possible drug interactions.

    Science.gov (United States)

    Guidoni, Camilo Molino; Camargo, Helen Palmira Miranda; Obreli-Neto, Paulo Roque; Girotto, Edmarlon; Pereira, Leonardo Regis Leira

    2016-10-01

    Background Drug-drug interactions in patients taking warfarin may contribute to a higher risk of adverse events. Objective To identify and evaluate the prevalence and characteristics of potential DDIs with warfarin. Methods A cross-sectional study was performed in a Brazilian tertiary hospital. The electronic prescriptions of the patients receiving warfarin between January 2004 and December 2010 were analyzed. Socio-demographic, clinical, and therapeutic variables were collected. Warfarin drug-drug interactions were classified as either risk A, B, C, D, or X according to the Lexi-Interact™ Online database. Results A total of 3048 patients were identified who were prescribed warfarin. Of the 154,161 total drug prescriptions issued, 42,120 (27.3 %) were for warfarin. Evaluation of the prescriptions showed that 63.1 and 0.1 % of patients received concomitant drugs classified as having class D or X risk. It was found that 20,539 (48.7 %) prescriptions had at least one drug with a D or X risk. Patients were prescribed an average of 1.4 (±0.4) concomitant medications with a class D or X warfarin-DDI risk, the most frequent being acetylsalicylic acid and amiodarone. Conclusion The results demonstrate a high prevalence of concomitant drug prescriptions with the potential for clinically relevant DDIs with warfarin, the most frequent being acetylsalicylic acid and amiodarone.

  20. Genetic polymorphisms of patients on stable warfarin maintenance therapy in a Ghanaian population.

    Science.gov (United States)

    Kudzi, William; Ahorhorlu, Samuel Yao; Dzudzor, Bartholomew; Olayemi, Edeghonghon; Nartey, Edmund Tetteh; Asmah, Richard Harry

    2016-12-09

    Warfarin is a widely prescribed anticoagulant with narrow therapeutic window for thromboembolic events. Warfarin displays large individual variability in dose requirements. The purpose of this study is to assess the contribution of patient-specific and genetic risk factors to dose requirements of patients on either high or low warfarin maintenance dose in Ghana. Blood samples were collected from 141 (62 males, 79 females) Ghanaian patients on stable warfarin dose to determine their INR. Influence of patient specific factors and gene variations within VKORC1, CYP2C9 and CYP4F2 were determined in patients on either high or low warfarin maintenance dose. One hundred and forty-one patients took part in the study with 79 (56%) participants being Female. The median age of the study participants was 48 years [IQR: 34-58]. The median duration for patients to be on warfarin therapy was 24 months [IQR: 10-72]. Majority of the study participants (80.9%, n = 114) did not have any side effects to warfarin. CYP2C9*2 and CYP2C9*3 variant alleles were not detected. VKORC1 variant allele was observed at 6% and CYP4F2 variant allele was observed at 41%. Duration of patients on warfarin therapy was marginally associated with high warfarin dose (adjusted OR = 1.01 [95% CI 1.00-1.02], p = 0.033) while the odds of heterozygous individuals (G/A) for VKORC1 gene to have high warfarin dose compared to persons with homozygous (G/G) (adjusted OR = 0.06 [95% CI 0.01-0.63], p = 0.019). Age, gender, diagnosis, presence of side effects and other medications were not associated with warfarin dose (p = 0.05). This study provides data on VKORC1 and CYP4F2 variants among an indigenous African population. Duration of patients on warfarin therapy was marginally associated with high warfarin dose. CYP2C9*2 and *3 variants were not detected and may not be the most important genetic factor for warfarin maintenance dose among Ghanaians.

  1. Effects of Atorvastatin on Warfarin-induced Aortic Medial Calcification and Systolic Blood Pressure in Rats

    Institute of Scientific and Technical Information of China (English)

    Chengyun LIU; Jingjing WAN; Qunfang YANG; Benling QI; Wen PENG; Xuelin CHEN

    2008-01-01

    Summary: The effect of atorvastatin on warfarin-induced aortic medial calcification and systolic blood pressure (SBP) of rats induced by warfarin was studied. Thirty healthy and adult rats were randomly divided into Warfarin group (n=10), Atorvastatin group (n=10) and normal control group (n=10). Caudal arterial pressure of rats was measured once a week, and 4 weeks later, aorta was obtained. Elastic fiber, collagen fiber and calcium accumulation in tunica media of cells were measured by Von Kossa staining. The results showed that warfarin treatment led to elevation of systolic blood pressure and aortic medial calcification. The chronic treatment also increased collagen, but decreased elastin in the aorta. However, the atorvastatin treatment had adverse effects. It was concluded that treatment with atorvastatin presented evidence of blood pressure lowing and calcification reducing. These data demonstrate that atorvastatin protected aortic media from warfarin-induced calcification and elevation of systolic blood pressure.

  2. Bleeding due to a probable interaction between warfarin and Gouqizi (Lycium Barbarum L.

    Directory of Open Access Journals (Sweden)

    Jinhua Zhang

    2015-01-01

    Full Text Available Unlike what is widely anticipated by the public, herbal medicines are not always safe despite being natural. We describe a 65-year-old Chinese man taking a prolonged maintenance dose of warfarin who experienced an elevated international normalized ratio (INR with associated bleeding after drinking Gouqizi (goji berry wine. This report illustrates that large doses (more than 6–12 g of Gouqizi can significantly enhance the anticoagulant action of warfarin and may cause similar adverse effects in keeping with three previous reports. Therefore, the use of herbal medicines must adhere to pharmacopoeia-recommended guidelines, including dosage regimes. Doctors should advise patients regarding possible interactions between herbs and warfarin when prescribing and should increase the frequency of INR monitoring for those patients concurrently receiving warfarin and medicinal herbs. Further study is needed to do for the mechanism of interaction between Gouqizi and warfarin.

  3. Effectiveness and safety of a 10mg warfarin initiation nomogram in Asian population.

    Science.gov (United States)

    Chandriah, Haarathi; Kumolosasi, Endang; Islahudin, Farida; Makmor-Bakry, Mohd

    2015-05-01

    Anticoagulant responses to warfarin vary among patients, based on genetic factors, diet, concomitant medications, and disease state. We evaluated the effectiveness and safety of a 10mg warfarin initiation nomogram in an Asian population. Retrospective cross-sectional audit studies were conducted from March 2009 to March 2010. The use of a 10mg-loading dose to initiate warfarin treatment resulted in 33(84.6%) patients attaining a therapeutic INR within four days (mean time, 2.6 days). There was no significant correlation between age, gender, race, and serum albumin for the time to reach a therapeutic INR. A significant correlation was noted for patient's baseline INR and time to reach a therapeutic INR (Pwarfarin nomogram was effective in rapidly achieving a therapeutic INR. However, the nomogram's safety is debatable owing to the high over-anticoagulation rate warfarin-administered patients. Caution is recommended in the initiation of warfarin treatment using the 10mg nomogram.

  4. Increase in international normalized ratio after smoking cessation in a patient receiving warfarin.

    Science.gov (United States)

    Evans, Mark; Lewis, Geoffrey M

    2005-11-01

    A 58-year-old man who was taking warfarin at a stable dosage was admitted to the hospital with a diagnosis of bacterial meningitis. Although he had previously been a smoker, after this admission, he decided to give up smoking. He was continued on his previous warfarin maintenance dosage when discharged, and his international normalized ratio (INR) soon began to climb substantially. When questioned, the patient reported no diet or lifestyle changes other than his smoking cessation. The patient's INR was stabilized at a warfarin dosage 23% lower than the maintenance dosage before he stopped smoking. This case report illustrates the potential for an interaction between warfarin and cigarette smoking and further suggests that the effect could be significant if a patient starts or stops smoking during warfarin therapy.

  5. [On the history of vitamin K, dicoumarol and warfarin].

    Science.gov (United States)

    Norn, Svend; Permin, Henrik; Kruse, Edith; Kruse, Poul R

    2014-01-01

    The history of the discovery and development of vitamin K and its antagonists, the oral anticoagulants dicoumarol and warfarin, are fascinating, triumphant landmarks in the annals of medicine. Vitamin K was found by Carl Peter Henrik Dam and Fritz Schønheyder from the University of Copenhagen. The discovery was initiated by Dam, by a lucky choice of chicks in the dissertation of sterol metabolism, since the vitamin is not formed by intestinal bacteria in these animals. In these experiments the lack of an unknown factor in the synthetic diet caused internal bleeding similar to that found in scurvy, but the bleeding was not reversed by vitamin C and it could not be explained by the lack of classical vitamins. In 1935 the unknown antihaemorrhagic factor was named vitamin K and a few months later the phenomenon was also observed by H.J. Almquist and E.L.R. Stokstad in Berkeley. The activity of the factor was determined by bioassay in different extracts of green vegetables and alfalfa by Dam and Schønheyder. Vitamin K was isolated in 1939 by Dam and Paul Karrer in Zurich and the structure was determined by Edward Adelbert Doisy. Dam and Doisy were awarded the Nobel Prize in 1943. A dramatic story starts the discovery of dicoumarol. In the 1920s cattle in Canada began dying of internal bleeding with no obvious precipitating cause. Frank W. Schofield, a veterinary pathologist in Alberta, found that the mysterious disease was connected to the consumption of spoiled sweet clover hay and noted a prolonged clotting time. Ten years after a farmer traveled in a blizzard with his dead cow and a milk can of the unclotted blood to the University of Wisconsin. Only the door to the biochemical department of Karl Paul Link was open. This event started the isolation of the anticoagulant agent dicou- marol which was formed by microbial induced oxidation of coumarin in the mouldy sweet clover hay. More than hundred dicoumarol-like anticoagulants were synthesized by Link and his co

  6. Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Tolou-Ghamari

    2016-04-01

    Full Text Available Context For the prevention and management of thromboembolic complications, warfarin is the most extensively recommended anticoagulant. It is categorized as a drug with a narrow therapeutic window. Therefore, warfarin prescription requires special attention related to therapeutic drug monitoring. Evidence Acquisition By categorizing the clinical implications of warfarin, this manuscript aims to provide a comprehensive (albeit somewhat brief conclusion associated with its pharmacotherapy. The key words relevant to the topic were searched. Consequently, articles relevant to the pharmacotherapeutic management of warfarin were selected and reviewed in their entirety. Results To obtain a reasonable level of stability between the required antithrombotic treatment and the risk of bleeding, an analysis of the literature revealed that the prothrombin time in terms of the international normalized ratio (INR was found for each individual. The best model for stable warfarin dosage prediction was found to be based on multiple linear regression. Genotype-guided procedures were established to: 1, improve the time in the therapeutic range; 2, reduce time to the first therapeutic INR; and 3, reduce the time for the stable doses. Vitamin K epoxide reductase is an enzyme with an important role in vitamin K metabolism, and warfarin is metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9. In patients carrying 2C9*1/*2 and 2C9*2/*2 or 2C9*1/*3 alleles, the dose is recommended to be reduced by 18% - 40% and 21% - 49%, respectively. Conclusions Race, age, body surface area, chronic kidney disease, CYP2C9*3 level, and VKORC1 variants could affect the dose of warfarin. To administer the proper doses of warfarin, patients and physicians might achieve the best results with the pharmacologist proficient anticoagulation database and recommended continuation program. Owing to its’ unpredictability, caution must be taken when prescribing warfarin. More advanced

  7. Genetic factors associated with patient-specific warfarin dose in ethnic Indonesians

    Directory of Open Access Journals (Sweden)

    Utama Andi

    2011-06-01

    Full Text Available Abstract Background CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual variability in warfarin dose. Additionally, genes in the warfarin metabolism pathway have also been associated with dose variance. We analyzed Single Nucleotide Polymorphisms (SNPs in these genes to identify genetic factors that might confer warfarin sensitivity in Indonesian patients. Methods Direct sequencing method was used to identify SNPs in CYP2C9, VKORC1, CYP4F2, EPHX1, PROC and GGCX genes in warfarin-treated patients. Multiple linear regressions were performed to model the relationship warfarin daily dose requirement with genetic and non-genetic variables measured and used to develop a novel algorithm for warfarin dosing. Results From the 40 SNPs analyzed, CYP2C9 rs17847036 and VKORC1 rs9923231 showed significant association with warfarin sensitivity. In our study population, no significant correlation could be detected between CYP2C9*3, CYP2C9C-65 (rs9332127, CYP4F2 rs2108622, GGCX rs12714145, EPHX1 rs4653436 and PROC rs1799809 with warfarin sensitivity. Conclusions VKORC1 rs9923231 AA and CYP2C9 rs17847036 GG genotypes were associated with low dosage requirements of most patients (2.05 ± 0.77 mg/day and 2.09 ± 0.70 mg/day, respectively. CYP2C9 and VKORC1 genetic variants as well as non-genetic factors such as age, body weight and body height account for 15.4% of variance in warfarin dose among our study population. Additional analysis of this combination could allow for personalized warfarin treatment in ethnic Indonesians.

  8. Genetics-based pediatric warfarin dosage regimen derived using pharmacometric bridging.

    Science.gov (United States)

    Lala, Mallika; Burckart, Gilbert J; Takao, Cheryl M; Pravica, Vera; Momper, Jeremiah D; Gobburu, Jogarao V S

    2013-07-01

    Warfarin dosage regimens using CYP2C9 and VKORC1 polymorphisms have been extensively studied in adults and is included in US Food and Drug Administration-approved warfarin labeling. However, no dosage algorithm is available for pediatric patients. To derive a genetics-based pediatric dosge regimen for warfarin, including starting dose and titration scheme. A model-based approach was developed based on a previously validated warfarin dosage model in adults, with subsequent comparison to pediatric data from pediatric warfarin dose, genotyping, and international normalized ratio (INR) results. The adult model was based on a previously established model from the CROWN (CReating an Optimal Warfarin dosing Nomogram) trial. Pediatric warfarin data were obtained from a study conducted at the Children's Hospital of Los Angeles with 26 subjects. Variant alleles of CYP2C9 (rs1799853 or *2, and rs1057910 or *3) and the VKORC1 single nucleotide polymorphism (SNP) rs9923231 (-1639 G>A) were assessed, where the rs numbers are reference SNP identification tags assigned by the National Center for Biotechnology Information. A pediatric warfarin model was derived using the previously validated model and clinical pharmacology considerations. The model was validated, and clinical trial simulation and stochastic modeling were used to optimize pediatric dosage and titration. The final dosage regimen was optimized based on simulations targeting a high (≥60%) proportion of INRs within the therapeutic range by week 2 of warfarin therapy while minimizing INRs >3.5 or A) genotypes may offer improved dosage compared to current treatment strategies, especially in patients with variant CYP2C9 and VKORC1 alleles. This pilot study provides the foundation for a larger prospective evaluation of genetics-based warfarin dosage in pediatric patients.

  9. Vitamin K intake and sensitivity to warfarin in patients consuming regular diets.

    Science.gov (United States)

    Lubetsky, A; Dekel-Stern, E; Chetrit, A; Lubin, F; Halkin, H

    1999-03-01

    The effect of dietary vitamin K intake on warfarin sensitivity is known only from case reports and few small clinical studies. We followed 50 patients commencing warfarin and consuming their regular diets (for 8 weeks) to study this relationship. A one-week recall dietary questionnaire was completed at weeks 2 and 8. Daily intake of nutrients and vitamin K was calculated from standard tables. Warfarin sensitivity index (WSI) was defined as final INR/final warfarin dose (mg/day/m2 of body surface area) (week 8). Vitamin K intake was 17-974 (median: 179) microg/day. Median WSI was 0.82 (0.31-4.47). A WSI value of 1.1 significantly separated excess (>250 microg/day) from normal (warfarin to achieve INR > or =2.0 (32.0+/-9.2 mg vs. 25.4+/-6.4 mg, p = 0.009) and required a higher maintenance steady state warfarin dose (5.7+/-1.7 mg/day vs. 3.5+/-1.0 mg/day, p warfarin is decreased by vitamin K intake > or =250 microg/day.

  10. White blood cells contribute to patient-specific warfarin dose for Han Chinese

    Institute of Scientific and Technical Information of China (English)

    ZHU Jin; ZHENG Wen-jie; ZHANG Wei-juan; WANG He-yao; WANG Chen

    2012-01-01

    Background Warfarin is the most commonly prescribed anticoagulant worldwide.Factors which influence warfarin's inter-individual requirements including age,weight,and genetic factors explained about 50% of dose variance,and unidentified factors still remain.The aim of this study was to explore whether white blood cell count affects warfarin dose requirements.Methods Three hundred and twenty-two patients suffering from venous thromboembolism (VTE) and taking warfarin were recruited in this study.Genotyping of selected genes was conducted and other information was collected using the Epidata software.Dosing algorithms were constructed by multivariate linear regression analyses.Results In addition to well-known factors such as age,body weight,CYP2Cg*3,and VKORC1 c.1173C>T,white blood cell counts negatively related to warfarin dose requirements and contributed to warfarin variability in Han Chinese by about 0.6%.Conclusion White blood cell count has a small but significant contribution to warfarin dose requirements in Han Chinese.

  11. Warfarin Dose Model for the Prediction of Stable Maintenance Dose in Indian Patients.

    Science.gov (United States)

    Gaikwad, Tejasvita; Ghosh, Kanjaksha; Avery, Peter; Kamali, Farhad; Shetty, Shrimati

    2017-01-01

    The main aim of this study was to screen various genetic and nongenetic factors that are known to alter warfarin response and to generate a model to predict stable warfarin maintenance dose for Indian patients. The study comprised of 300 warfarin-treated patients. Followed by extensive literature review, 10 single-nucleotide polymorphisms, that is, VKORC1-1639 G>A (rs9923231), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), FVII R353Q (rs6046), GGCX 12970 C>G (rs11676382), CALU c.*4A>G (rs1043550), EPHX1 c.337T>C (rs1051740), GGCX: c.214+597G>A (rs12714145), GGCX: 8016G>A (rs699664), and CYP4F2 V433M (rs2108622), and 5 nongenetic factors, that is, age, gender, smoking, alcoholism, and diet, were selected to find their association with warfarin response. The univariate analysis was carried out for 15 variables (10 genetic and 5 nongenetic). Five variables, that is, VKORC1-1639 G>A, CYP2C9*2, CYP2C9*3, age, and diet, were found to be significantly associated with warfarin response in univariate analysis. These 5 variables were entered in stepwise and multiple regression analysis to generate a prediction model for stable warfarin maintenance dose. The generated model scored R(2) of .67, which indicates that this model can explain 67% of warfarin dose variability. The generated model will help in prescribing more accurate warfarin maintenance dosing in Indian patients and will also help in minimizing warfarin-induced adverse drug reactions and a better quality of life in these patients.

  12. Effects of fesoterodine on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers.

    Science.gov (United States)

    Malhotra, Bimal; Alvey, Christine; Gong, Jason; Li, Xiaoxi; Duczynski, Gregory; Gandelman, Kuan

    2011-08-01

    Drug-drug interactions with warfarin are common with potentially harmful consequences. Preclinical in vitro studies suggest that fesoterodine or 5-hydroxymethyl tolterodine are not likely to affect warfarin metabolism, but a lack of interaction has not been demonstrated in a clinical study. This study shows that the pharmacokinetics and pharmacodynamics of warfarin 25 mg in healthy adults are unaffected by fesoterodine 8 mg, and that co-administration of warfarin 25 mg and fesoterodine 8 mg is safe and well tolerated. To confirm the lack of an interaction of fesoterodine 8 mg with warfarin pharmacokinetics and pharmacodynamics in healthy adults. In this open-label, two-treatment, crossover study, subjects (n= 14) aged 20-41 years with normal prothrombin time (PT) and International Normalized Ratio (INR) were randomized to receive a single dose of warfarin 25 mg alone in one period and fesoterodine 8 mg once daily on days 1-9 with a single dose of warfarin 25 mg co-administered on day 3 in the other period. There was a 10-day washout between treatments. Pharmacokinetic endpoints were area under the plasma concentration-time curve from time 0 to infinity (AUC(0,∞)), maximum plasma concentration (C(max)), AUC from time 0 to the time of the last quantifiable concentration (AUC(0,last)), time to C(max) (t(max) ), and half-life (t(1/2)) for S- and R-warfarin. Pharmacodynamic endpoints were area under the INR-time curve (AUC(INR) ), maximum INR (INR(max)), area under the PT-time curve (AUC(PT)) and maximum PT (PT(max)). Across all pharmacokinetic and pharmacodynamic comparisons, the point estimates of treatment ratio (warfarin co-administered with fesoterodine vs. warfarin alone) were 92-100%. The 90% confidence intervals for the ratios of the adjusted geometric means were contained within (80%, 125%). There were no clinically relevant changes in laboratory tests, vital signs or ECG recordings. The pharmacokinetics and pharmacodynamics of warfarin 25 mg in healthy

  13. Sonographic diagnosis of spontaneous intramural small bowel hematoma in a case of warfarin overdose.

    Science.gov (United States)

    Hou, Sheng-Wen; Chen, Chien-Chih; Chen, Kuo-Chih; Ko, Shih-Yu; Wong, Chung-Shun; Chong, Chee-Fah

    2008-01-01

    A 38-year-old man who had been treated with warfarin since mitral valve replacement 10 years earlier presented with acute onset of epigastralgia and melena. Coagulation tests were abnormal with a prolonged prothrombin time of >60 seconds and a prolonged activated partial thromboplastin time of >120 seconds. Abdominal sonographic examination revealed duodenal intramural hematoma that was confirmed on CT. Warfarin therapy was stopped and the patient was treated conservatively with vitamin K and fresh frozen plasma. Recovery was uneventful, and the patient was re-warfarinized 2 weeks later. Duodenal hematoma can be readily diagnosed with bedside sonography.

  14. Evaluation of Bleeding Events Requiring Hospitalization in Patients With Atrial Fibrillation Receiving Dabigatran, Warfarin, or Antiplatelet Therapy.

    Science.gov (United States)

    Riley, Tanya R; Gauthier-Lewis, Mary L; Sanchez, Chelsea K; Riley, Treavor T

    2017-04-01

    To determine the incidence and severity of bleeding events requiring hospitalization among patients with atrial fibrillation (AF) receiving anticoagulants (dabigatran or warfarin) or antiplatelet agents (eg, aspirin and clopidogrel). This was a single-center, retrospective cohort study involving 1494 patients with AF hospitalized from November 1, 2010, to November 1, 2011, with prior warfarin, dabigatran, or antiplatelet therapy. Overall bleeding events in the dabigatran group compared to the warfarin group were 24% and 12%, respectively ( P = .004). Of these events, individually, there were no significant differences in major (56% vs 58%, P = .88), life-threatening (25% vs 36%, P = .38), or minor bleeding (44% vs 42%, P = .06). Gastrointestinal (GI) bleeding occurred more in the dabigatran group compared to the warfarin group ( P = .02). Intracranial bleeding occurred in 15% of patients in the warfarin group and did not occur at all in the dabigatran group. Warfarin patients had significantly more overall bleeding events compared to antiplatelet therapy ( P bleeding ( P = .06). GI bleeding, however, favored the warfarin group over the antiplatelet group (48% vs 73%, P = .04). Anticoagulation with dabigatran was associated with an overall increased occurrence of bleeding requiring hospital admission compared to warfarin. GI bleeding was more prevalent with dabigatran and antiplatelets than with warfarin. There were more intracranial hemorrhages seen in the warfarin group.

  15. [EMERGENCY TREATMENT OF BLEEDING IN PATIENTS TAKING WARFARIN].

    Science.gov (United States)

    Prasolov, N V; Shulutko, E M; Bulanov, A Yu; Yatskov, K V; Shcherbakov, O V

    2015-01-01

    Anticoagulant therapy with vitamin K antagonists (AVK) is an effective treatment and prevention of thrombosis. One of the major disadvantages of the AVK is a risk for serious bleeding. Prothrombin complex concentrates (PCC), fresh frozen plasma (FFP) and vitamin K1 are available for control of these situations. The experience of special team ofthe Scientific Center for Hematology was the basis for presented retrospective study. Three regimens of warfarin-related bleeding were compared: PCC+ VK for several bleeding, FFP+ VK for different clinical situations and VKfor light bleeding. PCC showed himself as effective and safe hemostatic agent. Transfusions of FFP were sometimes not effective, sometimes led to TACO. Supplementation of vitamin K1 for patients of I and II groups provided more stable control of hemostasis. In III group VK vas effective to stop bleeding. Two impotent sings for conclusion: necessary of laboratory monitoring, TEG first of all; individual balance of hemostasis base of bleeding or thrombotic risks.

  16. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    Directory of Open Access Journals (Sweden)

    Varalaxmi Bhavani Nannaka

    2016-01-01

    Full Text Available Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses.

  17. Nurse driven protocol for head injured patients on warfarin.

    Science.gov (United States)

    Bair, Holly; Ivascu, Felicia; Janczyk, Randy; Nittis, Tara; Bendick, Philip; Howells, Greg

    2005-01-01

    The trauma quality improvement committee at our facility identified a significant number of patients on warfarin presenting to the emergency center after minor head trauma that subsequently expired from their intracranial hemorrhage prior to appropriate intervention. An analysis of this patient population identified multiple areas of delay. A collaborative effort between the emergency center nurses and the trauma service personnel resulted in a formal protocol to address each component of delay and expedite the process. Since implementation of this nursing driven protocol we have dramatically decreased the time to (1) Emergency Center Physician evaluation, (2) completion of head computerized tomography, (3) reversal of anticoagulation with fresh frozen plasma (FFP), and (4) most importantly, patient mortality rate. We conclude that this nursing driven protocol is effective in decreasing the mortality rate by eliminating diagnostic and therapeutic delays in this high-risk patient population.

  18. Monkey liver cytochrome P450 2C19 is involved in R- and S-warfarin 7-hydroxylation.

    Science.gov (United States)

    Hosoi, Yoshio; Uno, Yasuhiro; Murayama, Norie; Fujino, Hideki; Shukuya, Mitsunori; Iwasaki, Kazuhide; Shimizu, Makiko; Utoh, Masahiro; Yamazaki, Hiroshi

    2012-12-15

    Cynomolgus monkeys are widely used as primate models in preclinical studies. However, some differences are occasionally seen between monkeys and humans in the activities of cytochrome P450 enzymes. R- and S-warfarin are model substrates for stereoselective oxidation in humans. In this current research, the activities of monkey liver microsomes and 14 recombinantly expressed monkey cytochrome P450 enzymes were analyzed with respect to R- and S-warfarin 6- and 7-hydroxylation. Monkey liver microsomes efficiently mediated both R- and S-warfarin 7-hydroxylation, in contrast to human liver microsomes, which preferentially catalyzed S-warfarin 7-hydroxylation. R-Warfarin 7-hydroxylation activities in monkey liver microsomes were not inhibited by α-naphthoflavone or ketoconazole, and were roughly correlated with P450 2C19 levels and flurbiprofen 4-hydroxylation activities in microsomes from 20 monkey livers. In contrast, S-warfarin 7-hydroxylation activities were not correlated with the four marker drug oxidation activities used. Among the 14 recombinantly expressed monkey P450 enzymes tested, P450 2C19 had the highest activities for R- and S-warfarin 7-hydroxylations. Monkey P450 3A4 and 3A5 slowly mediated R- and S-warfarin 6-hydroxylations. Kinetic analysis revealed that monkey P450 2C19 had high V(max) and low K(m) values for R-warfarin 7-hydroxylation, comparable to those for monkey liver microsomes. Monkey P450 2C19 also mediated S-warfarin 7-hydroxylation with V(max) and V(max)/K(m) values comparable to those for recombinant human P450 2C9. R-warfarin could dock favorably into monkey P450 2C19 modeled. These results collectively suggest high activities for monkey liver P450 2C19 toward R- and S-warfarin 6- and 7-hydroxylation in contrast to the saturation kinetics of human P450 2C9-mediated S-warfarin 7-hydroxylation.

  19. Patient time requirements for anticoagulation therapy with warfarin.

    Science.gov (United States)

    Jonas, Daniel E; Bryant Shilliday, Betsy; Laundon, W Russell; Pignone, Michael

    2010-01-01

    Most patients receiving warfarin are managed in outpatient office settings or anticoagulation clinics that require frequent visits for monitoring. To measure the amount and value of time required of patients for chronic anticoagulation therapy with warfarin. /Participants. Prospective observation of a cohort of adult patients treated at a university-based anticoagulation program. Measurements. Participants completed a questionnaire and a prospective diary of the time required for 1 visit to the anticoagulation clinic, including travel, waiting, and the clinic visit. The authors reviewed subjects' medical records to obtain additional information, including the frequency of visits to the anticoagulation clinic. They used the human capital method to estimate the value of time. Eighty-five subjects completed the study. The mean (median) total time per visit was 147 minutes (123). Subjects averaged 15 visits per year (14) and spent 39.0 hours (29.3) per year on their visits. Other anticoagulation-related activities, such as communication with providers, pharmacy trips, and extra time preparing food, added an average of 52.7 hours (19.0) per year. The mean annual value of patient time spent traveling, waiting, and attending anticoagulation visits was $707 (median $591). The mean annual value when also including other anticoagulation-related activities was $1799 (median $1132). The time required of patients for anticoagulation visits was considerable, averaging approximately 2.5 hours per visit and almost 40 hours per year. for reducing patient time requirements, such as home-based testing, could reduce costs for patients, employers, and companions.

  20. Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures

    NARCIS (Netherlands)

    Garcia, D.; Alexander, J.H.; Wallentin, L.; Wojdyla, D.M.; Thomas, L.; Hanna, M.; Al-Khatib, S.M.; Dorian, P.; Ansell, J.; Commerford, P.; Flaker, G.; Lanas, F.; Vinereanu, D.; Xavier, D.; Hylek, E.M.; Held, C.; Verheugt, F.W.; Granger, C.B.; Lopes, R.D.

    2014-01-01

    Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted preprocedure, whether br

  1. Comparative evaluation of warfarin utilisation in two primary healthcare clinics in the Cape Town area

    OpenAIRE

    2013-01-01

    Background Although warfarin remains the anticoagulant drug of choice in a wide range of patients, its narrow therapeutic window makes patients susceptible to a high risk of bleeding complications or failure to prevent clotting. This has necessitated therapeutic monitoring in warfarinised patients. Factors that could be responsible for the fluctuating responses to warfarin vary from pharmacogenetic to concomitant morbidity, diet and medication. In order to assess the quality of management of ...

  2. Warfarin Accelerates Ectopic Mineralization in Abcc6−/− Mice: Clinical Relevance to Pseudoxanthoma Elasticum

    OpenAIRE

    2013-01-01

    Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. Warfarin, a commonly used anticoagulant, is associated with increased mineralization of the arterial blood vessels and cardiac valves. We hypothesized that warfarin may accelerate ectopic tissue mineralization in PXE, with clinical consequences. To test this hypothesis, we developed a model in which Abcc6−/− mice, which recapitulate features of PXE, were fed a diet supplement...

  3. Maintenance dose of warfarin in sheep and effect of diet: a preliminary report.

    Science.gov (United States)

    Sasaki, Takashi; Tsuda, Shoichi; Trujillo, Mario; Kirk Riemer, R; Reinhartz, Olaf

    2012-02-01

    Sheep models are widely used to evaluate the feasibility of various cardiac assist devices. Anticoagulation therapy postoperatively, however, is seldomly reported on. Continuous heparin infusion is often used, but is cumbersome due to long-term line management with the risk of infection and dislodgement. We contemplated using warfarin instead and started a pilot dose-finding study. Three sheep were given oral warfarin between 0.1 and 0.3 mg/kg/day. Prothrombin time was monitored and INR was calculated daily. If the INR did not reach a target of 2.5-3.5, warfarin dose was doubled. We found that sheep required a dose of warfarin between 1.6 and 2.4 mg/kg/day to raise the INR to the target zone. In a subsequent study to evaluate the effect of diet on INR in sheep, three sheep were fed alfalfa hay or alfalfa pellets in a crossover design. All the animals were given warfarin at the dose of 1.6 mg/kg. The diet was switched when the INR reached the target zone of 2.5-3.5. Hay-fed animals reached the target INR on days 6 and 7. On the other hand, pellet-fed animals did not reach the target value by day 7 with the initial dose and required 2.4 mg/kg of warfarin to achieve the goal. Hay raised the INR faster and higher than pellets with the same warfarin dose. Hay may be advantageous when using oral warfarin therapy in sheep.

  4. AREDS Formula, Warfarin, and Bleeding: A Case Report from the Michigan Anticoagulation Quality Improvement Initiative

    Science.gov (United States)

    Heidt, Steven T.; Haymart, Brian; Froehlich, James B.; Kline-Rogers, Eva; Barnes, Geoffrey D.

    2014-01-01

    Importance. The anticoagulant warfarin has been shown to interact with other medications, vitamin K containing foods, and over-the-counter products. These interactions may inhibit or potentiate the effect of warfarin, resulting in serious clotting or bleeding events. Observations. We report the case of an 84-year-old woman with atrial fibrillation, prescribed warfarin in May 2010 for stroke prevention. Her international normalized ratio (INR) was stable until April 2013, when she was prescribed AREDS (Age Related Eye Disease Study) formula pills, an eye vitamin compound, to slow the progression of age-related macular degeneration. This change was not reported to the Anticoagulation Service. Eighteen days later, she presented to the ED with groin and back pain and an INR of 10.4. An abdominal CT revealed a retroperitoneal hemorrhage with extension in multiple muscles. Both warfarin and AREDS were discontinued and the patient was discharged to subacute rehabilitation. This case was reviewed by the Anticoagulation Service and actions were taken to prevent similar adverse events. Conclusions. This report provides an example of the potential danger of supplement use, in this case, AREDS formula, in patients prescribed warfarin, and the importance of communicating medication changes to the providers responsible for warfarin management. PMID:25250052

  5. Service improvement system to enhance the safety of patients admitted on long-term warfarin.

    Science.gov (United States)

    Warcel, Dana; Johnson, Daniel; Shah, Neeraj; Shreeve, Norman

    2014-01-01

    It is common for hospital inpatients on warfarin to suffer from fluctuations in their INR (international normalised ratio). Raised INRs are potentially very dangerous and may result in acute life-threatening haemorrhages. Conversely, low INRs may increase the risk for the development of venous thromboembolism. Having observed many deranged INRs among hospital inpatients, we decided to focus our project on identifying the contributing factors to deranged INRs and ways to address this problem. We analysed the warfarin prescriptions on all drug charts and surveyed the junior doctor staff. Our results revealed poor knowledge and confidence levels on warfarin prescribing among junior doctor staff. This is likely to be reflected in the poor completion rate of warfarin prescriptions. We instituted practical changes to resolve the issue: most importantly, a change to the warfarin administration time from 6 pm to 2 pm, supported by a poster campaign to increase awareness of the problem. The objective of these changes was to reduce prescribing errors by reducing warfarin prescriptions out-of-hours, by the on-call doctors. We repeated the audit cycle twice. Although our interventions were successfully introduced as shown in our second audit cycle, the changes that were implemented were not sustained as shown in the third audit cycle. We identified a need for annual intervention to educate new junior doctor staff to ensure that the positive outcomes achieved are maintained in the long term.

  6. [Glucosamine and chondroitin sulfate do not enhance anticoagulation activity of warfarin in mice in vivo].

    Science.gov (United States)

    Yokotani, Kaori; Nakanishi, Tomoko; Chiba, Tsuyoshi; Sato, Yoko; Umegaki, Keizo

    2014-01-01

    As an adverse event, it has been reported that anticoagulation activity of warfarin was enhanced by simultaneous intakes of glucosamine and chondroitin sulfate. However, it is unclear whether these is a causative relation. Therefore, in the present study, we evaluated whether glucosamine and chondroitin sulfate enhanced the anticoagulant action of warfarin in mice in vivo, focusing on hepatic cytochrome P450 (CYPs)-mediated mechanisms. Mice were fed a diet containing various doses of glucosamine or chondroitin sulfate (0, 0.3, 1% (w/w)) for 2 weeks, and given warfarin by gavage on the last 2 days of the treatment regimen. Doses of glucosamine and chondroitin sulfate were 443 mg/kg and 464 mg/kg in the 0.3% diet groups, and 1523 mg/kg and 1546 mg/kg in the 1% diet groups. We found that 1% glucosamine significantly shortened prothrombin time and thrombotest Owen in animals given warfarin. However, the two ingredients did not induce or inhibit hepatic CYPs, including (S)-warfarin hydroxylase. These findings suggest that glucosamine and chondroitin sulfate do not affect the anticoagulation activity of warfarin through hepatic CYP mediated-mechanisms.

  7. Adherence to guidelines for avoiding drug interactions associated with warfarin--a Nationwide Swedish Register Study.

    Directory of Open Access Journals (Sweden)

    Jonatan D Lindh

    Full Text Available PURPOSE: To investigate the extent to which clinicians avoid well-established drug-drug interactions associated with warfarin. We hypothesised that clinicians would avoid combining non-steroidal anti-inflammatory drugs (NSAIDs, tramadol and sulfamethoxazole with warfarin. METHODS: A cross-sectional analysis of nationwide dispensing data was performed in Swedish individuals 18 years or older (n =  7,563,649. Odds ratios of interacting NSAIDs, tramadol and sulfamethoxazole versus respective prevalence of comparator drugs codeine, and ciprofloxacin in patients co-dispensed interacting warfarin versus patients unexposed was calculated. RESULTS: The odds of receiving an interacting NSAID versus the comparator codeine was markedly lower in patients with warfarin than in the remaining population (adjusted OR 0.21; 95% CI 0.20 - 0.22. Also, the interacting drugs tramadol and sulfamethoxazole were less common among patients dispensed warfarin as compared to the remaining population, although the decrease was much more modest (adjusted OR 0.83; CI 0.80-0.87 and 0.81; CI 0.73 - 0.90. CONCLUSIONS: In conclusion, Swedish doctors in the vast majority of cases refrain from prescribing NSAIDs to patients already on warfarin. Tramadol and sulfamethoxazole are however rarely avoided.

  8. Molecular displacement of warfarin from human serum albumin by flavonoid aglycones

    Energy Technology Data Exchange (ETDEWEB)

    Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Pécs H-7624 (Hungary); Li, Yin; Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, H-7624 Pécs (Hungary); Petrik, József [Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb (Croatia); Vladimir-Knežević, Sanda [Department of Pharmacognosy, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb (Croatia); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Pécs H-7624 (Hungary)

    2013-10-15

    The well-known 4-hydroxycoumarin derivative warfarin is a widespread anticoagulant drug. Besides its strong albumin binding property warfarin has a narrow therapeutic window. Therefore, a few percent of displacement from albumin can result in serious biological consequences. The flavonoid molecular group also shows very strong plasma albumin binding characteristics occupying the same binding site. It is plausible to hypothesize that flavonoid aglycones may be able to displace warfarin from human serum albumin (HSA). In our study the competing activities of different flavone (acacetin, apigenin, chrysin, luteolin), flavonol (galangin, quercetin) and flavanone (hesperetin, naringenin) aglycones were investigated using fluorescence spectroscopy. Our results represent that flavonoids are able to displace warfarin from the surface of HSA. On the other hand, when comparing flavone or flavonol groups to flavanones the latter group seems to be much weaker competitor. These observations were also supported by calculation of stability constants. Our investigations strongly suggest that we should reckon with the described molecular displacement. However, further in vivo studies are needed to support the findings of our model system. -- Highlights: • Various flavonoids are able to displace warfarin from human serum albumin. • Flavones and flavonols are much more effective competitors than flavanones. • Even 300 nM aglycone concentrations show the interaction with 3 μM warfarin. • Flavonoid pairs show quasi-additive desorbing property. • Flavones and flavonols are much stronger competitors than the examined drugs.

  9. AREDS Formula, Warfarin, and Bleeding: A Case Report from the Michigan Anticoagulation Quality Improvement Initiative

    Directory of Open Access Journals (Sweden)

    Eric Puroll

    2014-01-01

    Full Text Available Importance. The anticoagulant warfarin has been shown to interact with other medications, vitamin K containing foods, and over-the-counter products. These interactions may inhibit or potentiate the effect of warfarin, resulting in serious clotting or bleeding events. Observations. We report the case of an 84-year-old woman with atrial fibrillation, prescribed warfarin in May 2010 for stroke prevention. Her international normalized ratio (INR was stable until April 2013, when she was prescribed AREDS (Age Related Eye Disease Study formula pills, an eye vitamin compound, to slow the progression of age-related macular degeneration. This change was not reported to the Anticoagulation Service. Eighteen days later, she presented to the ED with groin and back pain and an INR of 10.4. An abdominal CT revealed a retroperitoneal hemorrhage with extension in multiple muscles. Both warfarin and AREDS were discontinued and the patient was discharged to subacute rehabilitation. This case was reviewed by the Anticoagulation Service and actions were taken to prevent similar adverse events. Conclusions. This report provides an example of the potential danger of supplement use, in this case, AREDS formula, in patients prescribed warfarin, and the importance of communicating medication changes to the providers responsible for warfarin management.

  10. Pharmacogenetics and anticoagulant therapy: two cases of genetically determined response to warfarin.

    Science.gov (United States)

    Cortez-Dias, Nuno; Correia, Maria José; Coutinho, Ana; Fernandes, Catarina; Diogo, A Nunes; Lopes, Mário G

    2009-09-01

    Inter- and intra-individual variability of response to warfarin means that its anticoagulant effect must be monitored, given the risk of thromboembolic complications and bleeding. This variability is influenced by gender, age, body mass index, smoking, diet, comorbid conditions, drug interactions and genetic factors. Pharmacogenetics refers to the study of genetic background to predict drug response, effectiveness and risk of adverse effects in a given patient. The authors illustrate its relevance in two case reports. A 40-year-old woman admitted for massive pulmonary thromboembolism underwent anticoagulant and fibrinolytic therapy, following which warfarin was needed in unusually high doses to achieve effective anticoagulation. The genetic variants c.430CC and c.1075AA of the CYP2C9 gene were identified, predisposing to rapid warfarin metabolism, as well as the c.-1639GG variant of the VKORC1 gene, associated with low sensitivity to the drug. Together, these variants give high resistance to warfarin. In the second case, a 76-year-old man with permanent atrial fibrillation developed excessive prolongation of prothrombin time after being treated with 5 mg/day warfarin for 5 days. The genetic variants c.430CC and c.1075AC of the CYP2C9 gene and 1639AA of the VKORC1 gene were identified. Together, these polymorphisms confer high sensitivity to warfarin, necessitating smaller doses to maintain therapeutic anticoagulation levels. The authors review the relevance of the study of genetic polymorphisms related to anticoagulant therapy and discuss its potential usefulness in clinical practice.

  11. Warfarin Management Pathway: A clear and safe algorithm, from admission to discharge.

    Science.gov (United States)

    Hart-George, Alice

    2014-01-01

    Warfarin is the most commonly prescribed anticoagulant in the UK and the one most frequently associated with both fatal medication errors and litigation claims [1]. Its life-threatening interactions and side effects are a concern for all doctors. Identifying and implementing solutions to achieve safer prescribing and monitoring is imperative to improve patient safety. The National Patient Safety Agency (NPSA) has outlined the major risks associated with anticoagulant therapy and sought to establish safer practice [1]. The monitoring of safety indicators has been highlighted as a solution. This quality improvement project (QIP) introduces a management algorithm for oral anticoagulant therapy in hospital patients, validated through a completed audit cycle. It was completed at one district general hospital (DGH) in England and involved all inpatient wards. Doctors and pharmacists were interviewed to assess their knowledge of the correct pathways for management of patients on warfarin. The number of errors on hospital warfarin charts was audited over three weeks. These results, coupled with senior haematological advice led to the production of an algorithm illustrating the gold-standard pathway for warfarin management from admission to discharge. It was emailed to all doctors in the Trust and a laminated copy attached to hospital Pneumatic Tube System (PTS) machines. The warfarin charts were re-audited over the following three weeks. The results showed a marked decrease in errors and incomplete anticoagulation referrals as well as a reduction in doctors' anxiety around prescribing warfarin.

  12. Enzyme-catalyzed Michael addition for the synthesis of warfarin and its determination via fluorescence quenching of L-tryptophan

    Science.gov (United States)

    Yuan, Yusheng; Yang, Liu; Liu, Shaopu; Yang, Jidong; Zhang, Hui; Yan, Jingjing; Hu, Xiaoli

    2017-04-01

    A sensitive fluorescence sensor for warfarin was proposed via quenching the fluorescence of L-tryptophan due to the interaction between warfarin and L-tryptophan. Warfarin, as one of the most effective anticoagulants, was designed and synthesized via lipase from porcine pancreas (PPL) as a biocatalyst to catalyze the Michael addition of 4-hydroxycoumarin to α, β-unsaturated enones in organic medium in the presence of water. Furthermore, the spectrofluorometry was used to detect the concentration of warfarin with a linear range and detection limit (3σ/k) of 0.04-12.0 μmol L- 1 (R2 = 0.994) and 0.01 μmol L- 1, respectively. Herein, this was the first application of bio-catalytic synthesis and fluorescence for the determination of warfarin. The proposed method was applied to determine warfarin of the drug in tablets with satisfactory results.

  13. Warfarin-induced artery calcification is accelerated by growth and vitamin D.

    Science.gov (United States)

    Price, P A; Faus, S A; Williamson, M K

    2000-02-01

    The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to

  14. Warfarin reversal emerging as the major indication for fresh frozen plasma use at a tertiary care hospital.

    Science.gov (United States)

    Ozgonenel, Bulent; O'Malley, Barbara; Krishen, Priya; Eisenbrey, A B

    2007-12-01

    Because of the increase in the use of warfarin in the population in recent years, reversal of warfarin-related coagulopathy has become common in daily hospital practice. Transfusion of fresh frozen plasma (FFP) is the preferred treatment method for urgent warfarin reversal in the USA. We have undertaken a 1-month audit of FFP usage to ascertain the impact of warfarin use on the consumption of FFP. Sixty percent of the 376 units of FFP that were transfused during the study month were used to reverse warfarin effects. The most common reason to reverse warfarin was bleeding. Thirty-three percent of the units were used for the treatment of other coagulopathies, 7% were used in therapeutic plasmapheresis, and banks of hospitals serving a predominantly elderly patient population should anticipate a higher consumption of FFP. Careful monitoring of warfarin therapy, stringent implementation of the warfarin reversal guidelines, and the introduction of newer products for warfarin reversal would help reduce the consumption of FFP.

  15. Lack of clinical pharmacodynamic and pharmacokinetic drug-drug interactions between warfarin and the antisense oligonucleotide mipomersen.

    Science.gov (United States)

    Li, Zhaoyang; Hard, Marjie L; Grundy, John S; Singh, Tejdip; von Moltke, Lisa L; Boltje, Ingrid

    2014-08-01

    Mipomersen is a second-generation antisense oligonucleotide indicated as an adjunct therapy for homozygous familial hypercholesterolemia (HoFH). Warfarin is commonly prescribed for a variety of cardiac disorders in homozygous familial hypercholesterolemia population, and concurrent use of warfarin and mipomersen is likely. This open-label, single-sequence 2-period phase 1 study in healthy subjects evaluated the potential drug-drug interactions between mipomersen and warfarin. The subjects received a single oral 25 mg dose of warfarin alone on day 1, and after a 7-day washout period, received 200 mg mipomersen alone subcutaneously every other day on days 8-12, and received both concurrently on day 14. Coadministration of mipomersen did not change the pharmacodynamics (international normalized ratio, prothrombin time, and activated partial thromboplastin time) and pharmacokinetics (PK) of warfarin. There were no clinically significant changes in the PK of mipomersen with concurrent administration of warfarin. There were no events indicative of an increase in bleeding tendency when warfarin was coadministered with mipomersen, and the adverse event profile of mipomersen did not appear to be altered in combination with warfarin, as compared with that of the respective reference treatment. The combination of these 2 medications appeared to be safe and well tolerated. These results suggest that the dosage adjustment of warfarin or mipomersen is not expected to be necessary with coadministration.

  16. Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in "real-world" clinical practice

    DEFF Research Database (Denmark)

    Li, Xiaoyan; Deitelzweig, Steve; Keshishian, Allison

    2017-01-01

    ) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate...... to warfarin treatment. This is the largest "real-world" study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various...

  17. Correlation between single nucleotide polymorphisms in CYP4F2 and warfarin dosing in chinese valve replacement patients

    Directory of Open Access Journals (Sweden)

    Li Jie-Hui

    2012-09-01

    Full Text Available Abstract Background Individuals with implanted mechanical valve prostheses require lifelong anticoagulation therapy with warfarin. The narrow therapeutic index of warfarin makes it difficult to dose and maintain proper anticoagulation. A number of single nucleotide polymorphisms (SNPs affecting vitamin K or warfarin metabolism have been shown to affect warfarin dosing. Our aim was to study the effect of the CYP4F2 rs2108622-1347 (C > T variant on warfarin dosing in Chinese patients. Methods We studied 352 patients after heart valve replacement surgery. Warfarin dosing for patients was adjusted to achieve 1.8 ≤ INR ≤ 2.5. We determined the presence of SNPs in CYP4F2 in these patients and investigated their association with warfarin dosing. Results We found the frequency of the CYP4F2 rs2108622 C allele was 79.5% and T-allele frequency was 20.5%. The warfarin dose requirement for CC individuals was significantly lower than that for CT or TT individuals (P  Conclusions This study demonstrates that CYP4F2 rs2108622 significantly affects the warfarin dose requirement to achieve adequate anticoagulant activity in Chinese individuals. Genotyping of this SNP may allow clinicians to determine the initiation dose for patients following valve-replacement surgery in China.

  18. Prevalence of Warfarin Genotype Polymorphisms in Patients with Mechanical Circulatory Support.

    Science.gov (United States)

    Awad, Morcos; Czer, Lawrence S C; Soliman, Camelia; Mirocha, James; Ruzza, Andrea; Pinzas, Joshua; Rihbany, Kelsey; Chang, David; Moriguchi, Jaime; Ramzy, Danny; Esmailian, Fardad; Kobashigawa, Jon; Arabia, Francisco

    2015-01-01

    Polymorphisms for VKORC1 and CYP2C9 are associated with increased warfarin sensitivity. The prevalence of these polymorphisms in patients with mechanical circulatory support (MCS) is unknown. Polymorphisms for VKORC1 and CYP2C9 were determined in 65 patients undergoing MCS surgery. Postoperative warfarin dose, international normalized ratio (INR), and bleeding events were measured until discharge, 6 months, or composite end point (in-hospital MCS recovery, heart transplant, or death). A total of 67.7% (44/65) had at least one polymorphism: VKORC1 (44.6%), CYP2C9*2 (7.7%), CYP2C9*3 (4.6%), CYP2C9*2 and VKORC1 (3.1%), or CYP2C9*3 and VKORC1 (7.7%). At discharge or before composite end point, patients with any polymorphism received a lower mean warfarin dosage than patients having no polymorphism (3.21 ± 1.47 vs. 5.57 ± 3.72 mg, p = 0.015) and achieved a similar mean INR (2.20 ± 0.67 vs. 2.19 ± 0.69, p = 0.96). There was no significant difference in bleeding rates within 6 months or before composite end point (6.13 vs. 8.02 events/patient-year, p = 0.13). One or more polymorphisms for VKORC1 or CYP2C9 (associated with warfarin sensitivity) were found in 67.7% of MCS patients. By using a warfarin genotype-guided approach, MCS patients with polymorphisms received a lower warfarin dosage to achieve a similar INR, with similar bleeding rates, in comparison with no polymorphisms. A warfarin genotype-guided approach avoided excessive anticoagulation and its attendant bleeding risks.

  19. Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy.

    Science.gov (United States)

    Takada, Hiroaki; Toru, Hifumi; Bunya, Naofumi; Kiriu, Nobuaki; Kato, Hiroshi; Koido, Yuichi; Yasuhiro, Kuroda

    2014-06-01

    We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient’s serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.

  20. Measurement of warfarin in the oral fluid of patients undergoing anticoagulant oral therapy.

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    Silvia Ghimenti

    Full Text Available BACKGROUND: Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls. METHODOLOGY: A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm. FINDINGS: The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL. Dosage was not correlated to INR (r = -0.03, p = 0.85 but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006. The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009 confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004. CONCLUSIONS: Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters.

  1. Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin-A Nationwide Cohort Study.

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    Jannik Langtved Pallisgaard

    Full Text Available Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy.Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456, and 63% in the warfarin group (n = 774. Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5 and 6.9 (IQR 3.9 to 12.1 weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1 in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42. Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08.Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.

  2. Impact of Body Mass Index and Genetics on Warfarin Major Bleeding Outcomes in a Community Setting.

    Science.gov (United States)

    Hart, Ragan; Veenstra, David L; Boudreau, Denise M; Roth, Joshua A

    2017-02-01

    Several studies have demonstrated an association between body mass index (BMI) and warfarin therapeutic dose, but none evaluated the association of BMI with the clinically important outcome of major bleeding in a community setting. To address this evidence gap, we conducted a case-control study to evaluate the association between BMI and major bleeding risk among patients receiving warfarin. We used a case-control study design to evaluate the association between obesity (BMI >30.0 kg/m(2)) and major bleeding risk among 265 cases and 305 controls receiving warfarin at Group Health, an integrated healthcare system in Washington State. Multivariate logistic regression was used to adjust for potential confounders derived from health plan records and a self-report survey. In exploratory analyses we evaluated the interaction between genetic variants potentially associated with warfarin bleeding (CYP2C9, VKORC1, and CYP4F2) and obesity on the risk of major bleeding. Overall, the sample was 55% male, 94% Caucasian, and mean age was 70 years. Cases and controls had an average of 3.4 and 3.7 years of warfarin use, respectively. Obese patients had significantly lower major bleeding risk relative to non-obese patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.92). The OR was 0.56 (95% CI 0.35-0.90) in patients with ≥1 year of warfarin use, and 0.78 (95% CI 0.40-1.54) in patients with bleeding among those wild type for CYP4F2*3, but not among variants. Our findings suggest that BMI is an important clinical factor in assessing and managing warfarin therapy. Future studies should confirm the major bleeding associations, including the interaction between obesity and CYP4F2*3 status identified in this study, and evaluate potential mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Synthesis of deuterium labelled metabolites of warfarin and phenprocoumon

    Energy Technology Data Exchange (ETDEWEB)

    Heimark, L.D.; Toon, S.; Low, L.K.; Swinney, D.C.; Trager, W.F.

    1986-02-01

    The synthesis of deuterium labelled 4'-,6-,7- and 8-hydroxy metabolites of warfarin and phenprocoumon is described. The pentadeuterio labelled 6-,7- and 8-hydroxyphenprocoumons were prepared via alkylation of the respective 6-, 7- and 8-methoxy-4-hydroxycoumarins with 1-(phenyl-d/sub 5/)-1-bromopropane and subsequent cleavage of the methyl protecting group with boron tribromide. The synthesis of 1-(pentadeuteriophenyl)-1-bromopropane and the 6-, 7-and 8-methoxy-4-hydroxycoumarins are also presented. The pentadeuterio labelled 6-, 7- and 8-hydroxywarfarins were obtained by reaction of 4-(phenyl-d/sub 5/)-3-buten-2-one with the respective 6-, 7- and 8-hydroxy-4-hydroxycoumarins in methanol followed by hydrolysis of the intermediate cyclic methyl ketals in aqueous acid. 4-Hydroxycoumarin-5,6,7,8-d/sub 4/, prepared from phenyl-d/sub 6/ and tetradeuteriomalonic acid, was reacted with 1-(p-hydroxyphenyl)-1-propanol and 4-(p-hydroxyphenyl)-3-buten-2-one to yield labelled 4'-hydroxyphenprocoumon and 4'-hydroxywarfarin respectively.

  4. Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

    Science.gov (United States)

    Janzic, Andrej; Kos, Mitja

    2015-04-01

    Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

  5. Cost-effectiveness of apixaban versus warfarin and aspirin in Sweden for stroke prevention in patients with atrial fibrillation.

    Science.gov (United States)

    Lanitis, Tereza; Kongnakorn, Thitima; Jacobson, Lena; De Geer, Anna

    2014-08-01

    Atrial fibrillation (AF), one of the major risk factors for stroke, imposing a substantial burden to the Swedish health care system. Apixaban has demonstrated superiority to warfarin and aspirin in stroke prevention amongst patients with AF in two large randomised clinical trials. The aim of this study was to assess the economic implications of apixaban against warfarin and aspirin in these patients from a Swedish societal perspective. A Markov cohort model was constructed to characterise the consequences of anticoagulant treatment with regards to thromboembolic and bleeding events, as well as the associated health care costs, life-years and quality-adjusted life years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin. Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban relative to warfarin (among patients suitable for warfarin treatment) and aspirin (among patients unsuitable for warfarin treatment) were calculated. Costs (in 2011 SEKs) and QALYs were discounted at 3% per annum. The model estimated the ICER of apixaban versus warfarin amongst patients who are suitable for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal treatment option compared with warfarin and aspirin, when the willingness-to-pay is above SEK 35,000 and SEK 45,000 per QALY, respectively. Apixaban was found to be a cost-effective alternative to warfarin and aspirin for stroke prevention in patients with AF in Sweden. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Educating patients about warfarin therapy using information technology: A survey on healthcare professionals’ perspectives

    Directory of Open Access Journals (Sweden)

    Mullan J

    2012-06-01

    Full Text Available Objective: To explore healthcare professionals’ views about the benefits and challenges of using information technology (IT resources for educating patients about their warfarin therapy.Methods: A cross-sectional survey of both community and hospital-based healthcare professionals (e.g., doctors, pharmacists and nurses involved using a purpose-designed questionnaire. The questionnaires were distributed using a multi-modal approach to maximise response rates.Results: Of the total 300 questionnaires distributed, 109 completed surveys were received (43.3% response rate. Over half (53.2% of the healthcare participants were aged between 40-59 years, the majority (59.5% of whom were female. Fifty nine (54.1% participants reported having had no access to warfarin-specific IT-based patient education resources, and a further 19 (38.0% of the participants who had IT-access reported that they never used such resources. According to the healthcare participants, the main challenges associated with educating their patients about warfarin therapy included: patient-related factors, such as older age, language barriers, cognitive impairments and/or ethnic backgrounds or healthcare professional factors, such as time constraints. The healthcare professionals reported that there were several aspects about warfarin therapy which they found difficult to educate their patients about which is why they identified computers and interactive touch screen kiosks as preferred IT devices to deliver warfarin education resources in general practices, hospital-based clinics and community pharmacies. At the same time, the healthcare professionals also identified a number of facilitators (e.g., to reinforce warfarin education, to offer reliable and easily comprehensible information and barriers (e.g., time and costs of using IT resources, difficulty in operating the resources that could impact on the effective implementation of these devices in educating patients about their

  7. The effects of ferulic acid on the pharmacokinetics of warfarin in rats after biliary drainage

    Directory of Open Access Journals (Sweden)

    Li H

    2016-07-01

    Full Text Available Haigang Li,1,2 Yang Wang,1 Rong Fan,1 Huiying Lv,3 Hua Sun,4 Haitang Xie,4 Tao Tang,1 Jiekun Luo,1 Zian Xia1 1Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, 2Department of Pharmacy, Changsha Medical University, 3Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, 4Anhui Provincial Centre for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China Abstract: According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN: healthy rats after the administration of warfarin sodium, Group 2 (WO: a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN: healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO: a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography–tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0–t and peak plasma concentration (Cmax, respectively, whereas time to Cmax (Tmax was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO

  8. Comparison of benefit between dabigatran and warfarin among patients with atrial fibrillation: A systematic review

    Directory of Open Access Journals (Sweden)

    Amal K Sulieman

    2016-01-01

    Full Text Available Warfarin is recognized as the standard antithrombotic agent for stroke prevention. However, new oral anticoagulant such as dabigatran constitutes huge improvement to compensate for the limitation of warfarin. A literature review was performed to compare and contrast the overall benefit of dabigatran and warfarin among patients with atrial fibrillation. We utilized HighWire as the data source for randomized controlled trials based on inclusion and exclusion criteria (from January 2007 to September 2013. Descriptive and quantitative information related to stroke and major bleeding were extracted from each trial. After a comprehensive screening of 298 search results, 17 studies which enrolled a total of 127,594 patients were included. Warfarin was found to have higher mean event rates for incidence of stroke, major bleeding, and net clinical benefit compared to dabigatran 110 mg and dabigatran 150 mg. Dabigatran 110 mg has higher rate of stroke and net clinical benefit than dabigatran 150 mg with less major hemorrhage. Overall, dabigatran had higher efficacy and safety profile than warfarin. Further research is required to determine the clinical feasibility of dabigatran in real-life practice.

  9. Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

    Science.gov (United States)

    Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

    2016-11-01

    All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

  10. Effects of Tramadol Coadministration on Prothrombin Time-International Normalized Ratio in Patients Receiving Warfarin.

    Science.gov (United States)

    Hosono, Tomomi; Kondo, Aiko; Kambayashi, Yasuyuki; Homma, Masato

    2017-01-01

     Several case studies have reported a possible drug interaction between warfarin and tramadol where tramadol coadministration enhanced the antithrombotic effects of warfarin. To assess this drug interaction, changes in prothrombin time-international normalized ratio (PT-INR) before and after tramadol coadministration were investigated in patients receiving warfarin. For this study, we examined 54 patients (male/female: 22/32, 68.4±12.7 years) who were being treated with warfarin for deep vein thrombosis, atrial fibrillation, arteriosclerosis obliterans, congestive heart failure, and other vascular diseases. Significant increases in PT-INR were observed 9.5 (1-118) d after coadministration of tramadol (1.81±0.56 vs. 2.47±1.10, ptramadol were compared with other groups of patients to find drug interaction risk factors. Logistic regression analysis revealed that lower levels of albumin (3.5 g/dL or less) [odds ratio (OR) 22.1; 95%CI 2.9-169.9]; lower eGFR (50 mL/min or less) (OR 7.7; 95%CI 1.4-42.0); and PT-INR before tramadol coadministration (OR 38.2; 95%CI 3.7-397.6) were characteristic of the PT-INR increased group. These results suggest that tramadol coadministration enhanced the antithrombotic effects of warfarin in patients with higher PT-INR, lower albumin levels and decreased renal function as the risk factors for this drug interaction.

  11. Psychometric properties of the 8-item Morisky Medication Adherence Scale in patients taking warfarin.

    Science.gov (United States)

    Wang, Ye; Kong, Ming Chai; Ko, Yu

    2012-10-01

    There is no patient-reported medication adherence measure that has been validated in Singapore. This study aimed to validate the 8-item Morisky Medication Adherence Scale (MMAS) in patients taking warfarin in Singapore. A cross-sectional survey was conducted in a convenience sample of 151 patients taking warfarin at an anticoagulation clinic in 2011. Respondents completed the MMAS in English or Chinese depending on their preference. The MMAS had a Cronbach's alpha of 0.56 and good criterion-related validity as the scale scores were associated with warfarin refill rates (p = 0.04). Respondents with higher MMAS scores were found to have a higher percentage of International Normalised Ratios (INRs) within the therapeutic range (p = 0.01), higher adherence to diet recommendations (p = 0.02), and less perceived difficulty in taking all medications (p warfarin at the same time every day (p warfarin. Future research is needed to investigate the scale's psychometric properties in other patient populations and clinical settings.

  12. Decreased warfarin effects in elder with recurrent Clostridium difficile infection during fidaxomicin therapy: a case report

    Directory of Open Access Journals (Sweden)

    Antonio Riccardo Buonuomo

    2015-03-01

    Full Text Available Clostridium difficile infection is a disease with increasing incidence, particularly in high‑riskpatients such as the elderly, immunocompromised patients, etc.We report an unexpected decrease of International Normalized Ratio (INR response to warfarin during a first recurrence of Clostridium difficile infection (CDI treated with fidaxomicin. The patient, an old man who has prosthetic heart valves on anticoagulation therapy with warfarin, was treated with an association of vancomycin plus metronidazole for a first episode of CDI. Patient remained symptom‑free for few days and then he presented with recurrent diarrhea. A retreatment with vancomycin and metronidazole didn’t resolve symptoms of CDI, therefore he underwent fidaxomicin treatment for 10 days, with rapid resolution of diarrhea. In the meantime, warfarin effects diminished, and only with increases of dosage INR therapeutic range was achieved few days after discontinuing fidaxomicin. According to product information, fidaxomicin doesn’t interfere with warfarin. The authors highlight the different plausible mechanisms to explain the association between the unexpected decreased effect of warfarin and factors that could have influenced such event. The frequent update of product information through good pharmacovigilance practices could help clinicians in the management of unexpected events.http://dx.doi.org/10.7175/cmi.v9i1.953

  13. Study of warfarin patients investigating attitudes toward therapy change (SWITCH Survey).

    Science.gov (United States)

    Attaya, Shariff; Bornstein, Tammi; Ronquillo, Nemencio; Volgman, Robert; Braun, Lynne T; Trohman, Richard; Volgman, Annabelle

    2012-11-01

    Although the oral anticoagulant warfarin has undoubtedly saved lives and reduced the number of strokes in patients with atrial fibrillation, it is a cumbersome medication to manage and take. Novel oral anticoagulants, such as dabigatran, offer therapeutic anticoagulation without requisite blood testing or dietary restrictions. We conducted a survey of the attitudes of patients enrolled in a warfarin clinic toward switching to a novel anticoagulant. From September to December 2010, a written survey was offered to 180 patients in the Warfarin Clinic of the Rush University Medical Center and 155 patients filled out the survey (86% response rate). Inclusion criteria included being 18 years of age or older, on warfarin for 2 months. Fifty-eight percent of patients were willing to switch anticoagulants. Women were significantly less willing to switch from warfarin than men (31 of 71, 44% vs. 54 of 78, 69%; P = 0.003). Patients older than 70 years were significantly more willing to switch anticoagulants than those younger than 70 years (48 of 68, 71% vs. 38 of 75, 51%; P = 0.017). There are significant differences across age and gender in the initial willingness of patients to accept novel anticoagulants. These differences may have important implications in the prevention and treatment of thromboembolic events.

  14. Warfarin dose requirement and cytochrome P450 2C9 and Vitamin K epoxide reductase complex subunit 1-1639 genetic polymorphisms in Thai patients

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    Burassakorn Subsuphan

    2016-01-01

    Conclusions: Using stepwise multiple linear regression, VKORC1-1639 AA, age, and weight could explain about 45.3% of the variation of warfarin maintenance dose. Multivariate analysis of the equation indicated a significant negative correlation between warfarin dose and VKORC1-1639 AA and age, but a significant positive correlation between warfarin dose and weight. This suggested that VKORC1 genotyping may be more important in warfarin dose adjustment and should be a priority for genotype measurement.

  15. A randomized trial of lottery-based incentives and reminders to improve warfarin adherence: the Warfarin Incentives (WIN2) Trial.

    Science.gov (United States)

    Kimmel, Stephen E; Troxel, Andrea B; French, Benjamin; Loewenstein, George; Doshi, Jalpa A; Hecht, Todd E H; Laskin, Mitchell; Brensinger, Colleen M; Meussner, Chris; Volpp, Kevin

    2016-11-01

    Previous research has suggested that daily lottery incentives could improve medication adherence. Such daily incentives include implicit reminders. However, the comparative effectiveness of reminders alone versus daily incentives has not been tested. A total of 270 patients on warfarin were enrolled in a four-arm, multi-center, randomized controlled trial comparing a daily lottery-based incentive, a daily reminder, and a combination of the two against a control group (usual care). Participants in the reminder group had the lowest percentage of time out of target international normalized ratio (INR) range, the primary outcome, with an adjusted odds of an out-of-range INR 36% lower than among those in the control group, 95%CI [7%, 55%]. No other group had a statistically significant improvement in anticoagulation control relative to the control group or to each other. The only group that had significant improvement in incorrect adherence was the lottery group (incorrect adherence: 12.1% compared with 23.7% in the control group, difference of -7.4% 95%CI [-14%, -0.3%]). However, there was no relationship between changes in adherence and anticoagulation control in the lottery group. Automated reminders led to the largest improvements in anticoagulation control, although without impacting measured adherence. Lottery-based reminders improved measured adherence but did not lead to improved anticoagulation control. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  16. CATCH: A randomized trial comparing tinzaparin versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients

    NARCIS (Netherlands)

    Lee, Agnes Y.; Bauersachs, Rupert; Janas, Mette S.; Jarner, Mikala F.; Kamphuisen, Pieter W.; Meyer, Guy; Paz-Ares, Luis; Khorana, Alok A.

    2012-01-01

    Background: VTE is a major cause of morbidity and mortality in cancer patients. LMWHs have been shown to be superior to warfarin in one randomized study, but adequately powered confirmatory studies have not been conducted and warfarin continues to be widely used for treatment of cancer-associated VT

  17. Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors?

    Science.gov (United States)

    Bala, Abiram; Huddleston, James I; Goodman, Stuart B; Maloney, William J; Amanatullah, Derek F

    2017-09-01

    There is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors. Using a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time? We queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes. All patients who had any form of antiplatelet or anticoagulation prescribed within 1 year before TKA were excluded from our study cohort. We then identified patients who had either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed within 2 weeks of primary TKA. Each cohort was matched by age and sex. Elixhauser comorbidities and Charlson Comorbidity Index for each group were calculated. We identified 1016 patients with aspirin, and age- and sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the understanding that patients at greater risk may have had more-attentive surveillance, the incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications (bleeding requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), postoperative anemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test was used to determine statistical significance. Utilization was calculated using compound annual growth rate. There was a difference in the incidence of DVT at 90 days (p < 0

  18. Upper airway obstruction by epiglottis and arytenoids hematoma in a patient treated with warfarin sodium.

    Science.gov (United States)

    Ikeda, Ryoukichi; Chiba, Toshihiko; Gorai, Shigeki; Kobayashi, Toshimitu

    2010-02-01

    With the increase in the number of patients undergoing warfarin therapy, reports of complications due to such therapy have become frequent. Although upper airway obstruction secondary to bleeding resulting from warfarin therapy is rare, it is a life-threatening complication because of the risk of airway obstruction. Only one previous case of hematoma of the epiglottis and arytenoids has been reported. We here in report a case of an 83-year-old woman on warfarin therapy who presented with a sore throat. On flexible nasoendoscopy, edema of the epiglottis and bilateral arytenoids with a red and purple hue were observed. The left true vocal cord was erythematous, but the airway was adequately maintained. The PT-INR of the patient was 10. She was managed conservatively and had a good course.

  19. Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole.

    Science.gov (United States)

    Powers, Anna; Loesch, Erin B; Weiland, Anthony; Fioravanti, Nicole; Lucius, David

    2017-07-01

    To evaluate the utility of a preemptive warfarin dose reduction at the time of initiation of either sulfamethoxazole-trimethoprim or metronidazole, a retrospective chart review of patients who received an outpatient prescription for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans who had a warfarin dose reduction and those who did not within 120 h (5 days) of antibiotic initiation. The primary outcome compared the pre-and post-antibiotic International Normalized Ratio (INR) of patients in the intervention group (warfarin dose reduction) with those in the control group (no intervention). Secondary outcomes assessed incidence of thromboembolic and major bleeding events within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine patients had at least one follow-up appointment; 126 follow-up visits were evaluated. There was a statistically significant difference for the change in therapeutic INR at the first follow-up appointment (p = 0.029) for those patients in the control group. On average, the patients in the intervention group required fewer follow-up visits (p = 0.019). There were no statistically significant differences for the overall rate of therapeutic INR values between groups, as well as no instances of a thromboembolic or major bleeding events during the follow-up period. Clinically significant differences were observed for patients who received a preemptive warfarin dose reduction upon initiation of sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention group required fewer follow-up appointments and were more likely maintain a therapeutic INR within the 30 days following the antibiotic course. Results of this study will be presented the at Pharmacy and Therapeutics committee in an effort to seek approval for policy development to initiate a local preemptive warfarin dose adjustment as a standard

  20. Bleeding events with dabigatran or warfarin in patients with venous thromboembolism.

    Science.gov (United States)

    Majeed, Ammar; Goldhaber, Samuel Z; Kakkar, Ajay; Kearon, Clive; Eriksson, Henry; Kreuzer, Jörg; Feuring, Martin; Hantel, Stephan; Friedman, Jeffrey; Schellong, Sebastian; Schulman, Sam

    2016-01-01

    Dabigatran was as effective as warfarin for the acute treatment of venous thromboembolism in the RE-COVER and RE-COVER II trials. We compared the incidence of bleeding with dabigatran versus warfarin in pooled data from these studies. The localisation, bleeding severity, and the impact of key factors on the incidence of bleeding, were compared between the dabigatran and warfarin treatment group. Altogether, 2553 patients received dabigatran and 2554 warfarin, each for a mean of 164 days. The incidence of any bleeding event was significantly lower with dabigatran (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.61-0.79), as was the incidence of the composite of MBEs and clinically relevant non-major bleeding events (HR 0.62; 95% CI, 0.50-0.76). The incidence of major bleeding events (MBEs) was also significantly lower with dabigatran in the double-dummy phase (HR, 0.60; 95%CI, 0.36-0.99) but not statistically different between the two treatment arms when the entire treatment period is considered (HR 0.73 95% CI, 0.48-1.11). Increasing age, reduced renal function, Asian ethnicity, and concomitant antiplatelet therapy were associated with higher bleeding rates in both treatment groups. The reduction in bleeding with dabigatran compared to warfarin was consistent among the subgroups and with a similar pattern for intracranial, and urogenital major bleeding. In conclusion, treatment of venous thromboembolism with dabigatran is associated with a lower risk of bleeding compared to warfarin. This reduction did not differ with respect to the location of bleeding or among predefined subgroups.

  1. Cost-effectiveness of apixaban compared with warfarin for stroke prevention in atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Soyon Lee

    Full Text Available BACKGROUND: Apixaban was shown to be superior to adjusted-dose warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation (AF and at least one additional risk factor for stroke, and associated with reduced rates of hemorrhage. We sought to determine the cost-effectiveness of using apixaban for stroke prevention. METHODS: Based on the results from the Apixaban Versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE trial and other published studies, we constructed a Markov model to evaluate the cost-effectiveness of apixaban versus warfarin from the Medicare perspective. The base-case analysis assumed a cohort of 65-year-old patients with a CHADS(2 score of 2.1 and no contraindication to oral anticoagulation. We utilized a 2-week cycle length and a lifetime time horizon. Outcome measures included costs in 2012 US$, quality-adjusted life-years (QALYs, life years saved and incremental cost-effectiveness ratios. RESULTS: Under base case conditions, quality adjusted life expectancy was 10.69 and 11.16 years for warfarin and apixaban, respectively. Total costs were $94,941 for warfarin and $86,007 for apixaban, demonstrating apixaban to be a dominant economic strategy. Upon one-way sensitivity analysis, these results were sensitive to variability in the drug cost of apixaban and various intracranial hemorrhage related variables. In Monte Carlo simulation, apixaban was a dominant strategy in 57% of 10,000 simulations and cost-effective in 98% at a willingness-to-pay threshold of $50,000 per QALY. CONCLUSIONS: In patients with AF and at least one additional risk factor for stroke and a baseline risk of ICH risk of about 0.8%, treatment with apixaban may be a cost-effective alternative to warfarin.

  2. Coordination properties of warfarin towards Pr(III) predicted from DFT and FT-IR studies

    Energy Technology Data Exchange (ETDEWEB)

    Mihaylov, Tz., E-mail: tzmihay@svr.igic.bas.bg [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Trendafilova, N.; Georgieva, I. [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, Sofia (Bulgaria); Kostova, I., E-mail: irenakostova@yahoo.com [Department of Chemistry, Faculty of Pharmacy, Medical University, Sofia (Bulgaria)

    2010-08-23

    Graphical abstract: The coordination behavior of warfarin towards Pr(III) in Pr(L){sub 3}.5H{sub 2}O complex (L - warfarin) is investigated through molecular modeling at B3LYP/6-31G(d,p) level and consequent exhaustive comparative vibrational analysis of the ligand and the complex. The calculations predicted that the ligand binds to the metal through the deprotonated enol group and the keto C=O group in pseudo-octahedral polyhedron. The simulated vibrational spectrum of the model complex proposed is in excellent agreement with the experimental one. - Abstract: The coordination behavior of warfarin towards Pr(III) in Pr(L){sub 3}.5H{sub 2}O complex (L - warfarin) is investigated through molecular modeling at B3LYP/6-31G(d,p) level and consequent exhaustive comparative vibrational analysis of the ligand and the complex. The calculated NPA charges, Fukui functions and MEP values of the anionic ligand in solution pointed out that the oxygen atoms of the deprotonated hydroxyl and the coumarin carbonyl groups are the most probable reactive sites upon coordination. The metal-ligand binding mode of warfarin is predicted through molecular modeling and energy estimation of different Pr(III)-warfarin structures. In the most stable model structure, the ligand-metal binding is realized through the oxygen of the deprotonated OH group and the oxygen of the keto C=O group in pseudo-octahedral polyhedron. The suggested metal-ligand binding mode is confirmed by comparative vibrational analysis of the free ligand and various model structures with different metal-ligand binding modes.

  3. Comparison of initial loading doses of 5 mg and 10 mg for warfarin therapy

    Directory of Open Access Journals (Sweden)

    Sidnei Lastória

    2014-03-01

    Full Text Available CONTEXT: The question of what is the best loading dosage of warfarin when starting anticoagulant treatment has been under discussion for ten years. We were unable to find any comparative studies of these characteristics conducted here in Brazil. OBJECTIVE: To compare the safety and efficacy of two initial warfarin dosage regimens for anticoagulant treatment. METHODS: One-hundred and ten consecutive patients of both sexes, with indications for anticoagulation because of venous or arterial thromboembolism, were analyzed prospectively. During the first 3 days of treatment, these patients were given adequate heparin to keep aPTT (activated partial thromboplastin time between 1.5 and 2.5, plus 5 mg of warfarin. From the fourth day onwards, their warfarin doses were adjusted using International Normalized Ratios (INR; target range: 2 to 3. This prospective cohort was compared with a historical series of 110 patients had been given 10 mg of warfarin on the first 2 days and 5 mg on the third day with adjustments based on INR thereafter. Outcomes analyzed were as follows: recurrence of thromboembolism, bleeding events and time taken to enter the therapeutic range. RESULTS: Efficacy, safety and length of hospital stay were similar in both samples. The sample that were given 10 mg entered the therapeutic range earlier (means: 4.5 days vs. 5.8 days, were on lower doses at discharge and had better therapeutic indicators at the first return appointment. CONCLUSIONS: The 10 mg dosage regimen took less time to attain the therapeutic range and was associated with lower warfarin doses at discharge and better INR at first out-patients follow-up visit.

  4. Computational design of an enantioselective molecular imprinted polymer for the solid phase extraction of S-warfarin from plasma.

    Science.gov (United States)

    Ahmadi, F; Yawari, E; Nikbakht, M

    2014-04-18

    An enantioselective molecular imprinted polymer for S-warfarin was designed computationally by using the density functional theory (DFT) at B3LYP/631G+ (d, p) level and Gaussian 2003 package. The effect of polymerization solvent was also evaluated by the polarizable continuum model (PCM) and it was based on the measurement of interaction energies (ΔE) between S-warfarin and monomers in different polymerization solvents. The computational method showed that the methacrylic acid (MAA) and acetonitrile (AN) had the highest stabilization energy for the pre-polymerization adducts. Additionally, the mole ratio of 1:3 give the highest ΔE, therefore, the polymer was synthesized by the thermal bulk polymerization method with the mole ratio of S-warfarin-(MAA)3. The enantioselective extraction of MIP for R and S-warfarin was evaluated by chiral separation chromatography and polarimetry methods. The results revealed that the proposed S-warfarin molecular imprinted polymer has a moderate recognition for extraction of R-warfarin in a racemic mixture and had no recognition for other foreign drugs. In a racemic mixture of R and S-warfarin, the polymer is able to remove about 20% of R-warfarin. The linearity between responses (peak areas) and concentrations of S-warfarin in plasma sample was found in the range of 15.4-3080ngmL(-1) (R(2)=0.999).The linear range for a racemic mixture of R, S-warfarin in plasma which has been obtained by RP-C18-HPLC-UV method, was 12.0-2500ngmL(-1) (R(2)=0.998). The polymer was used for analysis of a real sample and as expected the accurate results were obtained.

  5. Benefit of Warfarin Compared With Aspirin in Patients With Heart Failure in Sinus Rhythm

    Science.gov (United States)

    Homma, Shunichi; Thompson, John L.P.; Sanford, Alexandra R.; Mann, Douglas L.; Sacco, Ralph L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J.P.; Massie, Barry M.; Labovitz, Arthur J.; Di Tullio, Marco R.; Gabriel, André P.; Lip, Gregory Y.H.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

    2014-01-01

    Background The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference in the primary outcome between warfarin and aspirin in 2305 patients with reduced left ventricular ejection fraction in sinus rhythm. However, it is unknown whether any subgroups benefit from warfarin or aspirin. Methods and Results We used a Cox model stepwise selection procedure to identify subgroups that may benefit from warfarin or aspirin on the WARCEF primary outcome. A secondary analysis added major hemorrhage to the outcome. The primary efficacy outcome was time to the first to occur of ischemic stroke, intracerebral hemorrhage, or death. Only age group was a significant treatment effect modifier (P for interaction, 0.003). Younger patients benefited from warfarin over aspirin on the primary outcome (4.81 versus 6.76 events per 100 patient-years: hazard ratio, 0.63; 95% confidence interval, 0.48–0.84; P=0.001). In older patients, therapies did not differ (9.91 versus 9.01 events per 100 patient-years: hazard ratio, 1.09; 95% confidence interval, 0.88–1.35; P=0.44). With major hemorrhage added, in younger patients the event rate remained lower for warfarin than aspirin (5.41 versus 7.25 per 100 patient-years: hazard ratio, 0.68; 95% confidence interval, 0.52–0.89; P=0.005), but in older patients it became significantly higher for warfarin (11.80 versus 9.35 per 100 patient-years: hazard ratio, 1.25; 95% confidence interval, 1.02–1.53; P=0.03). Conclusions In patients <60 years, warfarin improved outcomes over aspirin with or without inclusion of major hemorrhage. In patients ≥60 years, there was no treatment difference, but the aspirin group had significantly better outcomes when major hemorrhage was included. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. PMID:23881846

  6. Indikation for behandling med warfarin bør altid fremgå eksplicit ved sektorskifte

    DEFF Research Database (Denmark)

    Vestergaard, Thea; Hjort, Johanne; Madsen, Henrik Bjørnsgaard

    2014-01-01

    Warfarin has a narrow therapeutic window and side effects include bleeding causing e.g. hospital admission and death. Monitoring of treatment and review of indication are mandatory. We report a case of more than four years of warfarin treatment without indication. Treatment was not discontinued due...... to inadequate medical record keeping and communication among health-care providers. Medical-record keeping should follow guidelines from the National Board of Health. In addition, clearly stated treatment duration and indication may prevent unwarranted or premature termination of treatment....

  7. Research progress in CYP2C9 and VKORC1 gene polymorphism and individualized warfarin therapeutic regimen

    Directory of Open Access Journals (Sweden)

    Yue-ping LIU

    2015-04-01

    Full Text Available Warfarin is still the most clinically used oral anti-coagulant despite of its narrow therapeutic index and high risk of hemorrhage. The mean daily dose of warfarin varies widely from patient to patient, and to achieve the same therapeutic effect, the daily dose of warfarin could be varied over 20-fold. The variability in warfarin dosage depends on several factors, including gene polymorphisms, index of body mass, age and other drugs, and these factors compelled the clinicians to individualize warfarin dosage in order to optimize the therapeutic regimen. A number of genes are involved in metabolism of warfarin, such as cytochrome P450 2C9 (CYP2C9, vitamin K epoxide reductase complex subunit 1 (VKORC1, cytochrome P450 4F2 (CYP4F2, gamma-glutamylcarboxylase (GGCX, etc. Of them CYP2C9 and VKORC1 are the emphasis of current researches. The association between the polymorphism of CYP2C9 and VKORC1 and individualized warfarin therapeutic regimen are mainly discussed in this paper. DOI: 10.11855/j.issn.0577-7402.2015.02.16

  8. Anticoagulation Stability Depends on CHADS2 Score and Hepatorenal Function in Warfarin-treated Patients, Including Those with Atrial Fibrillation

    Science.gov (United States)

    Odashiro, Keita; Fukata, Mitsuhiro; Arita, Takeshi; Maruyama, Toru; Akashi, Koichi

    2017-01-01

    Aim: Although warfarin remains important despite the widespread use of nonvitamin K antagonist oral anticoagulants (NOACs), to date, the reality of warfarin use in the “NOACs era” is unclear. This multicenter observational study aimed to clarify the key factors contributing to warfarin treatment stability. Methods: The practical use of warfarin, stability of warfarin therapy, and factors contributing to this stability were investigated in community-based hospitals through a real-world study. Clinical data were retrospectively extracted from the medical records of warfarin-treated Japanese patients (age, 71.3 ± 5.5 years) with atrial fibrillation (AF), prosthetic heart valve, or other concerns requiring anticoagulation. Treatment stability was considered as time in therapeutic range of international normalized ratio of prothrombin time (TTR: %). The factors contributing to TTR were investigated, including CHADS2 score components. Results: Mean CHADS2 score was highest (1.38 ± 0.88, p antiplatelet agents did not correlate with the low TTR. Conclusions: This retrospective study demonstrated that the CHADS2 score component accumulation and hepatorenal dysfunction are factors significantly contributing to the low TTR, which is indicative of poor warfarin treatment stability, in patients such as those with AF. PMID:27319745

  9. Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers.

    Science.gov (United States)

    Robertson, Philmore; Hellriegel, Edward T; Arora, Sanjay; Nelson, Michael

    2002-02-01

    Modafinil has been reported to produce a concentration-related suppression of CYP2C9 activity in vitro in primary cultures of human hepatocytes. To determine whether this effect occurs in vivo, the pharmacokinetics of (S)-warfarin was investigated after single oral doses of racemic warfarin (5 mg; COUMADIN) in a placebo-controlled, single-blind, single-period study in 28 volunteers. Subjects received an oral dose of warfarin prior to administration of modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo and they received another after 4 weeks of treatment. Treatment with modafinil did not significantly alter the pharmacokinetics of (S)- or (R)-warfarin relative to placebo. Since (S)-warfarin is predominantly metabolized via CYP2C9, the results indicate that the marked suppression of CYP2C9 activity in vitro does not translate into a similar effect clinically. However, limitations arising from investigation of single doses of warfarin preclude global conclusions about the potential for more subtle interactions after chronic warfarin administration.

  10. [Pharmaceutical care of serious bleeding induced by tramadol-warfarin interaction: a case report].

    Science.gov (United States)

    Dong, Shu-jie; Zhang, Ting; Li, Yan; Zhai, Suo-di

    2014-10-18

    Warfarin is a high-alert medication, which may result in bleeding if used improperly. In our case, one elderly female with atrial fibrillation had taken warfarin for more than half a year, and her international normalized ratio (INR) was maintained within the therapeutic range. The patient began to take tramadol to alleviate her shoulder pain. Three days later she presented hematuresis and had ecchymosis in her right upper arm, and in the meantime her INR rose to 10.04. Clinical pharmacists analyzed the cause for bleeding by searching relevant literature, and finally discovered the interaction between warfarin and tramadol. On the basis of that, the clinical pharmacists provided pharmaceutical care, offered specific medication education, as well as assisted the physicians to establish the medication plan for warfarin reuse. Eventually, her INR declined to reference ranges, and her hematuresis and ecchymosis were alleviated significantly. This successful case reveals that clinical pharmacy services contribute to better treatment outcomes. Clinical pharmacists can play an active role in anticoagulation management in healthcare team.

  11. Pharmacogenetic-guided dosing of coumarin anticoagulants : Algorithms for warfarin, acenocoumarol and phenprocoumon

    NARCIS (Netherlands)

    Verhoef, Talitha I.; Redekop, William K.; Daly, Ann K.; Van Schie, Rianne M F; De Boer, Anthonius; Maitland-Van Der Zee, Anke Hilse

    2014-01-01

    Coumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with couma

  12. Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events

    DEFF Research Database (Denmark)

    Rost, Natalia S; Giugliano, Robert P; Ruff, Christian T

    2016-01-01

    BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients with ver...... IS or TIA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391....

  13. Development of predictive models for estimating warfarin maintenance dose based on genetic and clinical factors.

    Science.gov (United States)

    Yang, Lu; Linder, Mark W

    2013-01-01

    In this chapter, we use calculation of estimated warfarin maintenance dosage as an example to illustrate how to develop a multiple linear regression model to quantify the relationship between several independent variables (e.g., patients' genotype information) and a dependent variable (e.g., measureable clinical outcome).

  14. Using a personalized decision support algorithm for dosing in warfarin treatment: A randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Peter Brønnum Nielsen

    2017-01-01

    Conclusions: We found no difference between the two trial-arms in a high-quality warfarin treatment setup. However in general, the model performed similarly as to routine patient self-management care. (ClinicalTrials.gov number: NCT02705976

  15. Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation

    DEFF Research Database (Denmark)

    Lau, Wallis C Y; Chan, Esther W; Cheung, Ching-Lung

    2017-01-01

    .7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk...

  16. Balancing individual benefits and risks of warfarin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Van Den Ham, Rianne; Klungel, Olaf H.; Leufkens, Hubert G.M.; Van Staa, Tjeerd P.

    2013-01-01

    Background: Anticoagulation with warfarin reduces the risk of ischaemic stroke in patients with atrial fibrillation (AF) but may increase the risk of bleeding. A positive benefit-risk balance in the overall AF population has been well established, but hardly studied on an individual level.

  17. A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics.

    Directory of Open Access Journals (Sweden)

    Jorge Duconge

    Full Text Available This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients.A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals.The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day, and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001. The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias.Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics.ClinicalTrials.gov NCT01318057.

  18. The Cost Differential Between Warfarin Versus Aspirin Treatment After a Fontan Procedure.

    Science.gov (United States)

    Schilling, Chris; Dalziel, Kim; Iyengar, Ajay J; d'Udekem, Yves

    2017-08-01

    The use of aspirin versus warfarin for treatment of patients after a Fontan procedure remains contentious. Current preference-based models of treatment across Australia and New Zealand show variation in care that is unlikely to reflect patient differences and/or clinical risk. We combine data from the Australian and New Zealand Fontan Registry and a home INR (International Normalised Ratio) monitoring program (HINRMP) from the Royal Children's Hospital (RCH) Melbourne, to estimate the cost difference for Fontan recipients receiving aspirin versus warfarin for 2015. We adopt a societal perspective to costing which includes cost to the health system (e.g. medical consults, pathology tests) and costs to patients and carers (e.g. travel and time), but excludes costs of adverse events. Costs are presented in Australian 2015 dollars; any costs from previous years have been inflated using appropriate rates from the Australian Bureau of Statistics. We find that warfarin patients face additional costs of $825 per annum, with the majority ($584 or 71%) of those borne by the patient or family. If aspirin is as clinically as effective as warfarin, Fontan recipients could be enjoying far less costly, invasive and time-consuming treatment. While achieving such clinical consensus can be difficult, economics shows us that there are large costs associated with a failure to achieve it. Copyright © 2017. Published by Elsevier B.V.

  19. Is warfarin usage a risk factor for osteoporotic fractures? A cohort study in the emergency department

    Directory of Open Access Journals (Sweden)

    Genady Drozdinsky

    2017-04-01

    Full Text Available Background Several studies have examined the association between warfarin sodium use and risk of osteoporotic fractures with conflicting results. Our study addresses this question, for the first time regarding patients attending emergency department (ED. Aims The aim of this study was to retrospectively detect whether there is higher rate of usage of warfarin sodium in patients with osteoporotic fractures attending an ED. Methods This is a retrospective study from patients' computerized charts. All individuals >65 years old who had an osteoporotic fracture and attended an ED in a tertiary hospital were compared with a similar group of elderly individuals >65 years old without an osteoporotic fracture who attended the ED for a cause other than an osteoporotic fracture. Results This study included 328 patients who were evaluated in the years 2005–2016. Overall, 164 individuals with a typical osteoporotic fracture (hip -66 patients (40 per cent, spine- 92 patients (56 per cent, humerus -4 patients (2 per cent, radius -13 patients (8 per cent were identified and compared with a matched group of elderly individuals who were evaluated in the ED for other complaints. Warfarin sodium was used in 61 individuals (19 per cent in the entire cohort, 34 in the fracture group and 27 in the non-fracture group (p=0.324. Conclusion In elderly patients, attending an ED, warfarin sodium use does not seem to be a risk factor for an osteoporotic fracture

  20. Warfarin therapy in a dog with acute arterial thrombosis and pyometra.

    Science.gov (United States)

    Arai, Shiori; Callan, Mary Beth

    2014-11-01

    This report describes the presentation of acute arterial thrombosis causing triparesis in a 6-year-old female Chihuahua with pyometra and its successful management in combination with warfarin therapy. This is the first case report of a dog with arterial thrombosis associated with pyometra.

  1. Fatal cerebral blødning på grund af mulig interaktionmellem paracetamol og warfarin

    DEFF Research Database (Denmark)

    Vinsand Naver, Signe; Papina, Maria; Jimenez Solem, Espen

    2015-01-01

    This is a case report of an 83-year-old man in warfarin treatment with stable international normalised ratio (INR) after aortic valve replacement and atrial fibrillation. Due to back pain he took paracetamol (acetaminophen) 4 g/day, morphine 30 mg/day and diclofenac as rescue medication for two...

  2. Lipase-supported metal-organic framework bioreactor catalyzes warfarin synthesis.

    Science.gov (United States)

    Liu, Wan-Ling; Yang, Ni-Shin; Chen, Ya-Ting; Lirio, Stephen; Wu, Cheng-You; Lin, Chia-Her; Huang, Hsi-Ya

    2015-01-02

    A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase-supported metal-organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. New cerebral microbleeds in ischemic stroke patients on warfarin treatment: two-year follow-up.

    Science.gov (United States)

    Orken, D Necioglu; Uysal, E; Timer, E; Kuloglu-Pazarcı, N; Mumcu, S; Forta, H

    2013-09-01

    Cerebral microbleeds (CMBs) are known to be indicative of bleeding-prone microangiopathy. Little is known about the significance of CMBs in anticoagulated patients. We determined the frequency of new CMBs in ischemic stroke patients who had been receiving warfarin treatment for 2 years. A total of 204 ischemic stroke patients on warfarin therapy for 2 years underwent a repeat MRI. We compared demographic features, vascular risk factors, and radiological findings of patients with and without new CMBs. New CMBs on gradient-echo MRI were found in 29 of 204 patients (10%). Of 35 patients who had CMBs in the original study, 9 developed new CMBs after 2 years (26%), compared with 20 of the 169 patients (12%) who did not have CMBs at baseline (p=0.03). Patients with new CMBs were older than patients without CMBs (p=0.04), and the frequency of leukoaraiosis was significantly higher (p=0.02). The mean duration of warfarin treatment was not significantly different between the patients with and without new CMBs (p=0.28). This longitudinal study suggested that the presence of CMBs at baseline increased the frequency of new CMBs in patients on warfarin therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack

    DEFF Research Database (Denmark)

    Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia

    2012-01-01

    In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy ...

  5. Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient

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    Dagmar F. Hernandez-Suarez MD

    2016-12-01

    Full Text Available Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1*2 (g.559C>T, p.P187S polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

  6. Cloud point extraction-fluorimetric combined methodology for the determination of trace warfarin based on the sensitization effect of supramolecule

    Energy Technology Data Exchange (ETDEWEB)

    Chang Zheng [Department of Applied Chemistry of College of Science, Xi' an University of Technology, Xi' an 710048 (China); College of Chemistry and Materials Science, Northwest University, 229 North Taibai Road, Xi' an 710069 (China); Yan Hongtao, E-mail: cz610@163.com [College of Chemistry and Materials Science, Northwest University, 229 North Taibai Road, Xi' an 710069 (China)

    2012-03-15

    Compared to the fluorescence spectra of warfarin in pure ethanol and in the presence of the nonionic surfactant Tergitol 15-S-7 after cloud point extraction (CPE), it can be seen that the fluorescence emission peak underwent an obvious red shift and the fluorescence intensity of warfarin was significantly increased in the presence of Tergitol 15-S-7. In order to confirm Tergitol 15-S-7-induced supramolecular effects, the investigations on the fluorescence quantum yields of warfarin in the micellar medium and pure ethanol were performed. The experimental results showed that the supramolecular interactions between Tergitol 15-S-7 and the warfarin excimers played a key role for improving the warfarin fluorescence properties. Based on these facts, a simple fluorometric method combined with CPE for the determination of trace warfarin was developed for the first time. Under optimized experimental conditions, the linear concentration range for warfarin was 3.0 Multiplication-Sign 1.0{sup -9}-1.0 Multiplication-Sign 10{sup -6} mol L{sup -1} and the detection limit was 3.3 Multiplication-Sign 10{sup -10} mol L{sup -1}. And, the proposed method was approved to be appropriate for monitoring warfarin in actual pharmaceutical formulations and biological fluid samples by recovery test, in comparison with other reported methods being satisfactory. - Highlights: Black-Right-Pointing-Pointer A CPE fluorescence method for trace warfarin was developed for the first time. Black-Right-Pointing-Pointer Supramolecule effects play a key role for improving the fluorescence property. Black-Right-Pointing-Pointer Notion presents an opportunity so far neglected area of CPE investigation. Black-Right-Pointing-Pointer Without previous treatment, urine species after CPE had no significant interference.

  7. Differential Effects of Dabigatran and Warfarin on Bone Volume and Structure in Rats with Normal Renal Function

    Science.gov (United States)

    Fusaro, Maria; Dalle Carbonare, Luca; Dusso, Adriana; Arcidiacono, Maria Vittoria; Valenti, Maria Teresa; Aghi, Andrea; Pasho, Sabina; Gallieni, Maurizio

    2015-01-01

    Background Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin) and Matrix Gla Protein (MGP). Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification. Methods Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically. Results Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries. Conclusions These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients. PMID:26241483

  8. Differential Effects of Dabigatran and Warfarin on Bone Volume and Structure in Rats with Normal Renal Function.

    Directory of Open Access Journals (Sweden)

    Maria Fusaro

    Full Text Available Warfarin, a widely used anticoagulant, is a vitamin K antagonist impairing the activity of vitamin K-dependent Bone Gla Protein (BGP or Osteocalcin and Matrix Gla Protein (MGP. Because dabigatran, a new anticoagulant, has no effect on vitamin K metabolism, the aim of this study was to compare the impact of warfarin and dabigatran administration on bone structure and vascular calcification.Rats with normal renal function received for 6 weeks warfarin, dabigatran or placebo. Bone was evaluated immuno-histochemically and hystomorphometrically after double labelling with declomycin and calcein. Aorta and iliac arteries were examined histologically.Histomorphometric analysis of femur and vertebrae showed significantly decreased bone volume and increased trabecular separation in rats treated with warfarin. Vertebra analysis showed that the trabecular number was higher in dabigatran treated rats. Osteoblast activity and resorption parameters were similar among groups, except for maximum erosion depth, which was higher in warfarin treated rats, suggesting a higher osteoclastic activity. Therefore, warfarin treatment was also associated with higher bone formation rate/bone surface and activation frequency. Warfarin treatment may cause an increased bone turnover characterized by increased remodelling cycles, with stronger osteoclast activity compared to the other groups. There were no differences among experimental groups in calcium deposition either in aortic or iliac arteries.These findings suggest for the first time that dabigatran has a better bone safety profile than warfarin, as warfarin treatment affects bone by reducing trabecular size and structure, increasing turnover and reducing mineralization. These differences could potentially result in a lower incidence of fractures in dabigatran treated patients.

  9. Biopsy of the prostate guided by transrectal ultrasound: relation between warfarin use and incidence of bleeding complications

    Energy Technology Data Exchange (ETDEWEB)

    Ihezue, C.U. [Department of Radiology, Southampton General Hospital (United Kingdom); Smart, J. [Department of Radiology, Southampton General Hospital (United Kingdom); Dewbury, K.C. [Department of Radiology, Southampton General Hospital (United Kingdom)]. E-mail: keith.dewbury@suht.swest.nhs.uk; Mehta, R. [Department of Radiology, Southampton General Hospital (United Kingdom); Burgess, L. [Department of Radiology, Southampton General Hospital (United Kingdom)

    2005-04-01

    AIM: To determine the relation between warfarin use and the frequency of bleeding complications after biopsy of the prostate guided by transrectal ultrasound (TRUS). METHODS: Overall, 1022 consecutive patients with suspected prostatic disease were followed after biopsy. Warfarin and aspirin use was determined on the day of the procedure. A TRUS-guided biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications. Follow-up telephone calls were made to those who had not replied within the stipulated period. RESULTS: Of the 1000 patients who replied, 49 were receiving warfarin, 220 were receiving aspirin and 731 were not receiving any anticoagulant drugs. Of the 49 subjects reporting current use of warfarin, 18 (36.7%) experienced haematuria, compared with 440 (60.2%) of the patients receiving no anti-coagulant drugs who reported haematuria. This was statistically significant (p=0.001). Of the group receiving warfarin, 4 (8.2%) experienced haematospermia whereas 153 (21%) of the group receiving no anticoagulant medication reported haematospermia. This difference also was statistically significant (p=0.030). Rectal bleeding was experienced by 7 (14.3%) of the group receiving warfarin compared with 95 (13%) in the group without anticoagulant medication, but this was not statistically significant (p=0.80). We also demonstrated that there was no statistically significant association between the severity of the bleeding complications and medication with warfarin. CONCLUSION: None of the group receiving warfarin experienced clinically important bleeding complications. Our results suggest that the frequency and severity of bleeding complications were no worse in the warfarin group than in the control group and that discontinuing anticoagulation medication before prostate biopsy may be unnecessary.

  10. Warfarin-induced skin necrosis in HIV-1-infected patients with tuberculosis and venous thrombosis.

    Science.gov (United States)

    Bhaijee, F; Wainwright, H; Meintjes, G; Wilkinson, R J; Todd, G; De Vries, E; Pepper, D J

    2010-06-01

    At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB). We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/microl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 6.2 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The

  11. Dental extraction in patients on warfarin treatment: a series of 35 patients

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    Abdullah WA

    2014-08-01

    Full Text Available Walid Ahmed Abdullah,1,2 Hesham Khalil1 1Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Oral and Maxillofacial Surgery, College of Dentistry, Mansoura University, Mansoura, Egypt Background: Warfarin is one of the most common oral anticoagulants used to prevent thromboembolic episodes. The benefits of discontinuation of this drug before simple surgical procedures are not clear and this approach could be associated with complications. The aim of this study was to evaluate the risk of bleeding in a series of 35 patients (in cases where the international normalized ratio [INR] is less than 4 following simple tooth extraction without modification of the warfarin dose given to patients. Methods: Thirty-five patients taking warfarin who had been referred to the Oral and Maxillofacial Department, College of Dentistry, King Saud University, for dental extractions were included in the study. Exclusion criteria included patients with an INR of ≥4 or with a history of liver disease or coagulopathies. No alteration was made in warfarin dose, and the CoaguChek System was used to identify the INR on the same day of dental extraction. Bleeding from the extraction site was evaluated and recorded immediately after extraction until the second day. Results: A total of 35 patients (16 women and 19 men aged between 38 and 57 years (mean =48.7 were included in the present study. All patients underwent simple one-tooth extraction while undergoing warfarin treatment. Oozing, considered mild bleeding and which did not need intervention was seen in 88.6% of patients. Moderate bleeding occurred in 11.4% of all cases. The INR of the patients ranged from 2.00 to 3.50, with 77.2% of patients having INR between 2.0 and 2.5 on the day of extraction. No severe bleeding which needed hospital management was encountered after any of the extractions. The patients who suffered moderate

  12. Reinitiating Warfarin: Relationships Between Dose and Selected Patient, Clinical and Hospital Measures

    Science.gov (United States)

    Leonhard, Lucas G.; Berg, Richard L.; Burmester, James K.; Mazza, Joseph J.; Schmelzer, John R.; Yale, Steven H.

    2015-01-01

    Background Warfarin is an oral anticoagulant used in the long-term treatment/prevention of venothromboembolic disease. Patients undergoing elective surgical and non-surgical procedures may require temporary warfarin discontinuation followed by reinitiation after their procedure. Because little information is available regarding best methods for warfarin reinitiation, we investigated current practices to inform management decisions. Methods Subjects were required to have a known and stable warfarin dose prior to discontinuation, which was operationalized by requiring, within 7-days prior to discontinuation, that they have at least one INR in therapeutic range (2.0–3.5), no INR(s) out of range, and no more than a 15% change in warfarin dose. Stable dose prior to discontinuation was defined as the average daily dose received in the 7 days immediately prior to discontinuation. Reinitiation dose was defined as the average daily dose received in the first 3 days after warfarin was restarted. Subjects were divided into three groups based on whether they received approximately the same, a higher, or a lower dose at reinitiation and were also grouped by calendar time into three distinct periods that reflected differing levels of availability of electronic and patient care data that may impact reinitiation dose decisions. These groupings facilitated analyses and descriptions of trends in reinitiation dosing and supported other analyses, including tests for association between dose group and selected subject demographic, clinical, medication and hospitalization measures. All study data were abstracted from Marshfield Clinic electronic patient care and administrative databases and electronic patient care databases from Ministry St. Joseph’s Hospital (Marshfield, WI). Results We identified 205 subjects with warfarin temporarily discontinued between 1994 and 2012: 99 subjects in same dose group, 32 subjects in the low group, and 74 subjects in the high group. Because

  13. Trans-Resveratrol Enhances the Anticoagulant Activity of Warfarin in a Mouse Model

    Science.gov (United States)

    Kimura, Yuka; Suzuki, Sachina; Tatefuji, Tomoki; Umegaki, Keizo

    2016-01-01

    Aim: Resveratrol is a popular ingredient in dietary supplements. Some patients concomitantly use dietary supplements and medicines in Japan. In the present study, we determined whether trans-resveratrol and melinjo (Gnetum gnemon L.) seed extract (MSE), which contains resveratrol dimers, interacted with drugs using a mouse model. Methods: Male C57BL/6J mice were fed experimental diets containing 0.005%, 0.05%, or 0.5% (w/w) trans-resveratrol or MSE for 1 or 12 weeks. The expression of liver cytochrome P-450 (CYP) mRNA and activity of liver microsomal CYP were measured. To determine the influence of resveratrol or MSE on drug efficacy, the anticoagulant activity of warfarin was examined in mice that were fed diets containing trans-resveratrol or MSE for 12 weeks. Results: When the mice were fed experimental diets for 1 week, none of the doses of trans-resveratrol and MSE affected body weight, liver weight, or plasma AST and ALT levels. Trans-resveratrol also did not affect CYP1A1, CYP1A2, CYP2C, or CYP3A activities. In contrast, 0.5% MSE slightly increased CYP1A1 activity. When the mice were fed experimental diets for 12 weeks, 0.05% trans-resveratrol increased CYP1A1, CYP2C, and CYP3A activities, whereas 0.5% MSE suppressed CYP3A activity. Under these conditions, 0.5% trans-resveratrol enhanced the anticoagulant activity of warfarin, although CYP2C activity increased. However, MSE did not affect the anticoagulant activity of warfarin. Conclusion: The 0.05% trans-resveratrol did not interact with warfarin in a mouse model, whereas 0.5% trans-resveratrol may have enhanced the anticoagulant activity of warfarin. PMID:26947597

  14. Assessing the quality, suitability and readability of internet-based health information about warfarin for patients

    Directory of Open Access Journals (Sweden)

    Sayeed Nasser

    2012-03-01

    Full Text Available BackgroundWarfarin is a high-risk medication where patient information may be critical to help ensure safe and effective treatment. Considering the time constraints of healthcare providers, the internet can be an important supplementary information resource for patients prescribed warfarin. The usefulness of internet-based patient information is often limited by challenges associated with finding valid and reliable health information. Given patients’ increasing access of the internet for information, this study investigated the quality, suitability and readability of patient information about warfarin presented on the internet.MethodPreviously validated tools were used to evaluate the quality, suitability and readability of patient information about warfarin on selected websites.ResultsThe initial search yielded 200 websites, of which 11 fit selection criteria, comprising seven non-commercial and four commercial websites. Regarding quality, most of the non-commercial sites (six out of seven scored at least an ‘adequate’ score. With regard to suitability, 6 of the 11 websites (including two of the four commercial sites attained an ‘adequate’ score. It was determined that information on 7 of the 11 sites (including two commercial sites was written at reading grade levels beyond that considered representative of the adult patient population with poor literacy skills (e.g. school grade 8 or less.ConclusionDespite the overall ‘adequate’ quality and suitability of the internet derived patient information about warfarin, the actual usability of such websites may be limited due to their poor readability grades, particularly in patients with low literacy skills.

  15. Resource consumption and management associated with monitoring of warfarin treatment in primary health care in Sweden

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    Nilsson Gunnar H

    2006-11-01

    Full Text Available Abstract Background Warfarin is used for the prevention and treatment of various thromboembolic complications. It is an efficacious anticoagulant, but it has a narrow therapeutic range, and regular monitoring is required to ensure therapeutic efficacy and at the same time avoid life-threatening adverse events. The objective was to assess management and resource consumption associated with patient monitoring episodes during warfarin treatment in primary health care in Sweden. Methods Delphi technique was used to systematically explore attitudes, demands and priorities, and to collect informed judgements related to monitoring of warfarin treatment. Two separate Delphi-panels were performed in three and two rounds, respectively, one concerning tests taken in primary health care centres, involving 34 GPs and 10 registered nurses, and one concerning tests taken in patients' homes, involving 49 district nurses. Results In the primary health care panel 10 of the 34 GPs regularly collaborated with a registered nurse. Average time for one monitoring episode was estimated to 10.1 minutes for a GP and 21.4 minutes for a nurse, when a nurse assisted a doctor. The average time for monitoring was 17.6 minutes for a GP when not assisted by a nurse. Considering all the monitoring episodes, 11.6% of patient blood samples were taken in the individual patient's home. Average time for such a monitoring episode was estimated to 88.2 minutes. Of all the visits, 8.2% were performed in vain and took on average 44.6 minutes. In both studies, approximately 20 different elements of work concerning management of patients during warfarin treatment were identified. Conclusion Monitoring of patients during treatment with warfarin in primary health care in Sweden involves many elements of work, and demands large resources, especially when tests are taken in the patient's home.

  16. Effective feature selection of clinical and genetic to predict warfarin dose using artificial neural network

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    Mohammad Karim Sohrabi

    2016-03-01

    Full Text Available Background: Warfarin is one of the most common oral anticoagulant, which role is to prevent the clots. The dose of this medicine is very important because changes can be dangerous for patients. Diagnosis is difficult for physicians because increase and decrease in use of warfarin is so dangerous for patients. Identifying the clinical and genetic features involved in determining dose could be useful to predict using data mining techniques. The aim of this paper is to provide a convenient way to select the clinical and genetic features to determine the dose of warfarin using artificial neural networks (ANN and evaluate it in order to predict the dose patients. Methods: This experimental study, was investigate from April to May 2014 on 552 patients in Tehran Heart Center Hospital (THC candidates for warfarin anticoagulant therapy within the international normalized ratio (INR therapeutic target. Factors affecting the dose include clinical characteristics and genetic extracted, and different methods of feature selection based on genetic algorithm and particle swarm optimization (PSO and evaluation function neural networks in MATLAB (MathWorks, MA, USA, were performed. Results: Between algorithms used, particle swarm optimization algorithm accuracy was more appropriate, for the mean square error (MSE, root mean square error (RMSE and mean absolute error (MAE were 0.0262, 0.1621 and 0.1164, respectively. Conclusion: In this article, the most important characteristics were identified using methods of feature selection and the stable dose had been predicted based on artificial neural networks. The output is acceptable and with less features, it is possible to achieve the prediction warfarin dose accurately. Since the prescribed dose for the patients is important, the output of the obtained model can be used as a decision support system.

  17. Comparison of the therapeutic dose of warfarin in HIV-infected and HIV-uninfected patients: a study of clinical practice

    Science.gov (United States)

    Jackson, B S; Mokoena, T

    2017-01-01

    Background People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. Methods A prospective and retrospective descriptive study of induction time to therapeutic warfarin dose, as well as of ambulant therapeutic warfarin dose, was performed. HIV-infected and HIV-uninfected patients being treated after deep venous thrombosis with or without pulmonary embolism were compared. Sex and use of antiretroviral drugs (ARVs) were also compared in the groups. Results 234 patients were entered into the study. Induction time to therapeutic warfarin dose did not differ between the 2 groups. The mean therapeutic dose of warfarin was higher in the HIV-infected than the HIV-uninfected group: 6.06 vs 5.72 mg/day, but this was not statistically significant (p=0.29). There was no difference in therapeutic warfarin dose between ARV-naïve groups—HIV-uninfected and HIV-infected patients not on ARVs. Conclusions There appears to be little effect of HIV infection on warfarin dosing. Warfarin therapy should be administered conventionally in HIV-infected patients. PMID:28179414

  18. Medication Error When Switching from Warfarin to Rivaroxaban Leading to Spontaneous Large Ecchymosis of the Abdominal and Chest Wall

    Science.gov (United States)

    Egger, Flavio; Targa, Federica; Unterholzner, Ivan; Grant, Russell P.; Herrmann, Markus; Wiedermann, Christian J.

    2016-01-01

    Non-vitamin K oral anticoagulant (NOAC) therapy may be inappropriate if prescription was incorrect, the patient’s physiological parameters change, or interacting concomitant medications are erroneously added. The aim of this report was to illustrate inappropriate NOAC prescription in a 78-year-old woman with non-valvular atrial fibrillation and borderline renal dysfunction who was switched from warfarin to rivaroxaban and subsequently developed bruising with hemorrhagic shock and acute on chronic renal failure. Administration of 4-factor prothrombin complex concentrate effectively reversed coagulopathy and stopped bleeding. Retrospective determination of circulating plasma levels of rivaroxaban and warfarin confirmed that excessive anticoagulation was likely due to warfarin that the patient probably continued to take although rivaroxaban was initiated. Pharmacodynamic interaction between rivaroxaban and warfarin may not only be additive but synergistic. In patients at high risk of complications, judicious prescribing and dosing of NOACs, and regular monitoring of concomitant medications and renal function are highly recommended. PMID:27777713

  19. Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism.

    Science.gov (United States)

    Bazan, N S; Sabry, N A; Rizk, A; Mokhtar, S; Badary, O A

    2014-06-01

    Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and inter-ethnic variability in the warfarin dose. This study aims to assess the impact of VKORC1-1639G>A polymorphism and the most common CYP2C9 variant alleles (*2 and *3) on warfarin response in Egyptian patients. Genetic analysis of VKORC1-1639G>A and CYP2C9*2, CYP2C9*3 was performed using real-time PCR system. Patients maintained on a constant dose targeting an international normalized ratio range of 2-3.5 for at least three consecutive times were considered as good candidates. A stepwise linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on daily warfarin dose requirements. Patients carrying VKORC1 and CYP2C9 variant genotypes needed a 44.8 % lower mean daily warfarin dose as compared to wild types. Patients with G allele for VKORC1-1639G>A had a significantly higher number of thromboembolic complications per month during therapy. On the first 30 days of therapy, presence of a variant allele either in VKORC1 or in CYP2C9 was associated with increased time required to achieve stable dosing. Multiple regression analysis showed that, VKORC1-1639G>A, age, CYP2C9*3, and smoking status explained 43.4 % of the overall variability in the warfarin dose. VKORC1-1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients.

  20. Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Seljeflot Ingebjørg

    2008-06-01

    Full Text Available Abstract Background Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA alone. Aims The primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR. Methods Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC before PCR amplification (LightCycler and melting point analysis. Results The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation. Conclusion CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.

  1. Effect of Long Term Oral Warfarin Sodium Treatment on Bone Mineral Density Scores and Spinal Sagittal Alignment

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    Kamil Eyvazov

    2016-04-01

    Full Text Available Objective: The aim of this study was to investigate the effect of long term oral warfarin sodium treatment on bone mineral density (BMD and spinal sagittal alignment. Materials and Methods: Sixty four participants were enrolled for this retrospective study. Participants were divided into two groups-participants who had taken warfarin sodium for at least two years (n=33 and participants who had never taken warfarin sodium (n=31. All of the individuals were evaluated at the same center. Dual X-ray absorptiometry (DXA was used for measuring BMD. Whole spine x-rays were obtained for sagittal assessment and the following parameters were measured: Cervical lordosis, thoracic kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, sacral slope and sagittal vertical axis (SVA. Results: The mean BMD value was significantly higher in participants who had not taken warfarin sodium compared to participants who had taken warfarin sodium. The differences between the average values were 0.1552 g/cm2 in BMD; 2.1 in T scores; 1.4 in Z scores. On the radiological evaluation of the spine, cervical lordosis was 7.1 degrees lower, lumbar lordosis was 4.7 degrees lower and thoracic kyphosis was 5.3 degrees higher in the patients using drug. C7 plumb line was interchanged forward in the patients using drug. Conclusions: This study shows that warfarin sodium use worsens bone quality in the lumbar region and does not affect bone quality in the femoral region. Furthermore, warfarin sodium use also reduces physiological lordosis and enhances thoracic kyphosis. Consequences of these changes are the likely cause of sagittal spinal anterior imbalance. Long-term oral warfarin sodium use affect bone mineral density and spinal alignment. Our conclusion about giving clear message and show exactly mechanism we need prospective randomized multicentre studies in future. We strongly believe this study will be pioneer for future researches.

  2. VKORC1 and CYP2C9 genotypes are predictors of warfarin-related outcomes in children.

    Science.gov (United States)

    Shaw, Kaitlyn; Amstutz, Ursula; Hildebrand, Claudette; Rassekh, S Rod; Hosking, Martin; Neville, Kathleen; Leeder, J Steven; Hayden, Michael R; Ross, Colin J; Carleton, Bruce C

    2014-06-01

    Despite substantial evidence supporting a pharmacogenetic approach to warfarin therapy in adults, evidence on the importance of genetics in warfarin therapy in children is limited, particularly for clinical outcomes. We assessed the contribution of CYP2C9/VKORC1/CYP4F2 genotypes and variation in other genes involved in vitamin K and coagulation pathways to warfarin dose and related clinical outcomes in children. Clinical and genetic data for 93 children (age ≤ 18 years) who received warfarin therapy were obtained. DNA was genotyped for 93 selected single nucleotide polymorphisms using a custom assay. With a median age of 4.8 years, our cohort included more young children than most previous studies. Overall, 76.3% of dose variability was explained by weight, indication, VKORC1-1639G/A and CYP2C9 *2/*3, with genotypes accounting for 21.1% of variability. There was a strong correlation (R(2) = 0.68; P 4; P = 0.024) during the initiation of therapy. CYP2C9*3 carriers were also at increased risk of major bleeding while receiving warfarin (adjusted OR = 11.28). An additional variant in CYP2C9 (rs7089580) was significantly associated with warfarin dose (P = 0.020) in a multivariate clinical and genetic model. This study confirms the importance of VKORC1/CYP2C9 genotypes for warfarin dosing in a young pediatric cohort and demonstrates an impact of genetic factors on clinical outcomes in children. Furthermore, we identified an additional variant in CYP2C9 of potential relevance for warfarin dosing in children. © 2014 Wiley Periodicals, Inc.

  3. Incidence and Determinants of Traumatic Intracranial Bleeding Among Older Veterans Receiving Warfarin for Atrial Fibrillation

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    Dodson, John A.; Petrone, Andrew; Gagnon, David R.; Tinetti, Mary E.; Krumholz, Harlan M.; Gaziano, J. Michael

    2017-01-01

    Importance Traumatic intracranial bleeding, which is most commonly attributable to falls, is a common concern among clinicians who are hesitant to prescribe oral anticoagulants to older adults with atrial fibrillation. Objective To describe the incidence and risk factors for traumatic intracranial bleeding in a large cohort of older adults who are newly prescribed warfarin. Design Retrospective cohort study. Setting Department of Veterans Affairs (VA). Participants 31,951 Veterans with atrial fibrillation aged ≥75 years who were new referrals to VA anticoagulation clinics (warfarin therapy) between 1/1/2001–12/31/2012. Patients with comorbid conditions requiring warfarin were excluded. Main Outcomes and Measures The primary outcome was traumatic intracranial bleeding. Secondary outcomes included any intracranial bleeding and stroke. We used ICD-9-CM codes to identify incidence rates of these outcomes following warfarin initiation, using VA administrative data (in-system hospitalizations) and Medicare fee-for-service claims data (out-of-system hospitalizations). Clinical characteristics, laboratory, and pharmacy data were extracted from the VA electronic medical record. For traumatic intracranial bleeding, Cox proportional hazards regression was used to determine predictors of interest selected a priori based on prior known associations. Results Mean patient age was 81.1 ± 4.1 years, and comorbidities were common (hypertension 82.5%, coronary artery disease 42.6%, diabetes 33.8%). Over the study period, the incidence rate of traumatic intracranial bleeding was 4.8 per 1000 person-years. In unadjusted models, significant predictors for traumatic intracranial bleeding included dementia, fall within past year, anemia, depression, abnormal renal/liver function, anticonvulsant use, labile INR, and antihypertensive medication. After adjusting for potential confounders, the remaining significant predictors were dementia (HR 1.76, 95% CI 1.26–2.46), anemia (HR 1

  4. Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study

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    Karla Claudio-Campos

    2017-06-01

    Full Text Available Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day than common variants CYP2C9*2 and CYP2C9*3. Although, CYP2C9*2 and CYP2C9*3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs2860905 in a regression model (R2 = 0.63, MSE = 0.37 that also includes additional genetics (i.e., VKORC1-1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745 and non-genetic factors (i.e., hypertension, diabetes and age showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001. The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%. The genomic diversity of Puerto Ricans is highlighted by the presence of

  5. Hepatic cytochrome P450 mediates interaction between warfarin and Coleus forskohlii extract in vivo and in vitro.

    Science.gov (United States)

    Yokotani, Kaori; Chiba, Tsuyoshi; Sato, Yoko; Taki, Yuko; Yamada, Shizuo; Shinozuka, Kazumasa; Murata, Masatsune; Umegaki, Keizo

    2012-12-01

    This study aimed to determine whether Coleus forskohlii extract (CFE) influences the anticoagulant action of warfarin in mice in vivo and its relationship with hepatic cytochrome P450 (CYP). Mice were fed various doses of CFE standardised with 10% forskolin in a normal diet for one week, or in protein diets containing 7% and 20% casein (low and normal) for four weeks. They were then administered with warfarin by gavage on the last two days of the treatment regimen, and blood coagulation parameters, as well as hepatic CYP, were analysed at 18 h after the last dose. Direct interaction between CFE and forskolin with CYP2C was evaluated in vitro. CFE dose dependently increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a dietary level of ≥0.05%. Warfarin-induced anticoagulation was attenuated by CFE in parallel with CYP induction. The findings were similar in mice fed diets containing CFE and different ratios of protein. CFE directly inhibited CYP2C activity in mouse and human liver microsomes in vitro, whereas forskolin was only slightly inhibitory. CFE attenuates the anticoagulant action of warfarin by inducing hepatic CYP2C; thus, caution is required with the combination of warfarin and dietary supplements containing CFE. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  6. Warfarin and acetaminophen interaction: a summary of the evidence and biologic plausibility.

    Science.gov (United States)

    Lopes, Renato D; Horowitz, John D; Garcia, David A; Crowther, Mark A; Hylek, Elaine M

    2011-12-08

    Ms TS is a 66-year-old woman who receives warfarin for prevention of systemic embolization in the setting of hypertension, diabetes, and atrial fibrillation. She had a transient ischemic attack about 4 years ago when she was receiving aspirin. Her INR control was excellent; however, over the past few months it has become erratic, and her average dose required to maintain an INR of 2.0 to 3.0 appears to have decreased. She has had back pain over this same period and has been taking acetaminophen at doses at large as 650 mg four times daily, with her dose varying based on her symptoms. You recall a potential interaction and wonder if (1) her acetaminophen use is contributing to her loss of INR control, and (2) does this interaction place her at increased risk of warfarin-related complications?

  7. Initiation of exemestane in two warfarin-treated patients leading to elevation and variability of INR.

    Science.gov (United States)

    Dush, Aaron; Williams, Abby; Mangini, Neha; Klaczak, Kendra

    2016-04-01

    Aromatase inhibitors are sometimes chosen for adjuvant therapy in post-menopausal breast cancer patients with a history of venous thromboembolism over an antiestrogen due to the lower risk of venous thromboembolism associated with aromatase inhibitors compared to antiestrogens. We report two cases where patients on warfarin therapy had an increase in their international normalized ratio with the initiation of exemestane therapy. Initially, the patients also showed international normalized ratio variability possibly due to variable absorption of exemestane. We suggest patients being treated with warfarin and exemestane concomitantly need close monitoring and education in order to decrease the risk of adverse events that could be associated with this possible interaction. To our knowledge, there are no similar reported cases in the literature. © The Author(s) 2015.

  8. Treatments for Reversing Warfarin Anticoagulation in Patients with Acute Intracranial Hemorrhage: A Structured Literature Review

    Science.gov (United States)

    2011-07-08

    CINAHL® Via EBSCOhost ®) for relevant reviews and articles as of December 2009. We identified no relevant reviews in the Cochrane Database . A search...of articles relevant to intracranial hemorrhage and warfarin and treatment in the emergency department was performed. Databases for PubMed, CINAHL...multiple database searches revealed 586 papers for review for possible inclusion. The final consensus of our comprehensive search strategy was a total

  9. THE INVASIVE DENTAL PROCEDURES IN PATIENTS TREATING WITH WARFARIN: POSSIBILITIES AND PROSPECTS FOR SAFETY

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    T. V. Kozlova

    2010-01-01

    Full Text Available Details of the management of patients receiving oral anticoagulants (vitamin K antagonists for a long time and needed in dental treatment are discussed. Assessment of bleeding and thromboembolism risk in the perioperative continuation or termination of warfarin therapy is shown. Potential of the local hemostatic agents is specified. Modifications of the patient dental health card are offered to prevent complications associated with blood clotting disorders.

  10. Clinical factors influencing normalization of prothrombin time after stopping warfarin: a retrospective cohort study

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    Zondag Michelle

    2008-10-01

    Full Text Available Abstract Background Anticoagulation with warfarin should be stopped 4–6 days before invasive procedures to avoid bleeding complications. Despite this routine, some patients still have high International Normalized Ratio (INR values on the day of surgery and the procedure may be cancelled. We sought to identify easily available clinical characteristics that may influence the rate of normalization of prothrombin time when warfarin is stopped before surgery or invasive procedures. Methods Clinical data were collected retrospectively from consecutive cases from two cohorts, who stopped warfarin 6 days before surgery. An INR value of 1.6 or higher on the day of surgery or requirement for reversal with vitamin K the day before surgery were criteria for slow return (S to normal INR. Results Of 202 patients, 14 (7% were classified as S. Eight of the S-patients required reversal with vitamin K one day before surgery and in another case surgery was cancelled due to high INR. Baseline INR was the only variable significantly associated with classification as S in stepwise logistic regression analysis (p = 0.003. The odds ratio for being in the normal group was 0.27 (95% confidence interval 0.12–0.62 for each unit baseline INR increased. The positive predictive value of baseline INR with a cut off at > 3.0 was only 15% and for INR > 3.5 it was 33%. Conclusion Baseline INR, but not the size of the maintenance dose, is associated with the rate of normalization of prothrombin time after stopping warfarin, but it has limited utility as predictor in clinical practice. Whenever normal hemostasis is considered crucial for the safety, the INR should be checked again before the invasive procedure.

  11. A review of a priori regression models for warfarin maintenance dose prediction.

    Science.gov (United States)

    Francis, Ben; Lane, Steven; Pirmohamed, Munir; Jorgensen, Andrea

    2014-01-01

    A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

  12. A review of a priori regression models for warfarin maintenance dose prediction.

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    Ben Francis

    Full Text Available A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

  13. Differences between warfarin and new oral anticoagulants in dental clinical practice

    OpenAIRE

    Miranda, M; MARTINEZ, L.S.; De Franco, R.; FORTE, V.; BARLATTANI, A.; BOLLERO, P.

    2016-01-01

    The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant – dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) – have...

  14. Dental extraction in patients on warfarin treatment: a series of 35 patients

    OpenAIRE

    Abdullah WA; Khalil H

    2014-01-01

    Walid Ahmed Abdullah,1,2 Hesham Khalil1 1Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Oral and Maxillofacial Surgery, College of Dentistry, Mansoura University, Mansoura, Egypt Background: Warfarin is one of the most common oral anticoagulants used to prevent thromboembolic episodes. The benefits of discontinuation of this drug before simple surgical procedures are not clear and this approach could b...

  15. Drug interaction as cause of spontaneously resolving epidural spinal hematoma on warfarin therapy

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    Amitabh Sagar

    2010-01-01

    Full Text Available We present a case of a 42-year-old male, an old case of deep vein thrombosis on warfarin and other drugs like quetiapine, aspirin, diclofenac sodium, fenofibrate, atorvastatin, propanolol and citalopram for concurrent illnesses, who presented with widespread mucocutaneous bleeding and epidural spinal hematoma. The epidural bleed presented clinically as a nontraumatic, rapidly improving myeloradiculopathy. Magnetic resonance imaging (MRI of the spine revealed an epidural hematoma at D12-L1 level. The case was managed conservatively due lack of neurosurgical facilities. The patient gained full neurological recovery on conservative management alone. This case highlights the problem of drug interaction on warfarin therapy and also an unusual spontaneous recovery of spinal hematoma. Our case was anticoagulated in the recommended therapeutic INR range of 2.2 to 2.4. Most of the similar cases reported in literature were also anticoagulated in the therapeutic range. Thus intraspinal hemorrhage is a rare but dangerous complication of anticoagulant therapy. It must be suspected in any patient on anticoagulant agents who complains of local or referred spinal pain associated with neurological deficits. Drug interactions with warfarin are common. High suspicion and immediate intervention are essential to prevent complications from intraspinal hemorrhage.

  16. Levels of acarboxy prothrombin (PIVKA-II) and coagulation factors in warfarin-treated patients.

    Science.gov (United States)

    Umeki, S; Umeki, Y

    1990-04-01

    PIVKA-II (protein induced by vitamin K absence or antagonists-II) was determined and compared with other coagulation factors in normal subjects and patients treated with the anticoagulant warfarin. In 18 (60%) of 30 patients treated with warfarin, PIVKA-II values were 1 microgram/ml or more, although they were less than 1 microgram/ml in all 39 normal subjects (100%). In patients treated with warfarin, values of prothrombin time and partial thromboplastin time were significantly higher than those in normal subjects. However, values of hepaplastintest (normotest) and thrombotest in the patients were greatly lower than those in normal subjects. There were no significant differences between bleeding time or plasma fibrinogen values in the patients and normal subjects. The values of PIVKA-II were inversely correlated (P less than 0.01) with those of hepaplastintest and thrombotest. The measurement of PIVKA-II in the plasma should be useful in detecting vitamin K-deficient status among haemorrhagic disorders.

  17. Differences between warfarin and new oral anticoagulants in dental clinical practice.

    Science.gov (United States)

    Miranda, M; Martinez, L S; Franco, R; Forte, V; Barlattani, A; Bollero, P

    2016-01-01

    The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant - dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) - have been approved for use in europe. Increasing the number of patients taking these drugs, it is important that the dentist knows these new oral anticoagulants, their indications and methods of action, in particular for the management of patients, who require invasive treatments. With regard to the management of the patient threated with the new oral anticoagulants (NAO), there have been new significant changes in the procedure compared to the one followed by patients treated with warfarin. This led to the development of new guidelines that the dentist has to follow in order to ensure a safe and appropriate dental treatment and reduce any postoperative complications. The aim of this work is to evaluate the effectiveness of the new oral anticoagulants compared to warfarin, especially in terms of risks of bleeding events and intra and postoperative complications, in patients requiring multiple dental extractions.

  18. Effect of carbamazepine initiation and discontinuation on antithrombotic control in a patient receiving warfarin: case report and review of the literature.

    Science.gov (United States)

    Parrish, Richard H; Pazdur, Danielle E; O'donnell, Philip J

    2006-11-01

    A 72-year-old Caucasian woman with paroxysmal atrial fibrillation had been taking warfarin therapy for 5 years with a stable international normalized ratio (INR). Her dentist then prescribed carbamazepine 200 mg/day to control facial nerve pain. At her next physician visit about 2 weeks after the start of the carbamazepine, the patient's INR had dropped from 3.3 to 1.3; she reported no contributing changes in her diet or warfarin dosage, nor had she taken other interacting drugs. Her warfarin dosage was increased, and the INR returned to the target range of 2.0-3.0 approximately 2 months later. The patient's INR remained stable for approximately 6 more months, until she had facial surgery. During that time, her warfarin was discontinued for 5 days, and the patient had stopped taking the carbamazepine because she had no pain. One month later, her INR increased from 2.2 to 3.6. She did not experience any thrombotic or hemorrhagic episodes. Warfarin undergoes hepatic metabolism through cytochrome P450 2C9, and carbamazepine induces this isoenzyme. Inducing warfarin metabolism necessitates an increase in the warfarin dosage to maintain the INR in the therapeutic target range. To our knowledge, this is the first report documenting the effect of the carbamazepine initiation and discontinuation in a patient receiving anticoagulation therapy with warfarin. In patients taking warfarin, clinicians should monitor the INR closely when carbamazepine is started or discontinued, or when either dosage is changed.

  19. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy.

    Science.gov (United States)

    Takada, Tappei; Yamanashi, Yoshihide; Konishi, Kentaro; Yamamoto, Takehito; Toyoda, Yu; Masuo, Yusuke; Yamamoto, Hideaki; Suzuki, Hiroshi

    2015-02-18

    Vitamin K (VK) is a micronutrient that facilitates blood coagulation. VK antagonists, such as warfarin, are used in the clinic to prevent thromboembolism. Because VK is not synthesized in the body, its intestinal absorption is crucial for maintaining whole-body VK levels. However, the molecular mechanism of this absorption is unclear. We demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In vitro studies using NPC1L1-overexpressing intestinal cells and in vivo studies with Npc1l1-knockout mice revealed that intestinal VK absorption is NPC1L1-dependent and inhibited by ezetimibe, an NPC1L1-selective inhibitor clinically used for dyslipidemia. In addition, in vivo pharmacological studies demonstrated that the coadministration of ezetimibe and warfarin caused a reduction in hepatic VK levels and enhanced the pharmacological effect of warfarin. Adverse events caused by the coadministration of ezetimibe and warfarin were rescued by oral VK supplementation, suggesting that the drug-drug interaction effects observed were the consequence of ezetimibe-mediated VK malabsorption. This mechanism was supported by a retrospective evaluation of clinical data showing that, in more than 85% of warfarin-treated patients, the anticoagulant activity was enhanced by cotreatment with ezetimibe. Our findings provide insight into the molecular mechanism of VK absorption. This new drug-drug interaction mechanism between ezetimibe (a cholesterol transport inhibitor) and warfarin (a VK antagonist and anticoagulant) could inform clinical care of patients on these medications, such as by altering the kinetics of essential, fat-soluble vitamins.

  20. Relationship Between Time in Therapeutic Range and Comparative Treatment Effect of Rivaroxaban and Warfarin: Results From the ROCKET AF Trial

    Science.gov (United States)

    Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Harrell, Frank E.; Singer, Daniel E.; Becker, Richard C.; Breithardt, Günter; Halperin, Jonathan L.; Hankey, Graeme J.; Berkowitz, Scott D.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Background Time in therapeutic range (TTR) is a standard quality measure of the use of warfarin. We assessed the relative effects of rivaroxaban versus warfarin at the level of trial center TTR (cTTR) since such analysis preserves randomized comparisons. Methods and Results TTR was calculated using the Rosendaal method, without exclusion of international normalized ratio (INR) values performed during warfarin initiation. Measurements during warfarin interruptions >7 days were excluded. INRs were performed via standardized finger‐stick point‐of‐care devices at least every 4 weeks. The primary efficacy endpoint (stroke or non‐central nervous system embolism) was examined by quartiles of cTTR and by cTTR as a continuous function. Centers with the highest cTTRs by quartile had lower‐risk patients as reflected by lower CHADS2 scores (P<0.0001) and a lower prevalence of prior stroke or transient ischemic attack (P<0.0001). Sites with higher cTTR were predominantly from North America and Western Europe. The treatment effect of rivaroxaban versus warfarin on the primary endpoint was consistent across a wide range of cTTRs (P value for interaction=0.71). The hazard of major and non‐major clinically relevant bleeding increased with cTTR (P for interaction=0.001), however, the estimated reduction by rivaroxaban compared with warfarin in the hazard of intracranial hemorrhage was preserved across a wide range of threshold cTTR values. Conclusions The treatment effect of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism is consistent regardless of cTTR. PMID:24755148

  1. Serious Bleeding Events due to Warfarin and Antibiotic Co-prescription In a Cohort of Veterans

    Science.gov (United States)

    Lane, Michael A.; Zeringue, Angelique; McDonald, Jay R.

    2014-01-01

    Background Antibiotics may interact with warfarin, increasing the risk for significant bleeding events. Methods Retrospective cohort study of veterans prescribed warfarin for ≥ 30 days without interruption through the VA between October 1, 2002 and September 1, 2008. Antibiotics considered to be high-risk for interaction with warfarin include: trimethoprim/sulfamethoxazole (TMP/SMX), ciprofloxacin, levofloxacin, metronidazole, fluiconazole, azithromycin, and clarithromycin. Low-risk antibiotics include: clindamycin and cephalexin. Risk of bleeding event within 30 days of antibiotic exposure was measured using Cox proportional hazards regression, adjusted for demographic characteristics, comorbid conditions and receipt of other medications interacting with warfarin. Results A total of 22,272 patients met inclusion criteria with 14,078 and 8,194 receiving high- and low-risk antibiotics, respectively. There were 93 and 36 bleeding events in the high- and low-risk groups, respectively. Receipt of a high-risk antibiotic (HR 1.48, 95% CI 1.00-2.19) and azithromycin (HR 1.93, 95% CI 1.13-3.30) were associated with increased risk of bleeding as a primary diagnosis. TMP/SMX (HR 2.09, 95% CI 1.45-3.02), ciprofloxacin (HR 1.87, 95% CI 1.42-2.50), levofloxacin (HR 1.77, 95% CI 1.22-2.50), azithromycin (HR 1.64, 95% CI 1.16-2.33), and clarithromycin (HR 2.40, 95% CI 1.16-4.94) were associated with serious bleeding as a primary or secondary diagnosis. INR alterations were common; 9.7% of patients prescribed fluconazole had INR value >6. Patients who had INR performed 3-14 days of co-prescription were at a decrease risk of serious bleeding (HR 0.61, 95% CI 0.42-0.88). Conclusions Warfarin users who are prescribed high-risk antibiotics are at higher risk for serious bleeding events. Early INR evaluation may mitigate this risk. PMID:24657899

  2. Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: a meta-analysis.

    Science.gov (United States)

    Hassouna, Ahmed; Allam, Hemat

    2014-06-01

    The continuation of warfarin throughout pregnancy in patients with a mechanical valve prosthesis is a valid anticoagulation regimen, provided that warfarin dose does not exceed 5 mg/day. Two decades after being introduced, the efficacy and safety of this regimen merit evaluation. We performed a systematic review for cases published between January 1991 and January 2013. We compiled our prospective data on 55 pregnancies and calculated pooled estimates (95% confidence interval) of adverse foetal and maternal outcomes. Events were expressed as proportions of total pregnancies, except embryopathy and maternal death, which were related to the number of live births and number of patients, respectively. There were 494 eligible pregnancies reported in 11 studies. The rate of embryopathy was 0.9% (0.4-2.4%) and most of the 13.4% (8.4-24.7%) foetal losses were due to the 12.8% (7.7-22.7%) rate of spontaneous abortion. No maternal mortality was encountered (0-1.3%) but 0.6% (0.3-2%) prosthetic valve thrombosis, 1.8% (1.1-3.6%) total thromboembolic events and 3.4% (2-5.1%) major maternal bleeding events were recorded. Foetal loss, spontaneous abortions and foetal embryopathy dropped to 8.1% (2.9-13.7%), 7.3% (3.1-11.8%) and 0.6% (0.1-2.1%) among the 344 pregnancies (69.6%) observed in the 6 prospective studies (54.5%). Prosthetic valve thrombosis (0.6%; 01-2%), total thromboembolic (2.3%; 1.2-4.6%) and major bleeding events (2.9%; 1.8-6%) remained comparable with overall results. Foetal embryopathy and prosthetic valve thrombosis were not robust on sensitivity analysis, regardless of the study design. A prospective subgroup of 96 patients (19.4%) received smaller warfarin dose, through targeting a lower international normalized ratio (INR) between 1.5 and 2.5. The associated rate of foetal loss (2.1%; 0.5-6.9%) was significantly lower than that observed in the remaining patients targeting a higher INR between 2.5 and 3.5 (16.1%; 13.1-34.4%). Adverse maternal outcomes were

  3. Association of Proton Pump Inhibitors With Reduced Risk of Warfarin-Related Serious Upper Gastrointestinal Bleeding.

    Science.gov (United States)

    Ray, Wayne A; Chung, Cecilia P; Murray, Katherine T; Smalley, Walter E; Daugherty, James R; Dupont, William D; Stein, C Michael

    2016-12-01

    Proton pump inhibitors (PPIs) might reduce the risk of serious warfarin-related upper gastrointestinal bleeding, but the evidence of their efficacy for this indication is limited. A gastroprotective effect of PPIs would be particularly important for patients who take warfarin with antiplatelet drugs or nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), which further increase the risk of gastrointestinal bleeding. This retrospective cohort study of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample identified 97,430 new episodes of warfarin treatment with 75,720 person-years of follow-up. The study end points were hospitalizations for upper gastrointestinal bleeding potentially preventable by PPIs and for bleeding at other sites. Patients who took warfarin without PPI co-therapy had 119 hospitalizations for upper gastrointestinal bleeding per 10,000 person-years of treatment. The risk decreased by 24% among patients who received PPI co-therapy (adjusted hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63-0.91). There was no significant reduction in the risk of other gastrointestinal bleeding hospitalizations (HR, 1.07; 95% CI, 0.94-1.22) or non-gastrointestinal bleeding hospitalizations (HR, 0.98; 95% CI, 0.84-1.15) in this group. Among patients concurrently using antiplatelet drugs or NSAIDs, those without PPI co-therapy had 284 upper gastrointestinal bleeding hospitalizations per 10,000 person-years of warfarin treatment. The risk decreased by 45% (HR, 0.55; 95% CI, 0.39-0.77) with PPI co-therapy. PPI co-therapy had no significant protective effect for warfarin patients not using antiplatelet drugs or NSAIDs (HR, 0.86; 95% CI, 0.70-1.06). Findings were similar in both study populations. In an analysis of patients beginning warfarin treatment in Tennessee Medicaid and the 5% National Medicare Sample, PPI co-therapy was associated with reduced risk of warfarin-related upper gastrointestinal bleeding; the

  4. Raman spectroscopy as a complementary tool to assess the content uniformity of dosage units in break-scored warfarin tablets.

    Science.gov (United States)

    Arruabarrena, J; Coello, J; Maspoch, S

    2014-04-25

    Due to the side effects of overdosing, the therapeutic dose of warfarin preparations must be very strictly controlled. In order to make it easier for the patient to take the required dose, two different strategies can be followed: The medicine can be commercialized in different dosages and/or tablets can be scored in order to make them easy to split. The splitting of the tablets introduces the question of how to control that the fractions contain the desirable amount of warfarin. The regulations regarding the content uniformity of dosage unit for scored tablets have changed considerably in the last 10 years, and they are still evolving. Warfarin is commercialized under the trademark of Aldocumar in four different preparations, containing 1, 3, 5 and 10 mg sodium warfarin per tablet. All these tablets are also scored, thus suggesting the possibility of splitting. A quantitative Raman method has been developed for the determination of warfarin in tablets and in the potential fragments, taking into account the score lines on the tablet surface. This method is suggested as an auxiliary procedure to verify the uniformity of API distribution in dividable tablets. A combination of a second derivative and standard normal variate (SNV) was used as spectral pre-treatments, and partial least squares (PLS) as the regression algorithm. The relative standard deviation in API content among portions was found to be less than 5%. An HPLC procedure has been used as a reference analytical method.

  5. The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

    Directory of Open Access Journals (Sweden)

    Agustinus Wijaya

    2012-05-01

    Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

  6. Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Saffian, S M; Duffull, S B; Wright, Dfb

    2017-08-01

    There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I(2) = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  7. Introduction of a carbon paste electrode based on nickel carbide for investigation of interaction between warfarin and vitamin K1.

    Science.gov (United States)

    Torkashvand, Maryam; Gholivand, Mohammad Bagher; Taherpour, Avat Arman; Boochani, Arash; Akhtar, Arsalan

    2017-05-30

    In this paper a novel electrochemical sensor based on nickel carbide (Ni3C) nanoparticles as a new modifier was constructed. Ni3C nanoparticle was synthesized and characterized by scanning electron microscopy, X-ray diffraction and first-principles study. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) studies confirmed the electrode modification. Afterwards, the new electrode for the first time was used for interaction study between vitamin K1 and warfarin as an anticoagulant drug by differential pulse voltammetry. The adduct formation between the drug and vitamin K1 was improved by decreasing in anodic peak current of warfarin in the presence of different amounts of vitamin K1. The binding constant between warfarin and vitamin K1 was obtained by voltammetric and UV-vis and fluorescence spectroscopic methods. The molecular modeling method was also performed to explore the structural features and binding mechanism of warfarin to vitamin K1. The different aspects of modeling of vitamin K1 and warfarin and their adduct structures confirmed the adduct formation by hydrogen bonding. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Raunsø, Jakob; Selmer, Christian; Olesen, Jonas Bjerring;

    2012-01-01

    AIMS: It is presently unknown whether patients with atrial fibrillation (AF) are at increased risk of thrombo-embolic adverse events after interruption of warfarin treatment. The purpose of this study was to assess the risk and timing of thrombo-embolism after warfarin treatment interruption...

  9. TRial of an Educational intervention on patients' knowledge of Atrial fibrillation and anticoagulant therapy, INR control, and outcome of Treatment with warfarin (TREAT

    Directory of Open Access Journals (Sweden)

    Pattison Helen M

    2010-05-01

    Full Text Available Abstract Background Atrial fibrillation (AF patients with a high risk of stroke are recommended anticoagulation with warfarin. However, the benefit of warfarin is dependent upon time spent within the target therapeutic range (TTR of their international normalised ratio (INR (2.0 to 3.0. AF patients possess limited knowledge of their disease and warfarin treatment and this can impact on INR control. Education can improve patients' understanding of warfarin therapy and factors which affect INR control. Methods/Design Randomised controlled trial of an intensive educational intervention will consist of group sessions (between 2-8 patients containing standardised information about the risks and benefits associated with OAC therapy, lifestyle interactions and the importance of monitoring and control of their International Normalised Ratio (INR. Information will be presented within an 'expert-patient' focussed DVD, revised educational booklet and patient worksheets. 200 warfarin-naïve patients who are eligible for warfarin will be randomised to either the intervention or usual care groups. All patients must have ECG-documented AF and be eligible for warfarin (according to the NICE AF guidelines. Exclusion criteria include: aged Discussion More data is needed on the clinical benefit of educational intervention with AF patients receiving warfarin. Trial registration ISRCTN93952605

  10. Self-Learning, DVD-Based Education Versus Traditional Education Approaches to Improve the Safety of Warfarin Use Among Patients with Atrial Fibrillation

    OpenAIRE

    2015-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia that requires extensive medical and pharmaceutical management. The coagulation antagonist warfarin is commonly prescribed to reduce AF-associated stroke. Although warfarin effectively mediates thromboembolitic risk, its management is complex as many factors influence its therapeutic range including: genetics, diet, medication, and herbal and dietary supplement (HDS) interactions. Lack of patient knowledge regarding these factors contribu...

  11. Bleeding-Related Hospital Admissions and 30-Day Re-Admissions in Patients with Nonvalvular Atrial Fibrillation Treated with Dabigatran versus Warfarin

    DEFF Research Database (Denmark)

    Lau, Wallis C Y; Li, Xue; Wong, Ian C K

    2017-01-01

    BACKGROUND: Reducing 30-day hospital re-admission is a policy priority worldwide. Warfarin-related bleeding is among the most common cause of hospital admissions due to adverse drug events. Compared to warfarin, dabigatran achieve full anticoagulation effect more quickly following its initiation,...

  12. Telephone versus office-based management of warfarin: impact on international normalized ratios and outcomes.

    Science.gov (United States)

    Stoudenmire, Laura G; DeRemer, Christina E; Elewa, Hazem

    2014-08-01

    Studies have concluded that telephone-based management of warfarin is an effective alternative to in-office management. High rates of patient and physician satisfaction have been reported with telephone-based monitoring. Proposed benefits of telephone-based monitoring include time- and cost savings for patients and healthcare providers alike as well as increased access to care for those patients who have difficulty making in-office appointments. This study aimed to evaluate the impact of telephone versus office-based management of warfarin on extreme INR values. A retrospective cohort study was conducted to assess outcomes of patients receiving warfarin managed either by telephone or in-office appointments. The primary endpoint of the study was the frequency of extreme INR values, defined as an INR ≤1.5 or ≥4.5. A total of 110 patients were evaluated; subjects were distributed 2:1 between the in-office and telephone groups. Baseline characteristics were similar between groups. Subjects followed via telephone had a twofold increase in the incidence of extreme INR values compared to the patients followed in-office (15.18 vs. 7.98 %; p < 0.0001). Overall TTR was similar between groups (85.39 vs. 80.38 %, p = 0.1171). There was no difference between the two groups in the incidence of major bleeding events (2.67 vs. 0 %, p = 1.00), thromboembolic events (8 vs. 0 %, p = 0.1740), or hospitalizations related to anticoagulation therapy (6.67 vs. 0 %, p = 0.1758). Patients monitored via telephone had a higher incidence of extreme INR values than patients followed in-office, which may lead to an increased incidence of adverse outcomes in the long-term. Well-designed, prospective studies are needed to confirm such findings.

  13. Review of recently approved alternatives to anticoagulation with warfarin for emergency clinicians.

    Science.gov (United States)

    Brem, Elizabeth; Koyfman, Alex; Foran, Mark

    2013-07-01

    Dabigatran and rivaroxaban are novel anticoagulants that have been approved for the prevention of thromboembolic events in atrial fibrillation. These medications are attractive to both patients and clinicians, as, unlike warfarin, they do not require laboratory monitoring or dietary restrictions. However, they carry bleeding risks similar to that of warfarin and are without a reliable reversal agent. The objectives of this article are to 1) summarize the pivotal trials leading to the U.S. Food and Drug Administration approvals of dabigatran (Pradaxa; Boehringer Ingelheim, Ridgefield, CT) and rivaroxaban (Xarelto; Janssen Pharmaceuticals, Inc., Titusville, NJ); 2) present the limited data available regarding the management of bleeding patients on these agents; and 3) provide suggestions to guide emergency providers given the limited data. Dabigatran and rivaroxaban were approved based on large, non-inferiority trials comparing the new agents to warfarin with stroke or systemic embolism as the primary outcome. Traditional coagulation studies cannot be used to determine the degree of anti-coagulation produced by these agents. Fresh frozen plasma is unlikely to be effective in patients on these drugs who are acutely bleeding. Prothrombin complex concentrate can be considered in patients on rivaroxaban. Dabigatran is renally cleared, so dabigatran could be removed by hemodialysis. Theoretically, DDAVP (Sanofi-Aventis U.S. LLC, Bridgewater, NJ), aminocaproic acid, tranexamic acid, or recombinant activated factor VII could also be used in an attempt to control bleeding. There is a need for assays for the degree of anticoagulation produced by drugs such as dabigatran and rivaroxaban. Additionally, studies are needed to evaluate reversal agents that could be effective in the setting of acute bleeding. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Association Between Usual Vitamin K Intake and Anticoagulation in Patients Under Warfarin Therapy.

    Science.gov (United States)

    Park, Ji Na; Lee, Ji Sun; Noh, Min Young; Sung, Mi-Kyung

    2015-10-01

    This study aimed to explore the correlation between usual vitamin K intake and response to anticoagulant therapy among patients under warfarin therapy. We conducted a retrospective survey of patients (n = 50) on continuous warfarin therapy. Clinical information and laboratory parameters were sourced from medical records. Anticoagulant effect was evaluated by using the percent time in therapeutic range (TTR) and the coefficient of variation (CV) of International normalized ratio (INR). Dietary vitamin K intake was assessed using a semi-quantitative food frequency questionnaire that has been developed for the purpose of assessing dietary intake of vitamin K. A total of 50 patients aged between 21 and 87 years were included in the study. The mean vitamin K intake was 262.8 ± 165.2 µg/day. Study subjects were divided into tertiles according to their usual vitamin K intake. The proportion of men was significantly higher in second and third tertile than first tertile (p = 0.028). The mean percent TTR was 38.4 ± 28.4% and CV of INR was 31.8 ± 11.8%. Long-term warfarin therapy group (≥ 3 years) had a higher percentage of TTR as compared to the control group (vitamin K intake and percent TTR (p > 0.05). In conclusion, no significant association was observed between usual vitamin K intake and anticoagulant effects. Further studies are required to consider inter-individual variability of vitamin K intake. Development of assessment tools to measure inter-individual variability of vitamin K intake might be helpful.

  15. Aged garlic extract may be safe for patients on warfarin therapy.

    Science.gov (United States)

    Macan, Henry; Uykimpang, Rolando; Alconcel, Marcionila; Takasu, Junichiro; Razon, Rafael; Amagase, Harunobu; Niihara, Yutaka

    2006-03-01

    Garlic has been known to have antiplatelet properties. Because of the lack of major clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we decided to evaluate the safety of using garlic extract along with oral anticoagulation therapy. During this project we tested aged garlic extract (AGE), a commercial garlic preparation, with warfarin (Coumadin). Sixty-six (66) patients were screened for a double-blind, randomized, placebo-controlled pilot study. Fifty-two (52) patients were randomized for the project. Forty-eight patients (30 men and 18 women, with a mean age of 56+/-10 years) completed the study. Eighteen patients (14 before randomization, 4 after randomization) were dropped from the study. The study medication (AGE or placebo) was administered at a dose of 5 mL twice a day for 12 wk. Potential bleeding and thromboembolic episodes were monitored. There was no evidence of increased hemorrhage in either the placebo or the AGE group. Adverse events included headache, fatigue, colds, and dizziness. However, no significant difference was found in the incidence of these minor adverse events between the groups. Thus, the adverse events are unlikely to be attributable to AGE. The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy. Although the risk-benefit ratio of AGE use needs to be considered carefully when warfarin therapy is necessary, its positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications.

  16. Management of major bleedings during anticoagulant treatment with the oral direct thrombin inhibitor ximelagatran or warfarin.

    Science.gov (United States)

    Fernlöf, Gunilla; Sjöström, Britta M; Lindell, Klas M; Wall, Ulrika E

    2009-12-01

    Several new oral anticoagulants are currently investigated in phase III programmes, mainly with inhibition of factor Xa or thrombin as their pharmacological target. Advantages are expected with these new drugs compared with vitamin K antagonists, but one potential drawback is the lack of specific antidotes. During the clinical studies with ximelagatran, an oral direct thrombin inhibitor withdrawn due to hepatic side effects, investigators were instructed to manage bleedings with routine measures. We have retrospectively tried to assess whether this was sufficient or whether there was a need for reversal strategies. The study population consisted of patients with major bleedings in three long-term studies (104 ximelagatran, 155 warfarin). All individual patient narratives were reviewed with respect to management of the bleeding. Complementary data were retrieved from the data-based case report forms. Approximately, two of three of the patients in both groups were subject to some kind of treatment. One-third (1/3) in both groups had transfusions documented and/or received specific medication. Vitamin K was given more often to warfarin patients. Two ximelagatran patients received prothrombin complex (four-factor concentrate), but one was a patient with a severe hepatopathy suspected to be drug-induced. Overall, the case descriptions did not reveal any apparent differences in the course of events between groups. We found no indications that the lack of an antidote posed a clinical problem in patients treated with ximelagatran as compared with warfarin. The relatively short half-life of melagatran, the active metabolite of ximelagatran, may have contributed to these results.

  17. Is dabigatran considered a cost-effective alternative to warfarin treatment: a review of current economic evaluations worldwide.

    Science.gov (United States)

    Hesselbjerg, Louise Justesen; Pedersen, Heidi Sjoelund; Asmussen, Mikael Bergholdt; Petersen, Karin Dam

    2013-07-01

    Dabigatran was the first of a new generation of anticoagulation drugs for the indication of non-valvular atrial fibrillation (AF) to be approved. Evidence show that dabigatran 150 mg twice daily significantly reduces the risk of stroke and systemic embolism (RR = 0.65; p economic evaluations of these alternatives for healthcare professionals to include these findings in their decision-making. A systematic literature search identified 43 economic evaluations, of which 10 were included and evaluated according to the Consensus Health Economic Criteria list (CHEC-list) and the Oxford model. Six economic evaluations concluded that dabigatran was a cost-effective alternative to warfarin. One evaluation concluded the same except when quality in warfarin treatment was excellent, with a mean time in therapeutic range (TTR) > 73%. Three evaluations concluded that dabigatran was a cost-effective alternative to warfarin in patient sub-groups; TTR ≤ 64%, congestive heart failure, hypertension, age ≥ 75, diabetes mellitus, prior stroke or transient ischemic attack (CHADS2 score) ≥3, or a CHADS2 score = 2 unless international normalized ratio (INR) control was excellent, and with high risk of stroke or in a low-quality warfarin treatment. Dabigatran 110 mg twice daily was in general dominated by dabigatran 150 mg twice daily. The evaluations were not fully homogeneous, as some did not include loss of productivity, costs of dyspepsia, and annual costs of dabigatran patient management. In the majority of the economic evaluations, dabigatran is a cost-effective alternative to warfarin treatment. In some evaluations dabigatran is only cost-effective in sub-groups, such as patients with a low TTR-value in warfarin treatment and a CHADS2 score ≥2.

  18. Evaluation of an electronic warfarin nomogram for anticoagulation of hemodialysis patients

    Directory of Open Access Journals (Sweden)

    MacKay Elizabeth

    2011-09-01

    Full Text Available Abstract Background Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy. Methods Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units. Results Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods. Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%; post 95.6% (95% CI: 89.4% - 98.3%; p = 0.95; INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%; post 77.4% (95% CI: 72.0% - 82.0%; p = 0.20; and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%; post 66.8% (95% CI: 39.9% - 86.0%; p = 0.29. The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0 and post- (22.3, 95% CI: 18.4 - 26.1 (p = 0.003 period. There were 3 bleeding events in each of the periods. Conclusions An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram.

  19. RECURRENT STROKE IN THE WARFARIN VERSUS ASPIRIN IN REDUCED EJECTION FRACTION (WARCEF) TRIAL

    Science.gov (United States)

    Pullicino, Patrick M.; Qian, Min; Sacco, Ralph L.; Freudenberger, Ron; Graham, Susan; Teerlink, John R.; Mann, Douglas; Di Tullio, Marco R.; Ponikowski, Piotr; Lok, Dirk J.; Anker, Stefan D.; Lip, Gregory Y.H.; Estol, Conrado J.; Levin, Bruce; Mohr, J.P.; Thompson, John L. P.; Homma, Shunichi

    2014-01-01

    Background and Purpose WARCEF randomized 2305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0–3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. We here explore IIS rates in WARCEF patients with and without baseline stroke to look for risk factors for IIS and determine if a subgroup with an IIS rate high enough to give a clinically relevant stroke risk reduction can be identified. Methods We compared potential stroke risk factors between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS, by comparing IIS rates between different risk factors. For EF we tried cutoff points of 10%, 15% and 20%. 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. IIS rates per hundred patient years (/100PY) were calculated in patient groups with significant risk factors. Missing values were assigned the modal value. Results Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2048 (3.1%) without had IIS. IIS rate in patients with baseline stroke (2.37/100PY) was greater than patients without (0.89/100PY)(rate ratio 2.68, p<0.001). Fourteen of 219 (6.4%) patients with ejection fraction (EF)<15% and 70 of 2079 (3.4%) with EF ≥15% had IIS. In the multiple regression analysis stroke at baseline (p<0.001) and EF<15% vs. ≥15% (p=.005) remained significant predictors of IIS. IIS rate was 2.04/100PY in patients with EF<15% and 0.95/100PY in patients with EF ≥15% (p=0

  20. Fondaparinux vs warfarin for the treatment of unsuspected pulmonary embolism in cancer patients

    Directory of Open Access Journals (Sweden)

    Amato B

    2016-06-01

    Full Text Available Bruno Amato,1,2,* Rita Compagna,1,2,* Aldo Rocca,2 Tommaso Bianco,2 Marco Milone,2 Luigi Sivero,2 Gabriele Vigliotti,2 Maurizio Amato,2 Michele Danzi,2 Giovanni Aprea,2 Luca Gallelli,3,* Stefano de Franciscis,1,4,* Raffaele Serra1,4,* 1Interuniversity Center of Phlebolymphology, International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Viale Europa, Catanzaro, 2Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, 3Department of Health Sciences, 4Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy *These authors contributed equally to this work Introduction: In cancer patients, the chest computer tomography (CT can be used to identify asymptomatic pulmonary embolism (APE. In most cases, these patients are treated with anticoagulant drugs for at least 3 months. The American College of Physicians recommend treatment of these patients as patients with symptomatic pulmonary embolism. In this study, we evaluated and compared the efficacy and safety of fondaparinux vs warfarin in the prevention of unsuspected pulmonary embolism in patients with active cancer. Materials and methods: A prospective and parallel group study was performed on 64 cancer patients (29 males and 35 females with APE. A multidetector CT angiography with high spatial and temporal resolution and quality of arterial opacification was used to make the diagnosis. Lung scintigraphy was reserved to selected patients only. Patients were randomized to either the warfarin (Group A or the fondaparinux (Group B for 90 days. The first end point of efficacy was the persistence, reduction, or disappearance of thrombosis after 90 days. The second end point was the reappearance of thrombosis after 1 year. The first end point of safety was the development of major bleeding. Results: We enrolled 32 patients into each treatment group. We reached the

  1. Warfarin and Newer Agents: What the Oral Surgeon Needs to Know.

    Science.gov (United States)

    Steed, Martin B; Swanson, Matthew T

    2016-11-01

    The new direct oral anticoagulants-dabigatran etexilate, rivaroxaban, and apixaban- have predictable pharmacokinetic and pharmacodynamic profiles and are alternatives to warfarin. However, many surgeons are wary of these drugs, as there is limited evidence on how to manage bleeding in patients taking them, and only recently has a specific antidote been developed to reverse their anticoagulant effect. Management of the newer agents requires careful adherence to primary measures of bleeding care, knowledge of their mechanism of action, and familiarity with the unapproved and untested reversal strategies that may be required in patients with life-threatening bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

    DEFF Research Database (Denmark)

    Snygg-Martin, U; Rasmussen, Rasmus Vedby; Hassager, C;

    2011-01-01

    Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective...... factors for CVC, while warfarin on admission (aOR 0.26, 95% CI 0.07-0.94), history of congestive heart failure (adjusted OR 0.22, 95% CI 0.1-0.52) and previous endocarditis (aOR 0.1, 95% CI 0.01-0.79) correlated with lower CVC frequency....

  3. Outcomes of Temporary Interruption of Rivaroxaban Compared With Warfarin in Patients With Nonvalvular Atrial Fibrillation

    Science.gov (United States)

    Sherwood, Matthew W.; Douketis, James D.; Patel, Manesh R.; Piccini, Jonathan P.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Spyropoulos, Alex C.; Hankey, Graeme J.; Singer, Daniel E.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.; Becker, Richard C.

    2014-01-01

    Background During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. Methods and Results In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non–central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3–30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36–1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80–2.00]; P=0.32). Conclusions TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal

  4. Diagnosis and treatment of warfarin resistance%华法林抵抗的诊断及处理

    Institute of Scientific and Technical Information of China (English)

    谭胜蓝; 周新民; 李智; 张伟; 刘昭前; 周宏灏

    2013-01-01

    华法林抵抗指少数患者需服用显著高于常规剂量华法林才能达到目标国际标准化比值(international normalized ratio,INR)治疗范围,甚至无法达到目标INR的现象.华法林抵抗可分为遗传性抵抗和获得性抵抗两类,或分为药代动力学抵抗和药效动力学抵抗两类.临床上确诊华法林抵抗后,应尽快找出抵抗原因,对因治疗.患者依从性差、遗传变异、服用导致华法林吸收减少或清除加快的药物、摄人富含维生素K的饮食等是导致华法林抵抗最常见的原因.教育患者用药知识、增加华法林剂量或换用其他抗凝药可有效避免华法林抵抗.%Warfarin resistance is a phenomenon that patients need to take much higher than normally prescribed dosage of warfarin to maintain the target therapeutic international normalized ratio (INR) range, or even fail to reach the target INR. Warfarin resistance can be categorized in etiologic terms as hereditary vs acquired, or in pharmacologic terms as pharmacokinetic vs pharmacodynamic. Once warfarin resistance is diagnosed, the type of resistance should be determined as soon as possible so that treatment could be oriented toward the causes. Poor compliance, genetic mutations, concurrent medications that could decrease the absorption or increase the clearance of warfarin, and consumption of diet rich in vitamin K are the major reasons for warfarin resistance. Educating patients, increasing warfarin dosage and switching to other anticoagulants would be effective for warfarin resistance.

  5. Bleeding complications associated with warfarin treatment in ischemic stroke patients with atrial fibrillation: a population-based cohort study

    Science.gov (United States)

    Seet, Raymond CS; Rabinstein, Alejandro A; Christianson, Teresa JH; Petty, George W; Brown, Robert D

    2013-01-01

    Background Bleeding events are the major obstacle to the widespread use of warfarin for secondary stroke prevention. Previous studies have not examined the use of risk stratification scores to estimate lifetime bleeding risk associated with warfarin treatment in a population-based setting. The purpose of this study is to determine the lifetime risk of bleeding events in ischemic stroke patients with atrial fibrillation (AF) undergoing warfarin treatment in a population-based cohort and to evaluate the use of bleeding risk scores to identify patients at high-risk for lifetime bleeding events. Methods The resources of the Rochester Epidemiology Project Medical Linkage System were used to identify acute ischemic stroke patients with atrial fibrillation undergoing warfarin treatment for secondary stroke prevention from 1980 to 1994. Medical information for patients seen at Mayo Clinic and at Olmsted Medical Center were used to retrospectively risk-stratify stroke patients according to bleeding risk scores (including the HAS-BLED and HEMORR2HAGES scores) prior to warfarin initiation. These scores were reassessed one and five years later, and compared with lifetime bleeding events. Results One hundred patients (mean age, 79.3 years; 68% women) were studied. Ninety-nine patients were followed to death. Major bleeding events occurred in 41 patients at a median of 19 months following warfarin initiation. Patients with a history of hemorrhage before warfarin treatment were more likely to develop major hemorrhage (15% vs 3%, p=0.04). Patients with baseline HAS-BLED scores ≥2 had a higher lifetime risk of major bleeding events compared with those with scores ≤1 (53% vs 7%, pbleeding events compared with those with scores ≤1 (52% vs 16%, p=0.03). Patients with an increase in the HAS-BLED and HEMORR2HAGES scores during follow-up had a higher remaining lifetime risk of major bleeding events compared to those with no change. Conclusions Our findings indicate high lifetime

  6. Dentists' approach to patients on anti-platelet agents and warfarin: a survey of practice.

    LENUS (Irish Health Repository)

    Murphy, James

    2010-04-23

    In everyday practice, dentists are confronted with the dilemma of patients on anti-platelet agents and warfarin who require invasive dental procedures and, more pertinently, dental extractions. There may be a divergence of opinion among dentists regarding how they manage these patients. AIMS: To assess general dental practitioners\\' approach to the management of patients taking anti-platelet agents and\\/or warfarin who are undergoing invasive dental procedures. METHODS AND DATA: A semi-structured questionnaire was designed to survey general dental practitioners in a large Irish urban area. RESULTS: A response rate of 89% was achieved in a study population of 54 general dental practitioners. A total of 25% of respondents who carry out extractions on warfarinised patients do not check the INR prior to invasive dental procedures. Some 90% of respondents stop anti-platelet agents prior to extractions. CONCLUSIONS: A significant proportion of respondents fail to check warfarinised patients\\' INR prior to invasive dental procedures. Furthermore, a trend of stopping anti-platelet agents was noted, which is in contrast with current recommendations in the dental literature. Certain practices in this small study population proved alarming and highlight the need for improved awareness of current guidelines. A further large-scale study may be justified, as variation in practice may have clinical and medico-legal repercussions.

  7. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.

    Science.gov (United States)

    Schurgers, Leon J; Spronk, Henri M H; Soute, Berry A M; Schiffers, Paul M; DeMey, Jo G R; Vermeer, Cees

    2007-04-01

    Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.

  8. Intramural duodenal hematoma as a complication of therapy with Warfarin: a case report and literature review; Hematoma intramural duodenal como complicacao de terapia anticoagulante com Warfarin: relato de caso e revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Faria, Juliano [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Diagnostico por Imagem]. E-mail: drjuliano@uol.com.br; Pessoa, Roberta; Hudson, Marcelo; Vitoi, Silvio; Villela, Ovidio; Torres, Jose; Paula, Mara Delgado [Hospital Marcio Cunha, Ipatinga, MG (Brazil). Servico de Diagnostico por Imagem; Bemvindo, Aloisio [Hospital Marcio Cunha, Ipatinga, MG (Brazil). Servico de Terapia Intensiva

    2004-12-01

    We report a case of a patient receiving chronic oral anticoagulant therapy with Warfarin who presented with acute intestinal obstruction. Computed tomography showed intramural duodenal hematoma. Treatment was conservative with correction of the coagulation parameters and observation. This case exemplifies the usefulness of conservative therapy and computed tomography in patients with acute small bowel obstruction receiving anticoagulant therapy. (author)

  9. Pharmacogenomics of warfarin and its rational use%华法林的药物基因组学及其合理应用

    Institute of Scientific and Technical Information of China (English)

    娄莹; 李一石

    2011-01-01

    华法林为香豆素类抗凝血药,广泛用于防治血栓栓塞性疾病.华法林治疗窗窄,剂量个体差异大,临床应用中易出现出血合并症.近年研究表明,华法林个体剂量差异与影响华法林代谢和作用的多个基因多态性如CYP2C9、VKORC等有关.本文回顾华法林的药物基因组学研究进展,为临床合理应用华法林提供参考.%Warfarin is a coumarin anticoagulant widely used in the treatment and prevention of thrombo-embolic disorders.Warfarin has narrow therapeutic window and individual differences in dose, and hemorrhagic complications may occur in clinical use of warfarin.Recent studies indicate that the individual difference in warfarin dose is associated with gene polymorphisms influencing metabolism and action of warfarin such as CYP2C9,VKORC, and so on.The paper reviews the progress of the pharmacogenomics of Warfarin in order to provide a reference for rational use of warfarin in clinical practice.

  10. Dietary Vitamin K intake and anticoagulation control during the initiation phase of warfarin therapy: A prospective cohort study

    Science.gov (United States)

    The effect of varying levels of dietary vitamin K intake on therapeutic International Normalized Ratio (INR) values among patients starting warfarin therapy has not been well studied. We performed a prospective cohort study among 282 patients to explore the independent associations between usual in...

  11. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V

    DEFF Research Database (Denmark)

    White, Harvey D; Gruber, Michael; Feyzi, Jan;

    2007-01-01

    BACKGROUND: Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE) ...

  12. Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study.

    Science.gov (United States)

    Xu, Yan; Schulman, Sam; Dowlatshahi, Dar; Holbrook, Anne M; Simpson, Christopher S; Shepherd, Lois E; Wells, Philip S; Giulivi, Antonio; Gomes, Tara; Mamdani, Muhammad; Khuu, Wayne; Frymire, Eliot; Johnson, Ana P

    2017-07-01

    Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03). In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Quantification of Warfarin in Dried Rat Plasma Spots by High-Performance Liquid Chromatography with Tandem Mass Spectrometry

    Science.gov (United States)

    2016-01-01

    This paper presents the development and validation of a novel method for quantification of the oral anticoagulant drug warfarin in dried plasma spots (DPS) by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Blood plasma was chosen as a biological fluid to preclude the influence of the hematocrit on the results of the analysis. A 30 μL sample of rat plasma was placed onto Whatman 903 Protein Saver Card and was allowed to dry. A single DPS is sufficient for preparing eight 3.2 mm discs, each containing approximately 1.5–1.6 μL of plasma. Warfarin extraction from one 3.2 mm disc was carried out by adding 200 μL of the acetonitrile : water mixture (1 : 1, v/v) containing 10 mM NH4COOH (pH 4.0), with incubation on a shaker at 1000 rpm for 1 h at 25°C. After chromatographic separation, warfarin and coumachlor (an internal standard) were measured using negative-ion multiple-reaction monitoring with ion transitions m/z 307 → 161 for warfarin and m/z 341 → 161 for the internal standard. The working range of this method is 10–10,000 ng/mL. Within this range, intra- and interday variability of precision and accuracy was <13% and recovery was 82–99%. The results indicate that the new method requires only small plasma samples and may be useful for pharmacokinetic research on warfarin. PMID:28058133

  14. Best strategies for patient education about anticoagulation with warfarin: a systematic review

    Directory of Open Access Journals (Sweden)

    Singh Sonal

    2008-02-01

    Full Text Available Abstract Background Patient education is an essential component in quality management of the anticoagulated patient. Because it is time consuming for clinicians and overwhelming for patients, education of the anticoagulated patient is often neglected. We surveyed the medical literature in order to identify the best patient education strategies. Methods Study Selection: Two reviewers independently searched the MEDLINE and Google Scholar databases (last search March 2007 using the terms "warfarin" or "anticoagulation", and "patient education". The initial search identified 206 citations, A total of 166 citations were excluded because patients were of pediatric age (4, the article was not related to patient education (48, did not contain original data or inadequate program description (141, was focused solely on patient self-testing (1, was a duplicate citation (3, the article was judged otherwise irrelevant (44, or no abstract was available (25. Data Extraction: Clinical setting, study design, group size, content source, time and personnel involved, educational strategy and domains, measures of knowledge retention. Results Data Synthesis: A total of 32 articles were ultimately used for data extraction. Thirteen articles adequately described features of the educational strategy. Five programs used a nurse or pharmacist, 4 used a physician, and 2 studies used other personnel/vehicles (lay educators (1, videotapes (1. The duration of the educational intervention ranged from 1 to 10 sessions. Patient group size most often averaged 3 to 5 patients but ranged from as low as 1 patient to as much as 11 patients. Although 12 articles offered information about education content, the wording and lack of detail in the description made it too difficult to accurately assign categories of education topics and to compare articles with one another. For the 17 articles that reported measures of patient knowledge, 5 of the 17 sites where the surveys were

  15. Emergency department ultrasound diagnosis of spontaneous iliopsoas haemorrhage in a patient on warfarin.

    Science.gov (United States)

    Sharma, Devesh; Saker, Ramy; Govind, Abha

    2013-11-15

    A 87-year-old man presented to the emergency department (ED) with right-sided abdominal and thigh pain which had been present for the last 3 days and was getting worse. He had been diagnosed with a deep venous thrombosis of the left common femoral and superficial veins 10 days previously and had been discharged on a loading dose of warfarin and low-molecular weight heparin (dalteparin) injections. Despite his international normalised ratio being only 2.4, an ED ultrasound showed an unusual mass in the right iliac fossa, partly cystic and partly solid. A CT scan was performed which showed the lesion was a haematoma in the right iliopsoas muscle mass.

  16. An in vivo strategy to counteract post-administration anticoagulant activity of azido-Warfarin

    Science.gov (United States)

    Ursuegui, Sylvain; Recher, Marion; Krężel, Wojciech; Wagner, Alain

    2017-05-01

    Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent. In this strategy, the new molecule formed by reaction of the drug and the antidote is deprived of biological activity and prone to fast renal clearance. This `Click & Clear' approach lays ground for new strategies in designing drugs with switchable biophysical properties.

  17. Spectral assignments and structural studies of a warfarin derivative stereoselectively formed by tandem cyclization

    Science.gov (United States)

    Velayutham Pillai, M.; Rajeswari, K.; Vidhyasagar, T.

    2015-11-01

    The structural elucidation of a Mannich condensation product of rac-Warfarin with benzaldehyde and methyl amine was carried out using IR, Mass, 1H NMR, 13C NMR, 1H-1H COSY, 1H-13C COSY, DEPT-135, HMBC, NOESY spectra and single crystal X-ray diffraction. Formation of a new pyran ring via a tandem cyclization in the presence of methyl amine was observed. The optimized geometry and HOMO-LUMO energy gap along with other important physical parameters were found by Gaussian 09 program using HF 6-31G (d, p) and B3YLP/DFT 6-31G (d, p) level of theory. The preferred conformation of the piperidine ring in solution state was found to be chair from the NMR spectra. Single crystal X-ray diffraction and optimized geometry (by theoretical study) also confirms the chair conformation in the solid state.

  18. Bleeding events and associated factors in a cohort of adult patients taking warfarin in Sarawak, Malaysia.

    Science.gov (United States)

    Edwards, Frances; Arkell, Paul; Fong; Roberts, Lesley M; Gendy, David; Wong, Christina Siew-Hie; Ngu, Joanna Chee Yien; Tiong, Lee Len; Bibi, Faridha Mohd Salleh; Lai, Lana Yin Hui; Ong, Tiong Kiam; Abouyannis, Michael

    2014-01-01

    Evidence is emerging that rates of adverse events in patients taking warfarin may vary with ethnicity. This study investigated the rates of bleeds and thromboembolic events, the international normalised ratio (INR) status and the relationship between INR and bleeding events in Malaysia. Patients attending INR clinic at the Heart Centre, Sarawak General Hospital were enrolled on an ad hoc basis from May 2010 and followed up for 1 year. At each routine visit, INR was recorded and screening for bleeding or thromboembolism occurred. Variables relating to INR control were used as predictors of bleeds in logistic regression models. 125 patients contributed to 140 person-years of follow-up. The rates of major bleed, thromboembolic event and minor bleed per 100 person-years of follow-up were 1.4, 0.75 and 34.3. The median time at target range calculated using the Rosendaal method was 61.6% (IQR 44.6–74.1%). Of the out-of-range readings, 30.0% were below range and 15.4% were above. INR variability, (standard deviation of individuals’ mean INR), was the best predictor of bleeding events, with an odds ratio of 3.21 (95% CI 1.10–9.38). Low rates of both major bleeds and thromboembolic events were recorded, in addition to a substantial number of INR readings under the recommended target range. This may suggest that the recommended INR ranges may not represent the optimal warfarin intensity for this population and that a lower intensity of therapy, as observed in this cohort, could be beneficial in preventing adverse events.

  19. Racial background is a determinant of average warfarin dose required to maintain the INR between 2.0 and 3.0.

    Science.gov (United States)

    Blann, A; Hewitt, J; Siddiqui, F; Bareford, D

    1999-10-01

    Warfarin is a commonly used prophylactic agent for the prevention of thromboembolic disease. We hypothesized that racial background influenced warfarin dosage, and tested this by recording the international normalized ratio (INR) in 867 patients aged 40-90 routinely passing through our Anticoagulation Service whose target INR was 2-3. Mean (95% confidence interval) dose was 4.1 (4.0-4.2) mg/d in 737 Caucasians, 5.5 (4.9-6.1) mg/d in 72 Asians, and 6.7 (5. 8-7.6) mg/d in 58 Afro-Caribbeans (P warfarin use. Despite small numbers, we conclude that racial background, but not body mass index, is a determinant of warfarin dosage. The reasons for this could be genetic, cultural (diet related), or both.

  20. Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-γ agonist, on the pharmacokinetics and pharmacodynamics of warfarin

    Directory of Open Access Journals (Sweden)

    Jung JA

    2015-03-01

    Full Text Available Jin Ah Jung,1 Soo-Yun Lee,2 Tae-Eun Kim,3 Jung-Ryul Kim,1 Chin Kim,4 Wooseong Huh,1,5 Jae-Wook Ko1,2 1Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 3Department of Clinical Pharmacology, Konkuk University Medical Center, 4Clinical Research Team, CKD Pharmaceuticals, 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Aims: Lobeglitazone has been developed for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate potential drug–drug interactions between lobeglitazone and warfarin, an anticoagulant with a narrow therapeutic index.Methods: In this open-label, three-treatment, crossover study, 24 healthy male subjects were administered lobeglitazone (0.5 mg for 1–12 days with warfarin (25 mg on day 5 in one period. After a washout interval, subjects were administered warfarin (25 mg alone in the other period. Pharmacokinetics of R- and S-warfarin and lobeglitazone, as well as pharmacodynamics of warfarin, as measured by international normalized ratio (INR and factor VII activity, were assessed. Results: The geometric mean ratios (GMRs and 90% confidence intervals (CIs for area under the curve from time zero to the time of the last quantifiable concentration (AUClast for warfarin + lobeglitazone: warfarin alone were 1.0076 (90% CI: 0.9771, 1.0391 for R-warfarin and 0.9880 (90% CI: 0.9537, 1.0235 for S-warfarin. The maximum observed plasma concentration (Cmax values were 1.0167 (90% CI: 0.9507, 1.0872 for R-warfarin and 1.0028 (90% CI: 0.9518, 1.0992 for S-warfarin, both of which were contained in the interval 0.80–1.25. Lobeglitazone had no effect on the area under the effect–time curve from time 0 to 168 hours (AUEC of INR and factor VII activity, as demonstrated by the GMRs

  1. Extremely low warfarin dose in patients with genotypes of CYP2C9*3/*3 and VKORC1-1639A/A

    Institute of Scientific and Technical Information of China (English)

    GAO Lei; WANG Hong-juan; ZHAO Yu-sheng; LU Cai-yi; ZHANG Wen-zi; YIN Tong; HE Lei; LUO Jin; XU Bin; YANG Jie; ZHANG Yu-xiao; YANG Ting; LI Ke; TIAN Jin-wen

    2011-01-01

    Background Patients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin,and to have a greatly increased risk of bleeding.The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.Methods Demographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA.The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium.Results Both cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment,with target international normalized ratio (INR) 2 to 3.Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d.They needed more than 1 month to stabilize their anticoagulation.Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d.Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d.No concomitant medicine to increase or decrease the INR value was recorded for them.Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles-CYP2C9*3/*3 and VKORC1-1639 A/A.Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses.Conclusions Two Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin.The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes,as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.

  2. Exposure to Non-Therapeutic INR in a High Risk Cardiovascular Patient: Potential Hazard Reduction with Genotype-guided Warfarin (Coumadin®) Dosing

    Science.gov (United States)

    Rodríguez-Vélez, Rosángela; Ortiz-Rivera, Oscar J.; Bower, Bruce; Gorowski, Krystyna; Windemuth, Andreas; Villagra, David; Kocherla, Mohan; Seip, Richard L; D'Agostino, Darrin; Vergara, Cunegundo; Ruaño, Gualberto; Duconge, Jorge

    2013-01-01

    A case to illustrate the utility of genetic screening in warfarin (Coumadin®) management is reported. A 45 year-old woman of Puerto Rican ancestry was admitted to the emergency room twice within one month with chest pain. She was diagnosed with congestive heart failure, which was stabilized both times. At her second release, warfarin therapy was initiated at 5 mg/day to prevent thrombus formation and was lowered to 3.75 mg/day at day 7 by her primary physician. International Normalized Ratio (INR) test results in the follow-up period at days 1, 7, and 10 of warfarin therapy were 4.5, 6.5, and 7.3, respectively—far in excess of the therapeutic range, despite the lower dosage in effect from day 7 onward. the patient achieved target INR over the next 43 days after downward adjustment of the dose to a dose of 1.5 mg/day by trial and error. DNA-typing specific for the CYP2C9*2, *3, *4, *5, *6 alleles and seven variants in the VKORC1 gene, including the VKORC1-1639 G>A polymorphism, revealed the presence of combinatorial CYP2C9*2/*3 and VKORC1-1639 G/A genotypes in this patient. Entering the patient's demographic and genotype status data into independent algorithms available in the public domain to predict effective warfarin dose yielded predicted doses which ranged from 1.5 to 1.8 mg/day. Notably, the prediction of 1.5 mg/day, which was generated by the online resource www.warfarindosing.org, coincided with the patient's actual effective warfarin dose. We conclude that the rapid rise in INR observed upon the initiation of warfarin therapy and the final effective warfarin dose of 1.5 mg/day, are attributable in some part to the presence of two minor alleles in CYP2C9, which together significantly reduce warfarin metabolism. Warfarin genotyping can therefore inform the clinician of the predicted effective warfarin dose. the results highlight the potential for warfarin genetic testing to improve patient care. PMID:21261182

  3. Synthesis of conductive polymeric ionic liquid/Ni nanocomposite and its application to construct a nanostructure based electrochemical sensor for determination of warfarin in the presence of tramadol.

    Science.gov (United States)

    Molaakbari, Elaheh; Mostafavi, Ali; Beitollahi, Hadi; Tohidiyan, Zeinab

    2017-08-15

    In the current study, poly(MImEO8BS)-Ni nanocomposite was synthesized and applied to modify a glassy carbon electrode along with conductive polymeric ionic liquids. The electrochemical investigation of the modified electrode as well as its efficiency for voltammetric oxidation of warfarin is elucidated. The electrode was used to study the voltammetric oxidation of warfarin by employing cyclic voltammetry (CV), linear sweep voltammetry (LSV), chronoamperometry, and square wave voltammetry (SWV) as diagnostic techniques. It has been observed that warfarin oxidation at the surface of modified electrode occurs at a potential of about 230mV which is less positive than that of an unmodified glassy carbon electrode. SWV demonstrated a linear dynamic range from 1.0×10(-6) to 1.0×10(-4)M and a detection limit of 1.5×10(-7)M for warfarin. In addition, this modified electrode was utilized for simultaneous determination of warfarin and tramadol. Finally, the modified electrode was employed for determination of warfarin and tramadol in pharmaceutical compounds. Copyright © 2017. Published by Elsevier B.V.

  4. Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups

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    Antonio Gómez-Outes

    2013-01-01

    Full Text Available Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban have become available as an alternative to warfarin anticoagulation in non-valvular atrial fibrillation (NVAF. Methods. MEDLINE and CENTRAL, regulatory agencies websites, clinical trials registers and conference proceedings were searched to identify randomised controlled trials of NOAC versus warfarin in NVAF. Two investigators reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Relative risks (RR and 95% confidence intervals (CI were estimated using a random effect meta-analysis. Results. Three clinical trials in 50,578 patients were included. The risk of non-hemorrhagic stroke and systemic embolic events (SEE was similar with the NOAC and warfarin (RR=0.93; 95% CI=0.83–1.04, while the risk of intracranial bleeding (ICB with the NOAC was lower than with warfarin (RR = 0.46; 95% CI = 0.33–0.65. We found differences in the effect size on all strokes and SEE depending on geographic region as well as on non-hemorrhagic stroke, SEE, bleeding and mortality depending on time in therapeutic range. Conclusion. The NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke and SEE in the overall NVAF population, but are generally associated with a lower risk of ICB than warfarin.

  5. An electrochemical sensor for warfarin determination based on covalent immobilization of quantum dots onto carboxylated multiwalled carbon nanotubes and chitosan composite film modified electrode

    Energy Technology Data Exchange (ETDEWEB)

    Gholivand, Mohammad Bagher, E-mail: mbgholivand2013@gmail.com; Mohammadi-Behzad, Leila

    2015-12-01

    A method is described for the construction of a novel electrochemical warfarin sensor based on covalent immobilization of CdS-quantum dots (CdS-QDs) onto carboxylated multiwalled carbon nanotubes/chitosan (CS) composite film on the surface of a glassy carbon electrode. The CdS-QDs/CS/MWCNTs were characterized by field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infra-red (FTIR) spectroscopy, XRD analysis and electrochemical impedance spectroscopy (EIS). The sensor showed optimum anodic stripping response within 90 s at an accumulation potential of 0.75 V. The modified electrode was used to detect the concentration of warfarin with a wide linear range of 0.05–80 μM and a detection limit (S/N = 3) of 8.5 nM. The proposed sensor has good storage stability, repeatability and reproducibility and was successfully applied for the determination of warfarin in real samples such as urine, serum and milk. - Highlights: • A new sensitive sensor for warfarin determination was developed. • The sensor was constructed based on covalent immobilization of CdS-QDs on the chitosan/MWCNTs/GCE. • The parameters affecting the stripping analysis of warfarin were optimized. • The proposed sensor is used for trace determination of warfarin in urine, serum and milk.

  6. Natural history of bleeding and characteristics of early bleeders among warfarin initiators – a cohort study in Finland

    Directory of Open Access Journals (Sweden)

    Rikala M

    2016-02-01

    Full Text Available Maria Rikala,1 Helena Kastarinen,1,2 Pekka Tiittanen,1 Risto Huupponen,1,3 Maarit Jaana Korhonen1,4,5 1Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, 2Social Insurance Institution, Regional Office for Eastern and Northern Finland, Kuopio, 3Unit of Clinical Pharmacology, Turku University Hospital, 4Department of Public Health, University of Turku, Turku, Finland; 5Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, NC, USA Aims: The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. Patients and methods: Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012. We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. Results: The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%–2.7%, with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%–7.1%. In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9–17.1; during 180 days–7 years before initiation, HR =1.48, 95% CI 1.15–1.90, male sex (HR =1.32, 95% CI 1.10–1.57, older age (HR =1.13, 95% CI 1.04–1

  7. The occurrence of warfarin-related nephropathy and effects on renal and patient outcomes in korean patients.

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    Jung Nam An

    Full Text Available BACKGROUND: Warfarin-related nephropathy (WRN is a recently described disease entity, in which excessive warfarinization (international normalized ratio (INR >3.0 causes acute kidney injury. Previous reports regarding WRN included few Asian patients who might have differed from the western WRN patients in terms of genetic and environmental factors. METHODS: During the period of March 2003 to December 2011, the data about a total of 1297 patients who had serum creatinine (sCr level measured within 1 week after INR >3.0 and within 6 months before INR >3.0 was analyzed through the retrospective review of electronic medical records of a single tertiary hospital in Korea. RESULT: WRN developed in 19.3% of patients having excessive warfarinization. The incidence was higher in the chronic kidney disease (CKD group than the non-CKD group. The risk of WRN increased as the basal serum albumin level decreased and was strongly associated with highest quartile serum AST level at post INR elevation and the presence of congestive heart failure. But the presence of atrial fibrillation was protective against the development of WRN. Neither the presence of CKD nor basal estimated glomerular filtration rate (eGFR was an independent risk factor for WRN. Despite no difference in the basal sCr level, the sCr level was higher in patients with WRN than those without WRN after follow-up. The mortality rates were also higher in patients with WRN. CONCLUSIONS: WRN developed in 19.3% of patients having excessive warfarinization. A lower basal serum albumin, highest quartile serum AST level at post INR elevation, and congestive heart failure were associated with the occurrence of WRN. The development of WRN adversely affected renal and patient outcomes.

  8. Upper Gastrointestinal System Bleeding Associated with Mallory-Weiss Syndrome in a Patient with Prosthetic Mitral Valve Using Warfarin Sodium

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    Banu Şahin Yıldız

    2013-08-01

    Full Text Available Mallory-Weiss syndrome refers to bleeding from tears in the mucosa at the junction of the stomach and esophagus. Bleeding has been recognised as the major treatment-limiting complication in patients with prosthetic mitral valve using anticoagulant treatment. We report that upper gastrointestinal system bleeding associated with Mallory-Weiss syndrome in patient with prosthetic mitral valve using warfarin sodium.

  9. International Normalized Ratio Response Subsequent to Modest Increase in Vitamin K Intake in Patients Treated with Warfarin

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    Mona Foroughi

    2016-05-01

    Full Text Available Background: Warfarin is an effective oral anticoagulant which exert its effect by blocking the utilization of vitamin K. Warfarin therapy requires ongoing monitoring using the international normalized ratio (INR. In this study, effect of modest increase in vitamin K intake from vegetables on INR values was evaluated in warfarin treated patients.Methods: A single-center study involving 24 outpatients (mean age, 62 years with two last INR in therapeutic range in which INR variations was less than 0.5. Patients were selected based on their VKORC1 1639G→A polymorphism so that 8 patients from each of GG, AA or GA genotypes were recruited. Patients were asked to consume a vegetable mix (including lettuce, peeled cucumber and tomato containing approximately 100 µg vitamin K (divided in two meals, lunch and dinner daily for one week when INR response was measured.Results: Daily consumption of vegetable mix decreased patient’s INR from 2.43±0.51 to 2.08± 0.46 (P<0.001. INR value had a significant decrease in each VKORC1 genotypes (from 2.55± 0.55 to 2.21± 0.54 in GG, 2.35± 0.33 to 2.00± 0.25 in AA, and  2.39± 0.65 to 2.00± 0.25 in GA but the values did not differ between genotypes.Conclusions: Daily increase in vegetable salad containing approximately 100 µg, decreased INR of patients. Therefore, avoiding variation in consumption of foods with even moderate content of vitamin K could help to prevent INR fluctuations in warfarin treated patients.

  10. Mekanik Kalp Kapaklı Hastalarda Antikoagülan Kullanımı ve Warfarin Direnci

    OpenAIRE

    2015-01-01

    Objectives:  To evaluate the treatment choices applied to patients with mechanical heart valves who were determined as resistant to warfarin.Materials and Method: The study comprised 40 patients (22 male, 18 female; mean age 58.15 years) who had been fitted with mechanical heart valves and were under International Normalised Ratio (INR) monitoring between 2006 and 2014. Until the target level was achieved, INR monitoring was applied once a week and thereafter once a month. The INR target valu...

  11. Bleeding complications related to warfarin treatment: a descriptive register study from the anticoagulation clinic at Helsingborg Hospital.

    Science.gov (United States)

    Navgren, Monica; Forsblad, Johan; Wieloch, Mattias

    2014-07-01

    The most common indication for treatment with warfarin is the prevention of ischemic stroke in patients with atrial fibrillation. Time in therapeutic range (TTR) is an important tool to evaluate the quality of anticoagulation treatment. The aim of this study was to investigate the quality of treatment and the incidence of bleeding complications in patients on warfarin treatment treated by the anticoagulation clinic in Helsingborg. This is the first study that has specifically focused on the spontaneous reporting of bleeding complications in a real-world population. A total of 4,400 patients with a total of 8,394 patient years were registered, in the database Journalia AVK, during the time period November 1, 2007 to November 1, 2010. The mean age was 72 years. TTR was 73.3 % for the whole population. 421 patients suffered from haemorrhagic events. The frequency of major and fatal bleedings and intracranial haemorrhage (ICH) were 1.6, 0.2 and 0.5% per patient-year, respectively. A correlation between age and severe bleeding (major, fatal and ICH) (p = 0.003) was seen, but no correlation between gender and severe bleeding (p = 0.27). In 60 out of 455 bleeding events the complication had been reported to the anticoagulation clinic. At the anticoagulation clinic in Helsingborg the quality of warfarin treatment is good compared to previous results described in the literature, with regards to bleeding complications and efficacy. However, in our study, we confirm that the spontaneous reporting of bleeding complications related to warfarin is inadequate, and that review of patient records is needed to assure proper follow-up.

  12. Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus).

    Science.gov (United States)

    Uehara, Shotaro; Inoue, Takashi; Utoh, Masahiro; Toda, Akiko; Shimizu, Makiko; Uno, Yasuhiro; Sasaki, Erika; Yamazaki, Hiroshi

    2016-01-01

    1. Pharmacokinetics of human cytochrome P450 probes (caffeine, racemic warfarin, omeprazole, metoprolol and midazolam) composite, after single intravenous and oral administrations at doses of 0.20 and 1.0 mg kg(-1), respectively, to four male common marmosets were investigated. 2. The plasma concentrations of caffeine and warfarin decreased slowly in a monophasic manner but those of omeprazole, metoprolol and midazolam decreased extensively after intravenous and oral administrations, in a manner that approximated those as reported for pharmacokinetics in humans. 3. Bioavailabilities were ∼100% for caffeine and warfarin, but midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system. 4. These results suggest that common marmosets, despite their rapid clearance of some human P450 probe substrates, could be an experimental model for humans and that marmoset P450s have functional characteristics that differ from those of human and/or cynomolgus monkey P450s in some aspects, indicating their importance in modeling in P450-dependent drug metabolism studies in marmosets and of further studies.

  13. The interaction between vitamin K nutriture and warfarin administration in patients with bacterial overgrowth due to atrophic gastritis.

    Science.gov (United States)

    Camilo, M E; Paiva, S A; O'Brien, M E; Booth, S L; Davidson, K W; Sokoll, L J; Sadowski, J A; Russell, R M

    1998-01-01

    Atrophic gastritis patients have intestinal bacterial overgrowth which could produce menaquinones. The aim of this study was to evaluate the interaction between a diet low in phylloquinone and minidoses of warfarin in subjects with and without bacterial overgrowth. Subjects with atrophic gastritis (indicated by serum pepsinogen ratio) and healthy volunteers were studied while fed a restrictive phylloquinone diet and while receiving a minidose of warfarin. Coagulation times, serum osteocalcin, serum undercarboxylated osteocalcin, plasma phylloquinone, plasma K-epoxide, plasma undercarboxylated prothrombin (PIVKA)-II and urinary gamma-carboxyglutamic acid (Gla) were measured. At baseline, there were no differences between groups for any variable measured. Comparisons between baseline and post intervention in both groups, showed significant increases in circulating levels of K-epoxide, PIVKA II and undercarboxylated osteocalcin. However, no differences were observed when comparisons were made between groups. Our data do not support the hypothesis that bacterial synthesis of menaquinones in patients with bacterial overgrowth due to atrophic gastritis confers considerable resistance to the effect of warfarin.

  14. Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban

    Science.gov (United States)

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D; Hellkamp, Anne S; Piccini, Jonathan P; Lokhnygina, Yuliya; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Califf, Robert M; Fox, Keith A A; Patel, Manesh R

    2016-01-01

    Objective To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD). Methods Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis. Results Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31). Conclusions We found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD. Trial registration number NCT00403767; Post-results. PMID:26888572

  15. Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on the pharmacokinetics of oral contraceptives, warfarin, and digoxin in healthy participants.

    Science.gov (United States)

    Devineni, Damayanthi; Manitpisitkul, Prasarn; Vaccaro, Nicole; Bernard, Apexa; Skee, Donna; Mamidi, Rao N V S; Tian, Hong; Weiner, Sveta; Stieltjes, Hans; Sha, Sue; Rothenberg, Paul

    2015-01-01

    Drug-drug interactions between canagliflozin, a sodium glucose co-transporter 2 inhibitor approved for the management of type-2 diabetes mellitus, and an oral contraceptive (OC), warfarin, and digoxin were evaluated in three phase 1 studies in healthy participants. All studies were open-label; study 1 included a fixed-sequence design, and studies 2 and 3 used a crossover design. Regimens were: study 1: OC (levonorgestrel (150 μg) + ethinyl estradiol (30 μg))/day (day 1), canagliflozin 200 mg/day (days 4 - 8), and canagliflozin with OC (day 9); study 2: canagliflozin 300 mg/day (days 1 - 12) with warfarin 30 mg/day (day 6) in period 1, and only warfarin 30 mg/day (day 1) in period 2, or vice versa; study 3: digoxin alone (0.5 mg/day (day 1) + 0.25 mg/day (days 2 - 7)) in period 1, and with canagliflozin 300 mg/day (days 1 - 7) in period 2, or vice versa. Pharmacokinetics (PK) were assessed at prespecified intervals; OC: days 1 and 9, canagliflozin: days 8 - 9 (study 1); warfarin: days 6 (period 1) and 1 (period 2) (study 2); and digoxin: days 5 - 7 (periods 1 and 2) (study 3). Warfarin's pharmacodynamics (PD; International Normalized Ratio (INR)) was assessed on days 6 (period 1) and 1 (period 2). Canagliflozin increased the plasma exposure of OC (maximum plasma concentration (Cmax): 22%, area under the curve (AUC): 6%) and digoxin (Cmax: 36%, AUC: 20%); but did not alter warfarin'€™s PK and PD. No clinically relevant safety findings (including hypoglycemia) were noted. Canagliflozin can be coadministered with OC, warfarin, or digoxin without dose adjustments. All treatments were well-tolerated.

  16. Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

    Science.gov (United States)

    Kwon, Chang Hee; Kim, Minsu; Kim, Jun; Nam, Gi-Byoung; Choi, Kee-Joon; Kim, You-Ho

    2016-01-01

    Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asian octogenarian atrial fibrillation (AF) patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged ≥ 80 years with non-valvular AF who had taken either NOACs (148 cases, 50.5%) or warfarin (145 cases, 49.5%) were retrospectively reviewed. The efficacy outcome was the composite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years (172 patient-years with NOACs and 203 patient-years with warfarin). Patients on NOACs were slightly older (P = 0.006) and had slightly higher HAS-BLED scores (P = 0.034). The efficacy of both anticoagulants was high (1.16% for NOACs vs. 2.98% for warfarin per 100 patient-years, P = 0.46). The safety outcome was relatively high in both NOACs and warfarin groups (8.96% vs. 12.46%, P = 0.29). The efficacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin (0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34). Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population. PMID:27605936

  17. COMPARISON OF DIRECT COSTS OF DABIGATRAN AND WARFARIN THERAPY IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION DURING PREPARATION FOR ELECTIVE CARDIOVERSION IN THE REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    L. E. Kuvshinova

    2015-09-01

    Full Text Available Aim. To compare direct medical costs of dabigatran and warfarin therapy in patients with non-valvular atrial fibrillation (NVAF during preparation for elective cardioversion. Material and methods. An open non-randomized study was conducted to evaluate direct medical costs (cost of drug, cost of the international normalized ratio (INR adjust- ment in outpatient clinic, cost of visits to cardiologist. Patients (n=62 with persistent NVAF (AF paroxysm duration > 48 hours were enrolled. All of them requested medical as- sistance and were decided to perform an elective cardioversion. The patients received warfarin (n=32 or dabigatran (n=30. The patients of the both groups were similar in the main clinical characteristics and thromboembolic risk levels according to CHA2DS2-VASc scale.Results. Treatment duration before elective cardioversion was 21±2 and 30.5±4.5 days for dabigatran and warfarin groups, respectively (p<0.05. Average costs of visits to cardiologists were 3,720 and 744 RUB in warfarin and dabigatran groups, respectively (p<0.05, and drug costs were 53.63 and 1,172.01 RUB, respectively (p<0.05. The costs of laboratory INR monitoring were 3,058 RUB in warfarin group. Total costs per patient were 6,831.63 and 1,916.01 RUB in warfarin and dabigatran groups, respectively (p<0.05. Conclusion. In the real clinical practice in patients with NVAF dabigatran antithromboembolic therapy substantially reduces direct medical costs in comparison with warfarin ther- apy during preparation for elective cardioversion. Dabigatran therapy reduces time from the decision of elective cardioversion and antithromboembolic therapy start to car- dioversion performance.

  18. Increased PAC-1 expression among patients with multiple myeloma on concurrent thalidomide and warfarin.

    Science.gov (United States)

    Abdullah, Wan Z; Roshan, Tariq M; Hussin, Azlan; Zain, Wan S W Md; Abdullah, Dzarr

    2013-12-01

    Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P thalidomide is probably multifactorial and one of them is likely through platelet activation. Further study on the affected pathway/s in the platelet activation process would confirm the exact mechanism of thalidomide-induced thrombosis and potential extended usage of this drug in future.

  19. A case of post-irradiation lumbosacral radioculopathy successfully treated with corticosteroid and warfarin

    Energy Technology Data Exchange (ETDEWEB)

    Anezaki, Toshiharu; Harada, Takashi; Kawachi, Izumi; Sanpei, Kazuhiro; Soma, Yoshiaki; Tsuji, Shoji [Niigata Univ. (Japan). Brain Research Inst

    1999-08-01

    A 33-year-old man underwent post-operative radiation therapy for the left testicular anaplastic seminoma. One year later, the patient developed muscle weakness and sensory disturbance in the left lower extremity, and muscle weakness in the right lower extremity. MRI demonstrated linear and focal gadolinium (Gd) enhancement of the anterior portion of the lumbosacral roots within the cauda equina. The neurological symptoms improved after administration of corticosteroid and warfarin. Radiation myelopathy of this type was classified as ''selective anterior horn cell injury or amyotrophy'' by Reagan, and the site of the lesion was considered to be the lower motor neurons. However, based on the clinical and MRI findings, we proposed that the disease process was injury to the spinal nerve roots rather than the lower motor neurons. Recent neuropathological studies of this syndrome have demonstrated degeneration of the proximal spinal nerve roots. We consider that primary lesions of this syndrome occur in spinal nerve roots rather than in lower motor neurons, and ''lumbosacral radiculopathy'' is a more appropriate term for this condition. (author)

  20. Arthrofibrosis following total knee replacement; does therapeutic warfarin make a difference?

    Science.gov (United States)

    Walton, N P; Jahromi, I; Dobson, P J; Angel, K R; Lewis, P L; Campbell, D G

    2005-04-01

    Arthrofibrosis following total knee replacement (TKR) is a relatively common complication which results in a reduction in knee range of movement and patient dissatisfaction. A retrospective study examined the relationship between anticoagulation with therapeutic warfarin and rates of arthrofibrosis following TKR. Arthrofibrosis was defined as less than 80 degrees of knee flexion 6-8 weeks post-TKR. Patients were warfarinised if they had a history of thrombophilic tendencies or medical conditions necessitating anti-coagulation, rather than as routine thromboprophylaxis. All other patients received thromboprophylaxis using low molecular weight heparin. A total of 728 patients underwent 874 primary TKR between 1993 and 2002 in one centre, performed by four surgeons. Mean age was 68 years (range 48-89 years) and there were 483 female and 391 male knees. Eighty cases were warfarinised post-operatively (53 female, 27 male). Overall, 83 of 874 TKRs (9%) had arthrofibrosis (57 female, 26 male) requiring manipulation under anaesthetic (MUA). In the warfarinised group, 21 knees (26%) had an MUA (15 female, 6 male). This compared to 62 cases (8%) requiring MUA in the non-warfarinised group (42 female, 20 male). There was a statistically significant difference on Fisher's exact testing (Parthrofibrosis compared to prophylactic low molecular weight heparin and that patients should be counseled appropriately.

  1. Does the continuation of warfarin change management outcomes in epistaxis patients?

    Science.gov (United States)

    Bola, S; Marsh, R; Braggins, S; Potter, C; Hickey, S

    2016-03-01

    This study aimed to compare management, readmission rates and length of in-patient stay amongst warfarinised and non-warfarinised patients to ascertain future treatment protocols. A 12-month retrospective review was conducted of ENT epistaxis admissions. Admission details such as length of in-patient stay, clotting profile and management plan were recorded. Comparisons of management and outcome for warfarinised and non-warfarinised patients were made using the Fisher's exact paired t-test. Of 176 epistaxis patients admitted, 31 per cent were warfarinised, 18 per cent were on another form of anticoagulation or antiplatelet therapy, and 51 per cent were not on any medication that might impose a bleeding risk. The international normalised ratio at admission was high in 13 per cent of warfarinised patients; the remaining patients had therapeutic or sub-therapeutic international normalised ratios and so warfarin was continued. The mean in-patient stay was similar for all cohorts; however, warfarinised patients had a higher readmission rate. Warfarinised epistaxis patients may be safely managed without stopping their anticoagulation therapy, provided their international normalised ratio is at therapeutic or sub-therapeutic levels. By continuing regular anticoagulation therapy, warfarinised patients may be discharged without delay.

  2. Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

    Science.gov (United States)

    Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

    2015-11-10

    Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.

  3. Comparison of Dabigatran vs. Warfarin in Acute Vnous Thromboemboly: Systematic Review.

    Science.gov (United States)

    Ganji, Reza; Ala, Shahram; Aarabi, Mohsen; Baghery, Babak; Salehifar, Ebrahim

    2016-01-01

    Acute Venous Thromboembolism (VTE) is a common disease associated with the significant morbidity and mortality. We reviewed clinical outcomes systematically with Dabigatran as a direct oral anticoagulants (DOAC) for treatment of acute VTE. We used Ovide, PubMed, Cochrane (CENTRAL), EMBASE, Scopus, Science Direct, LILAC(for article written not English) and also Iranian database; Magiran, Isc, Iran Medex, Iran DOC, Doaj up to May 2014 to identify randomized clinical trials of Dabigatran compared with conventional treatment for VTE. Two investigators extracted data independently. Number of 5107 patients including two trails were selected. The risk of recurrent VTE was similar with the Dabigatran and standard treatment (Hazard Ratio, 95% confidence interval 1.09 (0.76-1.57). Dabigatran reduced the risk of minor bleeding in comparison with standard treatment; Warfarin (0.62) (0.50-0.76). Finally-in minor bleeding-the Dabigatran seemed as effective as, and probably safer than standard treatment of acute VTE. But in some aspects such as adherence to treatment, pregnant patient, impact on quality of life, new researches are needed to be clarified.

  4. [Hokusai-VTE: edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism].

    Science.gov (United States)

    Sprynger, M

    2013-10-01

    Currently venous thromboembolic disease (VTE), i.e. deep venous thrombosis and pulmonary embolism, remains a major cause of morbidity and mortality all around the world. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial heparin (5 days) followed by the oral Xa factor inhibitor edoxaban (60 mg once daily) may be an alternative to the standard therapy, i.e. heparin (5 days) followed by warfarin (INR of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic VTE. In patients with VTE, including pulmonary embolism with right ventricular dysfunction, treatment with heparin followed by oral edoxaban 60 mg once daily was non inferior to the standard treatment with respect to efficacy and superior with respect to bleeding (fewer fatal and intracranial bleeds, but no statistical significance regarding major bleeding). Reducing the dosage of edoxaban to 30 mg once daily is safe in case of renal impairment and low body weight.

  5. Solid-state (17)O NMR study of 2-acylbenzoic acids and warfarin.

    Science.gov (United States)

    Kong, Xianqi; Dai, Yizhe; Wu, Gang

    We report synthesis and solid-state (17)O NMR characterization of four site-specifically (17)O-labeled 2-acylbenzoic acids (2-RC(O)C6H4COOH) where R=H and CH3): 2-[3-(17)O]formylbenzoic acid, 2-[1,2-(17)O2]formylbenzoic acid, 2-[3-(17)O]acetylbenzoic acid, and 2-[1,2,3-(17)O3]acetylbenzoic acid. In the solid state, both 2-formyl- and 2-acetyl-benzoic acids exist as the cyclic phthalide form each containing a five-membered lactone ring and a cyclic hemiacetal/hemiketal group. Static and magic-angle-spinning (17)O NMR spectra were recorded at 14.1 and 21.1T for these compounds, from which the (17)O chemical shift and nuclear quadrupolar coupling tensors were determined for each oxygen site. These results represent the first time that (17)O NMR tensors are fully characterized for lactone, cyclic hemiacetal, and cyclic hemiketal functional groups. We also report solid-state (17)O NMR data for the cyclic hemiketal group an anticoagulant drug, warfarin. Experimental (17)O NMR tensors in these compounds were compared with computational results obtained with a periodic DFT code BAND. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Warfarin use and stroke, bleeding and mortality risk in patients with end stage renal disease and atrial fibrillation: a systematic review and meta-analysis.

    Science.gov (United States)

    Tan, Jingwen; Liu, Shuiqing; Segal, Jodi B; Alexander, G Caleb; McAdams-DeMarco, Mara

    2016-10-21

    Patients with end stage renal disease (ESRD), including stage 5 chronic kidney disease (CKD), hemodialysis (HD) and peritoneal dialysis (PD), are at high risk for stroke-related morbidity, mortality and bleeding. The overall risk/benefit balance of warfarin treatment among patients with ESRD and AF remains unclear. We systematically reviewed the associations of warfarin use and stroke outcome, bleeding outcome or mortality in patients with ESRD and AF. We conducted a comprehensive literature search in Feb 2016 using key words related to ESRD, AF and warfarin in PubMed, Embase and Cochrane Library without language restriction. We searched for randomized trials and observational studies that compared the use of warfarin with no treatment, aspirin or direct oral anticoagulants (DOACs), and reported quantitative risk estimates on these outcomes. Paired reviewers screened articles, collected data and performed qualitative assessment using the Cochrane Risk of Bias Assessment Tool for Non-randomized Studies of Interventions. We conducted meta-analyses using the random-effects model with the DerSimonian - Laird estimator and the Knapp-Hartung methods as appropriate. We identified 2709 references and included 20 observational cohort studies that examined stroke outcome, bleeding outcome and mortality associated with warfarin use in 56,146 patients with ESRD and AF. The pooled estimates from meta-analysis for the stroke outcome suggested that warfarin use was not associated with all-cause stroke (HR = 0.92, 95 % CI 0.74-1.16) or any stroke (HR = 1.01, 95 % CI 0.81-1.26), or ischemic stroke (HR = 0.80, 95 % CI 0.58-1.11) among patients with ESRD and AF. In contrast, warfarin use was associated with significantly increased risk of all-cause bleeding (HR = 1.21, 95 % CI 1.01-1.44), but not associated with major bleeding (HR = 1.18, 95 % CI 0.82-1.69) or gastrointestinal bleeding (HR = 1.19, 95 % CI 0.81-1.76) or any bleeding (HR = 1.21, 95

  7. Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban – an oral, direct Factor Xa inhibitor

    Directory of Open Access Journals (Sweden)

    Rolf eBurghaus

    2014-11-01

    Full Text Available The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2–3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.

  8. The Use of Fish Oil with Warfarin Does Not Significantly Affect either the International Normalised Ratio or Incidence of Adverse Events in Patients with Atrial Fibrillation and Deep Vein Thrombosis: A Retrospective Study

    Directory of Open Access Journals (Sweden)

    Rebecca Pryce

    2016-09-01

    Full Text Available Background: Warfarin is a leading anticoagulant in the management of atrial fibrillation (AF and deep vein thrombosis (DVT. Drug interactions influence the safety of warfarin use and while extensive literature exists regarding the effect on warfarin control and bleeding incidence with many medicines, there is little evidence on the influence of complementary medicines. The aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control and bleeding incidence in AF and DVT patients. Methods: A retrospective analysis was conducted utilising patient information from a large private pathology clinic. AF and DVT patients receiving long-term warfarin therapy (>30 days at the clinic and taking fish and krill oil supplements were eligible for study inclusion. Results: Of the 2081 patients assessed, a total of 573 warfarin users met the inclusion criteria with 145 patients in the fish and krill oil group (supplement group and 428 patients in the control group. Overall, it was found that fish and krill oils did not significantly alter warfarin time in therapeutic range (TTR or bleeding incidence, even when compared by gender. Conclusion: Omega-3 supplementation with fish and krill oil does not significantly affect long-term warfarin control and bleeding and thromboembolic events when consumed concurrently in patients managed at an anticoagulation clinic.

  9. Clinical decision-making for vitamin K-1 and K-2 deficiency and coronary artery calcification with warfarin therapy: are diet, factor Xa inhibitors or both the answer?

    Science.gov (United States)

    Wahlqvist, Mark L; Tanaka, Kiyoshi; Tzeng, Bing-Hsiean

    2013-01-01

    Coronary artery calcification is a recognised risk factor for ischaemic heart disease and mortality. Evidence is now strong that Mönckeberg's arteriosclerosis, a form of vascular calcification, can be attributable to vitamin K deficiency, but that vitamin K-2, especially the MK-4 form from foods like cheese can be protective. Warfarin blocks the recycling of hepatic and peripheral vitamin K leading to secondary vitamin K deficiency with adverse effects on vasculature, bone, kidneys, brain and other tissues and systems (inflammatory, immune function and neoplasia at least). There is individual susceptibility to vitamin K deficiency and warfarin sensitivity, partly explicable in terms of genetic polymorphisms, epigenetics, diet and pharmacotherapy. The emergence of extensive coronary calcification in a man with atrial fibrillation treated for a decade with warfarin is described by way of illustration and to raise the present clinical management conundrums. Finally, a putative set of recommendations is provided.

  10. [Optimization of technological processes for the preparation of tablets with a low content of warfarin by direct compression].

    Science.gov (United States)

    Muselík, Jan; Franc, Aleš; Starková, Jana; Matějková, Zuzana

    2014-10-01

    Warfarin is a rug with an arrow therapeutic index. It is commercially available in the form of tablets with immediate release from many generic manufacturers. Though attempts are being made to replace it with new drugs, in the U.S.A.it is still the antithrombotic agent of the first choice. In the past there were cases when after replacement of the original brand preparation with the generic one, the patient suffered from complications such as the loss of control of anticoagulation and increased frequency of patients visits to the physician. One of the critical parameters of tablets containing an active substance with an arrow therapeutic index (NTI) is content uniformity, which must comply with the pharmacopoeial requirements as well as the strict criteria of regulatory authorities in the validation of the manufacture of the solid dosage form. Content uniformity is affected by a number of factors such as density, particle shape and size distribution, electrostatic charge, and concentration of the individual components. Of the technological parameters, it is mainly the intensity and length of mixing, shape of the mixing vessel and the mixer, the size of the charge, or the degree of filling of the mixing device, etc. This paper deals with the influence of the mixing time and concentration of the drug on the content uniformity of warfarin-containing tablets. In mixing the mixtures of solid substances, where the active substance is included in alow concentration, there occurs the so-called mixing-out and segregation of the active substance. For this reason it is necessary to optimize the period of mixing. This study managed to optimize the mixing time of mixtures prepared with the use of the patented technology of the Veterinary and Pharmaceutical University Brno and further to prepare tablets with varying content of warfarin (2-10 mg) from acommon blend, which fulfil the pharmacopoeial requirements as well as the requirements of regulatory authorities for content

  11. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    Science.gov (United States)

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  12. Reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin.

    Directory of Open Access Journals (Sweden)

    Alessio Bocedi

    Full Text Available Human serum albumin (HSA, the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s. As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i of carbon monoxide (CO binding to ferrous human serum heme-albumin (HSA-heme-Fe(II by warfarin (WF, and (ii of WF binding to HSA-heme-Fe(II by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II, respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands. This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II. The HSA-heme-Fe(II populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i upon CO binding a conformational change of HSA-heme-Fe(II takes place (likely reflecting the displacement of an endogenous ligand by CO, and (ii CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II.

  13. Pharmacogenomics of warfarin and its personalized treatment%华法林药物基因组学和个体化用药

    Institute of Scientific and Technical Information of China (English)

    彭娟; 谭胜蓝; 周宏灏; 李智

    2013-01-01

    华法林是临床使用最广泛的口服抗凝药,其治疗窗窄,剂量个体差异大,容易发生出血或栓塞的风险.CYP2C9和VKORC1基因多态性明显影响华法林剂量.其他参与维生素摄入和循环,华法林转运的基因变异,以及microRNA也可能影响华法林剂量.该文结合国内外各种华法林稳定剂量预测模型研究,总结影响华法林剂量相关基因的最新研究进展,旨在为华法林个体化治疗提供参考和指导依据.%Warfarin is the most widely used oral anticoagulant with narrow therapeutic window, wide inter-individual variability and high risks of bleeding or thromboembolism. Polymorphisms in CYP2C9 and VKORC1 are the major determinants of warfarin dosage requirement. Other genetic factors involving in vitamin K intake and recycle, and warfarin transportation may influence warfarin stable maintenance dosage as well. microRNA might al-so play a role. Based on numerous warfarin stable dosage prediction algorithms studies, this review updates the studies of warfarin pharmacogenomics and its personalized treatment, with the aim of providing evidence for clinical practice.

  14. Bleeding Risk and Antithrombotic Strategy in Patients with Sinus Rhythm Heart Failure with Reduced Ejection Fraction Treated with Warfarin or Aspirin

    Science.gov (United States)

    Ye, Siqin; Cheng, Bin; Lip, Gregory Y. H.; Buchsbaum, Richard; Sacco, Ralph L.; Levin, Bruce; Di Tullio, Marco R.; Qian, Min; Mann, Douglas L.; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Mohr, J.P.; Graham, Susan; Labovitz, Arthur J.; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.; Thompson, John L.P.; Homma, Shunichi

    2015-01-01

    We sought to assess the performance of existing bleeding risk scores, such as HAS-BLED or OBRI, in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell’s c-statistic and net-reclassification improvement (NRI) index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly higher c-statistic (0.72 vs 0.61; p=0.03) compared to HAS-BLED, though the NRI for comparing OBRI to HAS-BLED was not significant (0.32, 95% CI - 0.18-0.37). Performance of the OBRI and HAS-BLED risk scores were similar for the aspirin arm. For participants with OBRI score of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (HR 0.51, 95% CI 0.26-0.98, p=0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66-2.30, p=0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27-1.15, p=0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99-8.22, p<0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in HFrEF patients in SR, and could be tested for potentially identifying patients with a favorable risk / benefit profile for antithrombotic therapy with warfarin. PMID:26189039

  15. Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis.

    Science.gov (United States)

    Nagata, Naoyoshi; Yasunaga, Hideo; Matsui, Hiroki; Fushimi, Kiyohide; Watanabe, Kazuhiro; Akiyama, Junichi; Uemura, Naomi; Niikura, Ryota

    2017-09-05

    To compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures. Using the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups. In the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk. The risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Management of Supratherapeutic International Normalized Ratio without Bleeding after Warfarin Use: An Evaluation of Vitamin K Administration (SUPRA-WAR-K Study).

    Science.gov (United States)

    Tai, Claire; Wu, Hilary; San, Cindy; Chua, Doson

    2017-01-01

    For patients with supratherapeutic international normalized ratio (INR) and no evidence of bleeding, the 2012 guidelines of the American College of Chest Physicians discourage administration of vitamin K. At the study hospital, it was observed that vitamin K was frequently prescribed for patients with INR of 4.5 or higher and no bleeding. To compare efficacy and safety outcomes between holding warfarin alone and holding warfarin with administration of vitamin K and to compare these outcomes among various doses and routes of vitamin K administration in non-critical care inpatients experiencing supratherapeutic INR without evidence of bleeding. This single-centre retrospective chart review involved noncritical care inpatients with supratherapeutic INR (4.5-8.9) without evidence of bleeding. The primary outcomes were the change in INR 1 day after implementation of supratherapeutic INR management and the time to reach INR less than 3.0. The secondary outcomes were length of stay, frequency of warfarin resistance, incidence and duration of bridging anticoagulation, incidence of thromboembolism and major bleeding, and death. Regardless of vitamin K dose, the administration of vitamin K combined with holding warfarin, relative to holding warfarin alone, was associated with a greater INR decrease 1 day after the intervention (mean ± standard deviation -3.2 ± 1.9 versus -0.9 ± 1.0, p K was associated with greater and faster decreases in INR than holding warfarin alone. No significant differences were found in clinically important outcomes. The practice of administering vitamin K in this population warrants further study and re-evaluation.

  17. Chemostimuli for guanylyl cyclase-D-expressing olfactory sensory neurons promote the acquisition of preferences for foods adulterated with the rodenticide warfarin

    Directory of Open Access Journals (Sweden)

    Kevin Robert Kelliher

    2015-07-01

    Full Text Available Many animals have the ability to acquire food preferences from conspecifics via social signals. For example, the coincident detection of a food odor by canonical olfactory sensory neurons (OSNs and agonists of the specialized OSNs expressing the receptor guanylyl cyclase GC-D (GC-D+ OSNs will promote a preference in recipient rodents for similarly odored foods. It has been hypothesized that these preferences are acquired and maintained regardless of the palatability or quality of the food. We assessed whether mice could acquire and maintain preferences for food that had been adulterated with the anticoagulant rodenticide warfarin. After olfactory investigation of a saline droplet containing either cocoa (2%, w/w or cinnamon (1%, w/w along with a GC-D+ OSN-specific chemostimulus (either of the guanylin-family peptides uroguanylin and guanylin; 1–50 nM, C57BL/6J mice exhibited robust preferences for unadulterated food containing the demonstrated odor. The peptide-dependent preference was observed even when the food contained warfarin (0.025% w/w. Repeated ingestion of warfarin-containing food over four days did not disrupt the preference, even though mice were not re-exposed to the peptide stimulus. Surprisingly, mice continued to prefer warfarin-adulterated food containing the demonstrated odor when presented with a choice of warfarin-free food containing a novel odor. Our results indicate that olfactory-mediated food preferences can be acquired and maintained for warfarin-containing foods and suggest that guanylin peptides may be effective stimuli for promoting the ingestion of foods or other edibles with low palatability or potential toxicity.

  18. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial.

    Science.gov (United States)

    Matsumoto, Masayasu; Hori, Masatsugu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-05-01

    The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

  19. Theoretical study of optical activity of 1:1 hydrogen bond complexes of water with S-warfarin

    Science.gov (United States)

    Dadsetani, Mehrdad; Abdolmaleki, Ahmad; Zabardasti, Abedin

    2016-11-01

    The molecular interaction between S-warfarin (SW) and a single water molecule was investigated using the B3LYP method at 6-311 ++G(d,p) basis set. The vibrational spectra of the optimized complexes have been investigated for stabilization checking. Quantum theories of atoms in molecules, natural bond orbitals, molecular electrostatic potentials and energy decomposition analysis methods have been applied to analyze the intermolecular interactions. The intermolecular charge transfer in the most stable complex is in the opposite direction from those in the other complexes. The optical spectra and the hyperpolarizabilities of SW-water hydrogen bond complexes have been computed.

  20. Beyond warfarin: the new generation of oral anticoagulants and their implications for the management of dental patients.

    Science.gov (United States)

    Firriolo, F John; Hupp, Wendy S

    2012-04-01

    Warfarin has been the primary anticoagulant drug used in the USA for more than 50 years. However, 2 novel types of oral anticoagulants have recently been approved for use in the USA. These are direct thrombin inhibitors (e.g., dabigatran etexilate) and factor Xa inhibitors (e.g., rivaroxaban). Dental health care providers may soon encounter patients who are being prescribed these medications. This article describes the pharmacologic properties and medical uses of these new oral anticoagulants. Also discussed are implications for the management of dental patients being treated with these new oral anticoagulants, including potential interactions with drugs commonly used or prescribed in the course of dental treatment.

  1. The effect of CYP2C9, VKORC1 and CYP4F2 polymorphism and of clinical factors on warfarin dosage during initiation and long-term treatment after heart valve surgery.

    Science.gov (United States)

    Tatarunas, Vacis; Lesauskaite, Vaiva; Veikutiene, Audrone; Grybauskas, Pranas; Jakuska, Povilas; Jankauskiene, Laima; Bartuseviciute, Ruta; Benetis, Rimantas

    2014-01-01

    The dosage of warfarin is restricted due to its narrow therapeutic index, so, the required dose must be adapted individually to each patient. Variations in warfarin dosage are influenced by genetic factors, the changes in patient diet, anthropometric and clinical parameters. To determine whether VKORC1 G3730A and CYP4F2 G1347A genotypes contribute to warfarin dosage in patients during initiation and long-term anticoagulation treatment after heart valve surgery. From totally 307 patients, who underwent heart valve surgery, 189 patients (62 %) who had been treated with warfarin more than 3 months, were included into the study. A hierarchical stepwise multivariate linear regression model showed, that during initiation clinical factors can explain 17 % of the warfarin dose variation. The addition of CYP2C9 and VKORC1 G-1639A genotype raises the accuracy about twice-to 32 %. The CYP4F2 G1347A genotype can add again about 2-34 %. During long-term treatment clinical factors explain about 26 % of warfarin dose variation. If the CYP2C9 *2, *3, VKORC1*2 alleles are detected, model can explain about 49 % in dose variation. The *3 allele of VKORC1 raises the accuracy by 1-50 %. The carriers of CYP4F2 A1347A genotype required higher daily warfarin doses during initiation of warfarin therapy after heart valve surgery than comparing to G/G and G/A carriers, but during the longer periods of warfarin use, the dosage of warfarin depended significantly on VKORC1 *3 allele (G3730A polymorphism) and on the thyroid stimulating hormone level in the blood plasma.

  2. Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population.

    Science.gov (United States)

    Krishna Kumar, Dhakchinamoorthi; Shewade, Deepak Gopal; Loriot, Marie-Anne; Beaune, Philippe; Balachander, Jayaraman; Sai Chandran, B V; Adithan, Chandrasekaran

    2014-01-01

    To determine the influence of genetic polymorphisms on warfarin maintenance dose and to explicate an algorithm using the pharmacogenetic and clinical factors to determine the maintenance and/or starting dose of warfarin in South Indian patients receiving warfarin therapy. Patients receiving stabilized warfarin therapy (n=257) were included in the study. Single nucleotide polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231, rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2 (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time-PCR method. The mean daily maintenance dose of warfarin was found to be 4.7 ± 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily maintenance dose of warfarin, respectively, than those patients with the CYP2C9*1/*1 wild-type genotype (5.2 mg) (pgenetic variants of CYP2C9, VKORC1 and GGCX were associated with decreased warfarin dose, except for rs7196161, rs7294 and rs2108622 which were associated with an increased warfarin dose. Genetic variations of CYP2C9 (*2 and *3), VKORC1 (rs9923231, rs7294, rs9934438 and rs2359612), CYP4F2, GGCX and non-genetic factors such as age, body weight, clinical status (post mechanical valve replacement) could explain up to 62.1 % of the overall variation (adjusted r (2) 60.2 %, pGenetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and GGCX are important predictive factors of warfarin maintenance dose, and the developed algorithm will be useful to predict the required maintenance and/or starting warfarin dose in South Indian populations.

  3. Design and rationale for the WARFA trial: a randomized controlled cross-over trial testing the therapeutic equivalence of branded and generic warfarin in atrial fibrillation patients in Brazil.

    Science.gov (United States)

    Freitas, Carolina Gomes; Walsh, Michael; Atallah, Álvaro Nagib

    2017-06-07

    Warfarin is a commonly used anticoagulant. Whether a given dose of the different formulations of Brazilian warfarin will result in the same effect on the international normalized ratio (INR) is uncertain. The aim of the WARFA trial is to determine whether the branded and two generic warfarins available in Brazil differ in their effect on the INR. WARFA is a cross-over RCT comparing three warfarins. The formulations tested are the branded Marevan® (Uniao Quimica/Farmoquimica) and two generic warfarin (manufactured respectively by Uniao Quimica Farmaceutica Nacional and Laboratorio Teuto Brasileiro). All of them were manufactured in Brazil, are available in all settings of the Brazilian healthcare system and were purchased from retail drugstores. Eligible participants had atrial fibrillation or flutter, had been using warfarin for at least 2 months with a therapeutic range of 2.0-3.0 and had low variability in INR results during the 1st period of the trial. Our primary outcome, for which we have an equality hypothesis, is the difference between warfarins in the mean absolute difference between two INR results, obtained after three and 4 weeks with each drug. Our secondary outcomes, that will be tested for inequality (except for the mean INR, which will be tested for equality), include the difference in the warfarin dose, and time in therapeutic range. Clinical events and adherence were also recorded and will be reported. To our knowledge, WARFA will be the first comparison of the more readily applicable INR results between branded and generic warfarins in Brazil. WARFA is important because warfarins are commonly switched between in the course of a chronic treatment in Brazil. Final results of WARFA are expected in May 2017. ClinicalTrials.gov NCT02017197 . Registered 11 December 2013.

  4. Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

    Science.gov (United States)

    Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

    2015-08-01

    The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

  5. PHARMACOECONOMIC EVALUATION OF DABIGATRAN VS WARFARIN IN CARDIOVASCULAR EVENTS PREVENTION IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

    Directory of Open Access Journals (Sweden)

    Yu. B. Belousov

    2015-12-01

    Full Text Available According to recent guidelines, oral dabigatran etexilate is indicated for stroke and systemic embolism prevention in patients with atrial fibrillation (AF. Aim. Based on the RE-LY study to evaluate the cost-effectiveness of dabigatran etexilate versus warfarin prescribed in “real-world” settings from a Russian payer perspective. Material and methods. Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were calculated using general tariff agreement of Russian obligatory health insurance system and official national statistics. Clinical events, summarized as events per 100 patient-years, expected life years, total costs, and incremental cost effectiveness ratios (ICER were calculated. Results. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages and fewer ischaemic strokes. ICER of dabigatran etexilate was 461,602 roubles per one additional life year versus “real-world” warfarin. Conclusion. This study demonstrates that dabigatran etexilate is a cost-effective alternative to current care for the prevention of stroke and systemic embolism among Russian patients with AF .

  6. PHARMACOECONOMIC EVALUATION OF DABIGATRAN VS WARFARIN IN CARDIOVASCULAR EVENTS PREVENTION IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

    Directory of Open Access Journals (Sweden)

    Yu. B. Belousov

    2012-01-01

    Full Text Available According to recent guidelines, oral dabigatran etexilate is indicated for stroke and systemic embolism prevention in patients with atrial fibrillation (AF. Aim. Based on the RE-LY study to evaluate the cost-effectiveness of dabigatran etexilate versus warfarin prescribed in “real-world” settings from a Russian payer perspective. Material and methods. Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events and resulting functional disability. Acute event costs and resulting long-term follow-up costs incurred by disabled stroke survivors were calculated using general tariff agreement of Russian obligatory health insurance system and official national statistics. Clinical events, summarized as events per 100 patient-years, expected life years, total costs, and incremental cost effectiveness ratios (ICER were calculated. Results. Over a lifetime, dabigatran etexilate treated patients experienced fewer intracranial haemorrhages and fewer ischaemic strokes. ICER of dabigatran etexilate was 461,602 roubles per one additional life year versus “real-world” warfarin. Conclusion. This study demonstrates that dabigatran etexilate is a cost-effective alternative to current care for the prevention of stroke and systemic embolism among Russian patients with AF .

  7. Laboratory assessment of warfarin reversal with global coagulation tests versus international normalized ratio in patients with intracranial bleeding.

    Science.gov (United States)

    Voils, Stacy A; Martin, Erika J; Mohammed, Bassem M; Bayrlee, Ahmad; Brophy, Donald F

    2015-06-01

    We assess the in-vivo relationship between international normalized ratio (INR) and global coagulation tests in patients with life-threatening bleeding who received prothrombin complex concentrate (PCC) for warfarin reversal. This was a prospective pilot study in adult patients with intracranial bleeding related to anticoagulation with warfarin. Thromboelastography (TEG), thrombin generation parameters and INR were assessed at baseline, 30  min, 2 and 24  h after PCC. Changes in laboratory parameters and relationship between INR and global coagulation tests were assessed over time. Eight patients mean [standard deviation (SD)] age 72 (16) were included and received mean (SD) dose of PCC 24 (5) units/kg. Four patients died during the study, all with INR values more than 1.5 thirty minutes after PCC. Mean (SD) INR was 3.0 (1.3) and decreased significantly to 1.8 (0.48) thirty minutes after PCC (P administration. Reaction (R)-time decreased significantly (P = 0.02), and maximum amplitude and overall coagulation index (CI) significantly increased during treatment (P administration; however, INR did not fully correct. Patients that died tended to be older with prolonged INR values across the study period. INR and TEG values correlated well with thrombin generation before administration of PCC, but this relationship was lost afterward.

  8. Anticoagulation therapy for thromboembolism prevention: a case of warfarin-induced skin necrosis in the setting of protein C deficiency.

    Science.gov (United States)

    Lai, Jonathan; Ramai, Daryl; Alchi, Ramiz; Bloomfield, Dennis

    2017-05-12

    Patients with protein C deficiency are at increased risk for thrombolic diseases. Non-vitamin K antagonist anticoagulant options should be considered in patients with warfarin-induced skin necrosis (WISN) in the setting of protein C. We report a 41-year-old African American male patient with WISN and protein C deficiency who was treated with rivaroxaban followed by dabigatran. After 1 month on rivaroxaban, he began experiencing blood in his stools, unrelenting pain in his lower extremities, found it difficult to obtain medication despite having insurance and as a result did not maintain compliance. He was then assessed at the hospital, symptomatically treated and discharged on dabigatran. After 6 weeks, he reported symptomatic relief and less side effects. This case involved a head-to-head clinical comparison of rivaroxaban and dabigatran as alternatives to warfarin anticoagulation therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Adverse Interaction between Capecitabine and Warfarin Resulting in Altered Coagulation Parameters: A Review of the Literature Starting from a Case Report

    Directory of Open Access Journals (Sweden)

    Giovanni Giunta

    2010-01-01

    Full Text Available Capecitabine is an orally active prodrug of fluorouracil and is extensively used as an antineoplastic agent. It is converted to 5-Fluorouracil in the liver and tumor tissues. Warfarin is an anticoagulant agent for preventing and treating venous and arterial thrombosis and embolism and is metabolized by cytochrome P450 isoenzymes in the liver. Preclinical in vitro studies using human liver microsomes report no inhibitory effects between capecitabine and substrates of cytochrome P. However, the concomitant administration of capecitabine and warfarin resulted in INR elevation in the cases previously reported in the literature. The exact mechanism of this interaction is unknown but may be related to downregulation of cytochrome P450 2C9 by capecitabine or its metabolites. We report on the possible adverse interaction between capecitabine and warfarin in a patient with metastatic breast cancer and critically review the existing literature on this topic. Physicians should be aware of adverse reactions arising from the combined use of capecitabine and warfarin. In the light of the current data, INR levels should be closely monitored in patients using these drugs together.

  10. 华法林基因导向的个体化抗凝研究进展%Research Progress in Warfarin Individualized Anticoagulation Based on Pharmacogenomics

    Institute of Scientific and Technical Information of China (English)

    沈为勤; 刘俊

    2015-01-01

    华法林是临床广泛使用的抗凝药,但其疗效存在明显个体差异,其中基因多态性是导致华法林剂量差异主要影响因素。本文查阅相关文献,综述与华法林剂量相关的基因,为临床华法林个体化应用提供参考。%Warfarin is one of the most frequently prescribed anticoagulant and there is significant indi-vidual variability in dose requirement for the clinical effect. Gene polymorphisms are the important factors that can influence the anticoagulant effect of warfain. Recently, warfarin gene polymorphisms become a re-search topic and a large number of individualized medication algorithms have been established. This article reviews warfarin dosage related gene polymorphisms in order to offer some suggestions for warfarin individ-ualized medication.

  11. Warfarin and coumarin-like Murraya paniculata extract down-regulate EpCAM-mediated cell adhesion: individual components versus mixture for studying botanical metastatic chemopreventives.

    Science.gov (United States)

    Shao, Jingwei; Zhou, Suxia; Jiang, Zhou; Chi, Ting; Ma, Ji; Kuo, Minliang; Lee, Alan Yueh-Luen; Jia, Lee

    2016-08-02

    We recently defined cancer metastatic chemoprevention as utilizing safe and effective molecules to comprehensively prevent the spark of activation-adhesion-extravasation-proliferation metastatic cascade caused by circulating tumor cells (CTCs). The strategy focuses on preventing the most important starting point of the cascade. We identified an extract from a well-known medical plant Murraya paniculata, which inhibited both embryonic implantation to human endometrium as traditionally-used for abortion and CTC adhesion to human endothelium. Here, we separated and characterized five coumarin-containing components (Z1-Z5) from the botanic extract. Flow cytometry revealed that within 1-100 μg/mL, Z3 and Z5 down-regulated EpCAM expression in human colon HCT116, whereas, Z1 and Z2 did oppositely. Warfarin and Z1-Z5 component mixture (CM) also down-regulated EpCAM expression. The down-regulation of EpCAM by Z3, Z5, CM and warfarin was confirmed by western blotting, and caused inhibition on adhesion of cancer cells to human endothelial cells. Rat coagulation study showed that warfarin prolonged prothrombin time, whereas, Z3 did not. The present studies revealed that, for the first time, warfarin and coumarin-like components Z3, Z5 and CM from Murraya paniculata could directly inhibit EpCAM-mediated cell-cell adhesion.

  12. COST-EFFECTIVENESS OF APIXABAN AS COMPARED WITH WARFARIN AND ACETYLSALICYLIC ACID IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2015-09-01

    Full Text Available Background. For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (such as warfarin, antiplatelet therapy (such as acetylsalicylic acid and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Administration of vitamin K antagonists (VKA is complicated by the need for individual dose adjustment and frequent monitoring of international normalized ratio (INR. Both warfarin and acetylsalicylic acid are widely used for thrombosis prevention in patients with NVAF in the Russian Federation.Aim. To evaluate the cost-effectiveness ratio of apixaban compared with warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective.Material and methods. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER for apixaban as compared with warfarin and acetylsalicylic acid over lifetime horizon in VKA suitable and VKA unsuitable patients with NVAF respectively. The model enclosed cardiovascular event rates based on the results of the randomized clinical trials comparing clinical effectiveness and safety of apixaban with warfarin (ARISTOTLE and acetylsalicylic acid (AVERROES. The following cardiovascular events were taken into consideration: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the antithrombotic drugs was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality

  13. COST-EFFECTIVENESS OF APIXABAN AS COMPARED WITH WARFARIN AND ACETYLSALICYLIC ACID IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2014-01-01

    Full Text Available Background. For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (such as warfarin, antiplatelet therapy (such as acetylsalicylic acid and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Administration of vitamin K antagonists (VKA is complicated by the need for individual dose adjustment and frequent monitoring of international normalized ratio (INR. Both warfarin and acetylsalicylic acid are widely used for thrombosis prevention in patients with NVAF in the Russian Federation.Aim. To evaluate the cost-effectiveness ratio of apixaban compared with warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective.Material and methods. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER for apixaban as compared with warfarin and acetylsalicylic acid over lifetime horizon in VKA suitable and VKA unsuitable patients with NVAF respectively. The model enclosed cardiovascular event rates based on the results of the randomized clinical trials comparing clinical effectiveness and safety of apixaban with warfarin (ARISTOTLE and acetylsalicylic acid (AVERROES. The following cardiovascular events were taken into consideration: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the antithrombotic drugs was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality

  14. Clinical presentation and course of bleeding events in patients with venous thromboembolism, treated with apixaban or enoxaparin and warfarin. Results from the AMPLIFY trial.

    Science.gov (United States)

    Bleker, Suzanne M; Cohen, Alexander T; Büller, Harry R; Agnelli, Giancarlo; Gallus, Alexander S; Raskob, Gary E; Weitz, Jeffrey I; Curto, Madelyn; Sisson, Melanie; Middeldorp, Saskia

    2016-11-30

    Apixaban, a direct acting oral anticoagulant (DOAC), was found to be non-inferior to and safer as enoxaparin followed by warfarin for treatment of venous thromboembolism (VTE) in the AMPLIFY trial. Information is needed on how bleeding events with DOACs present and develop. In this post-hoc analysis, the clinical presentation and course of all major and clinically relevant non major (CRNM) bleeding events in the AMPLIFY trial were blindly classified by three investigators, using pre-designed classification schemes containing four categories. Odds ratios (OR) for classifying as category three or four (representing a more severe clinical presentation and course) were calculated between apixaban and enoxaparin/warfarin. In total, 63 major and 311 CRNM bleeding events were classified. Of the major bleeds, a more severe clinical presentation occurred in 28.5 % of apixaban versus 44.9 % of enoxaparin/warfarin related recipients (OR 0.49, 95 % confidence interval [CI] 0.14-1.78). A severe clinical course was observed in 14.3 % and in 12.2 %, respectively (OR 1.19, 95 %CI 0.21-6.69). Of the CRNM bleeding events, a more severe clinical presentation and extent of clinical care was found in 25 % of apixaban recipients compared to 22.7 % in the enoxaparin/warfarin group (OR 1.13, 95 %CI 0.65-1.97). The clinical presentation and course of major and CRNM bleeds were similar in apixaban and enoxaparin/warfarin treated patients. This finding should reassure physicians and patients that even in the absence of a specific reversal agent, apixaban is a convenient and safe choice for VTE.

  15. Impact of a pharmacist-led warfarin self-management program on quality of life and anticoagulation control: a randomized trial.

    Science.gov (United States)

    Verret, Lucie; Couturier, Justine; Rozon, Andréanne; Saudrais-Janecek, Sarah; St-Onge, Amélie; Nguyen, Angela; Basmadjian, Arsène; Tremblay, Simon; Brouillette, Denis; de Denus, Simon

    2012-10-01

    To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic. Prospective, randomized, controlled, open-label trial. Tertiary care academic medical center. A total of 114 patients aged 18-75 years who were followed at a specialized anticoagulation clinic, had received warfarin for at least 6 months, and were expected to continue warfarin for a minimum of 4 months. All patients attended an educational session on anticoagulation provided by a pharmacist. Patients randomized to the self-management group (58 patients) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm. Patients in the control group (56 patients) continued to undergo standard management at the anticoagulation clinic. Patients completed a validated quality-of-life questionnaire and the validated Oral Anticoagulation Knowledge test at the beginning and end of the study. The quality of anticoagulation control was evaluated by using the time spent in therapeutic range. After 4 months of follow-up, a significant improvement in the self-management group was observed compared with the control group in four of the five quality-of-life topics (pself-management group vs 75% in the control group, p=0.79) and in the extended therapeutic range ([target international normalized ratio ± 0.3] 93.2% in the self-management group vs 91.1% in the control group, p=0.30) were similar between groups. A self-management warfarin program led by pharmacists resulted in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring, while maintaining a level of anticoagulation control similar to a high-quality specialized anticoagulation clinic. © 2012 Pharmacotherapy Publications, Inc.

  16. The development and feasibility of a remote damage control resuscitation prehospital plasma transfusion protocol for warfarin reversal for patients with traumatic brain injury.

    Science.gov (United States)

    Zielinski, Martin D; Smoot, Dustin L; Stubbs, James R; Jenkins, Donald H; Park, Myung S; Zietlow, Scott P

    2013-01-01

    The rapid reversal of warfarin in the setting of traumatic brain injury (TBI) has been associated with improved outcomes. Until now, remote reversal of hypocoagulable states has not been possible in the prehospital environment. This manuscript describes the development and analysis of a prehospital plasma transfusion protocol to reverse warfarin at the earliest possible moment after TBI. A retrospective review of all TBI patients receiving plasma transfusion(s) in the prehospital environment for warfarin reversal between February 2009 and September 2010 was conducted. Thawed plasma was carried on every air ambulance flight centered at the main campus. A total of 2836 flights carried over 2500 units of thawed plasma throughout the study period. During this time, 16 patients received prehospital plasma resuscitation, five of who were on warfarin with a concurrent TBI. The median Injury Severity Score was 17 (8.5-27.5) with a median Glasgow Coma Score of 13 (8-15) and a mortality rate of 40%. A median of 2 (1.5-2.0) units of thawed plasma and 0 (0-0) units of RBCs were transfused en route. The pretransfusion point-of-care international normalized ratio improved from 3.1 (2.3-4.0) to 1.9 (1.3-3.6) upon trauma center admission (serum sample). One hundred percent of the transported, but unused, thawed plasma underwent subsequent transfusion prior to expiration. Remote prehospital plasma transfusions effectively reverse anticoagulation secondary to warfarin administration in TBI patients. It is feasible to transfuse thawed plasma in the prehospital setting via remote damage control techniques without increasing waste. Prospective studies are needed to determine if this practice can improve outcomes in this population. © 2013 American Association of Blood Banks.

  17. Comparison of the Risk of Gastrointestinal Bleeding among Different Statin Exposures with Concomitant Administration of Warfarin: Electronic Health Record-Based Retrospective Cohort Study.

    Science.gov (United States)

    Shin, Dahye; Yoon, Dukyong; Lim, Sun Gyo; Hong, Ji Man; Park, Rae Woong; Lee, Jin Soo

    2016-01-01

    Patients who should be treated with both warfarin and a statin are frequently seen in vascular clinics. The risk for bleeding and potential drug interactions should be considered when prescribing both medications together. This study aimed to compare the risk for gastrointestinal bleeding among different statin exposures with concomitant administration of warfarin. This is a single-hospital retrospective cohort study. We included patients who were concomitantly exposed to one of four statins (pravastatin, simvastatin, atorvastatin, and rosuvastatin) and warfarin for up to 2 years (730 days). The observation period ended when a gastrointestinal bleeding event occurred or the observation was censored. Within-class comparisons were used, and 1:1 matching using a propensity score was performed for comparisons between each statin and all of the other statins. Kaplan-Meier analyses with log-rank tests and Cox proportional hazard regression analyses were conducted to determine associations with the risk of gastrointestinal bleeding. Data were analyzed for 1,686 patients who were concomitantly administered a statin and warfarin. Log-rank tests for the gastrointestinal bleeding-free survival rate showed that the risk for gastrointestinal bleeding was significantly lower in the pravastatin group (p = 0.0499) and higher in the rosuvastatin group (p = 0.009). In the Cox proportional hazard regression analysis, the hazard ratio of 5.394 for gastrointestinal bleeding based on statin exposure in the rosuvastatin group was significant (95% confidence interval, 1.168-24.916). There was a relatively high risk of gastrointestinal bleeding with rosuvastatin when administered concomitantly with warfarin.

  18. Potentially avoidable inpatient nights among warfarin receiving patients; an audit of a single university teaching hospital.

    LENUS (Irish Health Repository)

    Forde, Dónall

    2009-01-01

    BACKGROUND: Warfarin is an oral anticoagulant (OAT) that needs active management to ensure therapeutic range. Initial management is often carried out as an inpatient, though not requiring inpatient facilities. This mismatch results in financial costs which could be directed more efficaciously. The extent of this has previously been unknown. Here we aim to calculate the potential number of bed nights which may be saved among those being dose optimized as inpatients and examine associated factors. METHODS: A 6 week prospective audit of inpatients receiving OAT, at Cork University Hospital, was carried out. The study period was from 11th June 2007 to 20th July 2007. Data was collected from patient\\'s medications prescription charts, medical record files, and computerised haematology laboratory records. The indications for OAT, the patient laboratory coagulation results and therapeutic intervals along with patient demographics were analysed. The level of potentially avoidable inpatient nights in those receiving OAT in hospital was calculated and the potential cost savings quantified. Potential avoidable bed nights were defined as patients remaining in hospital for the purpose of optimizing OAT dosage, while receiving subtherapeutic or therapeutic OAT (being titred up to therapeutic levels) and co-administered covering low molecular weight heparin, and requiring no other active care. The average cost of euro638 was taken as the per night hospital stay cost for a non-Intensive Care bed. Ethical approval was granted from the Ethical Committee of the Cork Teaching Hospitals, Cork, Ireland. RESULTS: A total of 158 patients were included in the audit. There was 94 men (59.4%) and 64 women (40.6%). The mean age was 67.8 years, with a median age of 70 years.Atrial Fibrillation (43%, n = 70), followed by aortic valve replacement (15%, n = 23) and pulmonary emboli (11%, n = 18) were the commonest reasons for prescribing OAT. 54% had previously been prescribed OAT prior to

  19. An assessment of the management of patients on warfarin by general dental practitioners in South West Wales.

    Science.gov (United States)

    Muthukrishnan, A; Bishop, K

    2003-11-22

    For anticoagulation therapy, warfarin is used to reduce the risk of thrombo-embolic events in patients with mechanical prosthetic heart valves, certain cardiovascular conditions, deep vein thrombosis (DVT) and hypercoagulable states.(1). The International Normalised Ratio (INR) is used as a measure of anticoagulation and is expressed as a ratio of the patient's prothrombin time (PT) to control prothrombin time. In a person with a normal PT, the INR is approximately 1. The therapeutic range is the value of INR or degree of anticoagulation required to prevent the development of serious thrombo-embolism and is normally maintained between 2.0 and 4.5. It is important to recognize that the INR is only valid for patients on well controlled anticoagulant therapy, ie where the level of anticoagulation is reasonably stable over a moderate length of time.(2).

  20. Comparison of the Performance of the Warfarin Pharmacogenetics Algorithms in Patients with Surgery of Heart Valve Replacement and Heart Valvuloplasty.

    Science.gov (United States)

    Xu, Hang; Su, Shi; Tang, Wuji; Wei, Meng; Wang, Tao; Wang, Dongjin; Ge, Weihong

    2015-09-01

    A large number of warfarin pharmacogenetics algorithms have been published. Our research was aimed to evaluate the performance of the selected pharmacogenetic algorithms in patients with surgery of heart valve replacement and heart valvuloplasty during the phase of initial and stable anticoagulation treatment. 10 pharmacogenetic algorithms were selected by searching PubMed. We compared the performance of the selected algorithms in a cohort of 193 patients during the phase of initial and stable anticoagulation therapy. Predicted dose was compared to therapeutic dose by using a predicted dose percentage that falls within 20% threshold of the actual dose (percentage within 20%) and mean absolute error (MAE). The average warfarin dose for patients was 3.05±1.23mg/day for initial treatment and 3.45±1.18mg/day for stable treatment. The percentages of the predicted dose within 20% of the therapeutic dose were 44.0±8.8% and 44.6±9.7% for the initial and stable phases, respectively. The MAEs of the selected algorithms were 0.85±0.18mg/day and 0.93±0.19mg/day, respectively. All algorithms had better performance in the ideal group than in the low dose and high dose groups. The only exception is the Wadelius et al. algorithm, which had better performance in the high dose group. The algorithms had similar performance except for the Wadelius et al. and Miao et al. algorithms, which had poor accuracy in our study cohort. The Gage et al. algorithm had better performance in both phases of initial and stable treatment. Algorithms had relatively higher accuracy in the >50years group of patients on the stable phase. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Treatment of natto, a fermented soybean preparation, to prevent excessive plasma vitamin K concentrations in patients taking warfarin.

    Science.gov (United States)

    Homma, Kazuhiro; Wakana, Noriaki; Suzuki, Yoshimi; Nukui, Mai; Daimatsu, Takaki; Tanaka, Etsuro; Tanaka, Kazuo; Koga, Yasuhiro; Nakajima, Yukiko; Nakazawa, Hiroe

    2006-10-01

    The purpose of this study is to find a method of cooking natto that prevents the appearance of high-plasma vitamin K concentrations after the consumption of natto, so that patients taking warfarin can benefit from eating natto. Five cooking methods were examined to determine which could most effectively decrease the count of the living Bacillus subtilis in natto. Volunteers ate natto or treated natto, and their plasma vitamin K level was measured at 5, 8, 24 and 48 h thereafter. One gram of natto contained 9.7+/-0.1 Log cfu/mL of Bacillus subtilis. Boiling significantly reduced the Bacillus subtilis count to 5.1+/-0.3 Log cfu/mL, and concomitantly reduced the content of menaquinone-7 (MK-7), which is a form of vitamin K synthesized by Bacillus subtilis, from 660.40+/-65.32 ng/mL to 78.50+/- 11.12 ng/mL. Untreated natto increased the MK-7 concentration in blood from 1.86+/-1.51 ng/mL to 14.54+/-4.12 ng/mL at 5 h after intake, and the MK-7 concentration remained elevated at 8, 24 and 48 h (7.29+/-2.20, 6.97+/-2.60, and 5.37+/-1.94 ng/mL, respectively). In contrast, boiled natto increased plasma MK-7 only mildly (from 1.61+/-1.11 to 4.02+/-0.82 ng/ mL at 5 h) and the concentration remained relatively stable up to 48 h (3.46+/-0.83, 4.22+/-1.51 and 2.77+/-0.75 ng/mL at 8, 24 and 48 h, respectively). In conclusion, boiled natto did not cause a marked increase in the plasma concentration of vitamin K in subjects who consumed it. Thus, patients on warfarin may be able to eat boiled natto without ill effects.

  2. Development and validation of X-ray diffraction method for quantitative determination of crystallinity in warfarin sodium products.

    Science.gov (United States)

    Siddiqui, Akhtar; Rahman, Ziyaur; Korang-Yeboah, Maxwell; Khan, Mansoor A

    2015-09-30

    The objective of this study was to develop and validate XRPD analytical method for the estimation of percent crystalline warfarin sodium present in drug products. Warfarin sodium (WS) is a clathrate containing Isopropyl alcohol entrapped in the crystalline structure. Four types of WS-excipient mixtures were prepared and used to make four formulations: M1 containing lactose monohydrate (WS: excipient 1:9), M2 containing anhydrous lactose (WS: excipient 1:9), M3 containing lactose monohydrate (WS: excipient 1:21.5), M4 containing lactose anhydrous (WS: excipient 1:21.5). Thoroughly mixed powders were packed in the XRD sample holders and diffractogram were collected. Diffractogram in the 7-9 2θ were found to be distinctive as the peak intensity grows with increasing percent crystalline WS. This peak region was, therefore, used to validate the XRPD method. Validation parameters were evaluated for accuracy, precision, linearity, limit of detection (LOD), and limit of quantitation (LOQ). LOD and LOQ for M1, M2, M3, and M4 were 3.04, 3.17, 4.17, 4.49% and 9.21, 9.62, 12.65, 13.30%, respectively. The method was found to be linear with R(2)>0.99. With changing scan speed, X-ray power output, and type of sample holder, the method was found to be robust. Prediction of the % crystalline content of the WS sample with known crystallinity showed close agreement between actual and predicted value. In summary, XRPD method was validated, which can be used as a quantitative method for the estimation of % crystalline WS present in a drug product.

  3. A chiral HPLC-MS/MS method for simultaneous quantification of warfarin enantiomers and its major hydroxylation metabolites of CYP2C9 and CYP3A4 in human plasma

    OpenAIRE

    2014-01-01

    Warfarin is an oral anticoagulant that requires frequent therapeutic drug monitoring due to a narrow therapeutic window, considerable interindividual variability in drug response, and susceptibility to drug-drug and drug-diet interactions. Enantiomeric separation and quantification of warfarin enantiomers and clinically important major hydroxylation metabolites are essential for drug interaction studies and phenotypic characterization of CYP2C9 and CYP3A4, the major cytochrome P450 (CYP) enzy...

  4. Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin.

    Science.gov (United States)

    Ye, Siqin; Cheng, Bin; Lip, Gregory Y H; Buchsbaum, Richard; Sacco, Ralph L; Levin, Bruce; Di Tullio, Marco R; Qian, Min; Mann, Douglas L; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Mohr, J P; Graham, Susan; Labovitz, Arthur J; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

    2015-09-15

    We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin.

  5. A team-based approach to warfarin management in long term care: A feasibility study of the MEDeINR electronic decision support system

    Directory of Open Access Journals (Sweden)

    Wang Luqi

    2010-06-01

    Full Text Available Abstract Background Previous studies in long-term care (LTC have demonstrated that warfarin management is suboptimal with preventable adverse events often occurring as a result of poor International Normalized Ratio (INR control. To assist LTC teams with the challenge of maintaining residents on warfarin in the therapeutic range (INR of 2.0 to 3.0, we developed an electronic decision support system that was based on a validated algorithm for warfarin dosing. We evaluated the MEDeINR system in a pre-post implementation design by examining the impact on INR control, testing frequency, and experiences of staff in using the system. Methods For this feasibility study, we piloted the MEDeINR system in six LTC homes in Ontario, Canada. All128 residents (without a prosthetic valve who were taking warfarin were included. Three-months of INR data prior to MEDeINR was collected via a retrospective chart audit, and three-months of INR data after implementation of MEDeINR was captured in the central computer database. The primary outcomes compared in a pre-post design were time in therapeutic range (TTR and time in sub/supratherapeutic ranges based on all INR measures for every resident on warfarin. Secondary measures included the number of monthly INR tests/resident and survey/focus-group feedback from the LTC teams. Results LTC homes in our study had TTR's that were higher than past reports prior to the intervention. Overall, the TTR increased during the MEDeINR phase (65 to 69%, but was only significantly increased for one home (62% to 71%, p Conclusion Although LTC homes in our sample had TTR's that were relatively high prior to the intervention, the MEDeINR program represented a useful tool to promote optimal TTR, decrease INR venipunctures, streamline processes, and increase nurse and physician confidence around warfarin management. We have demonstrated that MEDeINR was a practical, usable clinical information system that can be incorporated into the

  6. Prediction of rates of thromboembolic and major bleeding outcomes with dabigatran or warfarin among patients with atrial fibrillation: new initiator cohort study

    Science.gov (United States)

    Franklin, Jessica M; Glynn, Robert J; Schneeweiss, Sebastian; Eddings, Wesley; Gagne, Joshua J

    2016-01-01

    Objectives To compare stratified event rates from randomized controlled trials with predicted event rates from models developed in observational data, and assess their ability to accurately capture observed rates of thromboembolism and major bleeding for patients treated with dabigatran or warfarin as part of routine care. Design New initiator cohort study. Setting Data from United Health (October 2009 to June 2013), a commercial healthcare claims database in the United States. Participants 21 934 adults with atrial fibrillation initiating dabigatran (150 mg dose only) or warfarin treatment as part of routine care. Main outcome measures Predicted annual rates of thromboembolism or major bleeding, based on estimates from randomized controlled trials, models developed in routine care patients, and baseline risk scores (CHADS2, CHA2DS2-VASc, and HAS-BLED). Thromboembolism was a composite outcome, including primary inpatient diagnosis codes for ischemic or ill defined stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, and systemic embolism. Major bleeding was a composite outcome including codes occurring in an inpatient setting for hemorrhagic stroke; major upper, lower, or unspecified gastrointestinal bleed; and major urogenital or other bleed. Results 6516 (30%) and 15 418 (70%) of patients initiated dabigatran and warfarin, respectively. Annual event rates per 100 patients were 1.7 for thromboembolism and 4.6 for major bleeding. For thromboembolism, calibration of estimates from randomized controlled trials was similar to calibration for model based predictions; however, trial estimates for major bleeding consistently underestimated the rate of bleeding among patients in routine care. Underestimation of bleeding rates was particularly pronounced in warfarin initiators with high HAS-BLED scores, where event rates were underestimated by up to 4.0 per 100 patient years. Harrell’s c indices for discrimination for thromboembolism or

  7. A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case–control study

    Directory of Open Access Journals (Sweden)

    Azoulay Laurent

    2012-06-01

    Full Text Available Abstract Background As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF. Methods A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993–2008 was conducted within the United Kingdom General Practice Research Database. A nested case–control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year was calculated by subtracting the ischemic stroke rate (prevented by therapy from the intracranial hemorrhage (ICH rate (increased by therapy. Results The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73. However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54 and above (−0.49, 95% CI: -1.13, 0.15 therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (−0.07, 95% CI: -0.22, 0.08, though it was seen in certain subgroups. Conclusions Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.

  8. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

    DEFF Research Database (Denmark)

    Halperin, Jonathan L; Hankey, Graeme J; Wojdyla, Daniel M;

    2014-01-01

    BACKGROUND: Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compar...... younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly....

  9. Risk of major bleeding at different PT-INR ranges in elderly Japanese patients with non-valvular atrial fibrillation receiving warfarin: a nested case-control study

    OpenAIRE

    Ohgushi, Atsushi; Ohtani, Takayuki; Nakayama, Natsumi; Asai, Shigeo; Ishii, Yoshiyuki; Namiki, Atsuo; Akazawa, Manabu; Echizen, Hirotoshi

    2016-01-01

    Background Debate continues about the optimal anticoagulation level for elderly Japanese patients with non-valvular atrial fibrillation (NVAF) receiving warfarin. The Japanese Circulation Society guideline has recommended prothrombin time-international normalized ratios (PT-INR) of 1.6 – 2.6 for elderly patients and 2.0 – 3.0 for non-elderly patients, because previous observational studies indicated increased risk of bleeding when the ratio exceeded 2.6. We aimed to reappraise the relationshi...

  10. Assessment and evaluation efficacy of a clinical pharmacist-led inpatient warfarin knowledge education program and follow-up at a Chinese tertiary referral teaching hospital

    Directory of Open Access Journals (Sweden)

    Guy-Armel Bounda

    2013-01-01

    Conclusion: Chinese patients on warfarin therapy should benefit from periodic educational efforts reinforcing key medication safety information. Patient education is not a once-off procedure. A complete patient education program run by a clinical pharmacist in a Cardio-thoracic ward can considerably improve and enhance to reduce the hospital stays and significantly enlighten the role of the patient education in adherence to therapy.

  11. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    Science.gov (United States)

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR 3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  12. The Effect of Medicinal Education on Adherence Taking Warfarin in Acute Coronary Syndrome (ACS and Atrial Fibrilation (AF Patients at PKU Muhammadiyah Yogyakarta Hospital

    Directory of Open Access Journals (Sweden)

    Jastria Pusmarani

    2015-12-01

    Full Text Available In order to improve warfarin medication adherence in patient with Acute Coronary Syndrome (ACS and Atrial Fibrillation (AF, giving education with leaflet administration is one of the solutions. This study was aim to know the impact of pharmacist education with using prepared leaflet on the adherence to warfarin in ACS and AF patients. This study used pre test and post test with control group design. Data were collected prospectively during 8 weeks in June–July 2014 at the ambulatory ACS and AF patients at PKU Muhammadiyah Yogyakarta hospital, Indonesia. Data were collected by medical record and the questionnaire using Morisky Medication Adherence Scale (MMAS. Wilcoxon test was used for statistical analysis. The results shows pre test and post test value in the control group was p=0.194 and pre and post test value in the test group was p=0.058. There was no significant difference (p>0.05 after giving education with leaflet. The education with leaflet had no effect to adherence in warfarin in ACS and AF patients at PKU Muhammadiyah Yogyakarta hospital.

  13. Bilateral rectus sheath haematoma complicating dengue virus infection in a patient on warfarin for mechanical aortic valve replacement: a case report.

    Science.gov (United States)

    Rosa, Chamith Thushanga; Navinan, Mitrakrishnan Rayno; Samarawickrama, Sincy; Hamza, Himam; Gunarathne, Maheshika; Arulanantham, Arulprashanth; Subba, Neeha; Samarasiri, Udari; Mathias, Thushara; Kulatunga, Aruna

    2017-01-07

    The management of Dengue virus infection can be challenging. Varied presentations and numerous complications intrinsic to dengue by itself increase the complexity of treatment and potential mortality. When burdened with the presence of additional comorbidities and the need to continue compulsory medications, clear stepwise definitive guidance is lacking and patients tend to have more complex complications and outcomes calling to question the clinical decisions that may have been taken. The use and continuation of warfarin in dengue virus infection is one such example. We report a 65 year old South Asian female who presented with dengue fever. She had a history bronchial asthma, a prior abdominal surgery, and was on warfarin and maintained a therapeutically appropriate internationalized normalized ratio for a mechanical aortic valve replacement. Though preemptive decision to stop warfarin was taken with decreasing platelet counts, her clinical course was complicated with the development of bilateral rectus sheath haematoma's requiring resuscitation with blood transfusions. Though management of dengue viral fever has seen drastic evolution with recent updated guidance, clinical scenarios seen in the course of the illness still pose challenges to the managing physician. The need to continue obligatory anticoagulation which may seem counterintuitive during a complex disease such as dengue virus infection must be considered after understanding the potential risks versus that of its benefits. Though case by case decisions maybe warranted, a clear protocol would be very helpful in making clinical decisions, as the correct preemptive decision may potentially avert catastrophic and unpredictable bleeding events.

  14. An electrochemical sensor for warfarin determination based on covalent immobilization of quantum dots onto carboxylated multiwalled carbon nanotubes and chitosan composite film modified electrode.

    Science.gov (United States)

    Gholivand, Mohammad Bagher; Mohammadi-Behzad, Leila

    2015-12-01

    A method is described for the construction of a novel electrochemical warfarin sensor based on covalent immobilization of CdS-quantum dots (CdS-QDs) onto carboxylated multiwalled carbon nanotubes/chitosan (CS) composite film on the surface of a glassy carbon electrode. The CdS-QDs/CS/MWCNTs were characterized by field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infra-red (FTIR) spectroscopy, XRD analysis and electrochemical impedance spectroscopy (EIS). The sensor showed optimum anodic stripping response within 90s at an accumulation potential of 0.75V. The modified electrode was used to detect the concentration of warfarin with a wide linear range of 0.05-80 μM and a detection limit (S/N=3) of 8.5 nM. The proposed sensor has good storage stability, repeatability and reproducibility and was successfully applied for the determination of warfarin in real samples such as urine, serum and milk. Copyright © 2015. Published by Elsevier B.V.

  15. The value of education and self-monitoring in the management of warfarin therapy in older patients with unstable control of anticoagulation.

    Science.gov (United States)

    Khan, Tayyaba Irfan; Kamali, Farhad; Kesteven, Patrick; Avery, Peter; Wynne, Hilary

    2004-08-01

    Of 125 patients aged 65 years or over, with atrial fibrillation taking warfarin for at least 12 months, with a standard deviation (SD) of prothrombin time, expressed as the International Normalized Ratio (INR) >0.5 over the previous 6 months, 40 were randomized to continue with usual clinic care and 85 to receive education about warfarin. Of these, 44 were randomized to self-monitor their INR and 41 returned to clinic. Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [61.1 vs. 70.4; mean difference 8.8; 95% confidence interval (CI): -0.2-17.8; P = 0.054] and following education and self-monitoring (57 vs. 71.1; mean difference 14.1; 95% CI: 6.7-21.5; P control group. Inter-group differences were not statistically significant (intervention groups 0.26 +/- 0.30 vs. control 0.16 +/- 0.3, P = 0.10). Quality-of-life measurements and health beliefs about warfarin were unchanged (apart from emotional role limitation) with education or education and self-monitoring. Patient education regarding anticoagulation therapy could be a cost-effective initiative and is worthy of further study.

  16. Warfarin individualize therapy based on genotype%基因导向华法林个体化治疗

    Institute of Scientific and Technical Information of China (English)

    程智; 朱雪萍; 赵宁民; 李巧艳; 马永成; 马爱玲; 段虹飞

    2015-01-01

    There is tremendous interindividual variability in the response to pharmacologic agents.Plasma drug levels can vary more than 10-fold when the same drug dose is administered to two individuals having approximately the same weight.Drug-drug interactions,drug-food interactions,sex,age,disease state (ie,renal and hepatic function) and pregnancy can all influence variability in drug responses between patients.Genetic factors are also likely to play a major role,since the individual response to a given pharmacologic agent is highly reproducible.Pharmacogenomics is the study of the role of inherited and acquired genetic variation on drug response.The identification of genetic factors that influence drug absorption,metabolism,and action at the receptor level should allow for individualized therapy.This could optimize drug efficacy and minimize toxicity profiles.This article will take warfarin as an example,to review the research status of warfarin pharmacogenomics,and to provide the basis for clinical rational use of drugs.%人体对药物的反应存在巨大的个体差异,体重相近的两个人给予相同剂量的药物,他们各自的血浆药物浓度水平可能相差10倍以上.药物相互作用、药物与食物相互作用、性别、年龄、疾病状态(即肾脏和肝脏的功能)以及妊娠都可能引发药物反应的个体差异.遗传因素也可能起到了重要作用,因为每个个体对药物的反应具有高度可再现性.药物基因组学是研究遗传性及获得性基因变异对药物反应作用的一门学科.证实影响药物吸收、代谢以及作用(在受体水平时)的遗传机制,使个体化治疗成为可能,使药物疗效最优化,药物的毒性最小化.本研究将以华法林为例,综述华法林药物基因组学的研究现状,为临床合理用药提供依据.

  17. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

    Science.gov (United States)

    Cohen, H; Doré, C J; Clawson, S; Hunt, B J; Isenberg, D; Khamashta, M; Muirhead, N

    2015-09-01

    The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5. © The Author(s) 2015.

  18. Influence of Diet Vitamin K Intake on Warfarin Anticoagulation Therapy%饮食摄入维生素K对华法林抗凝治疗的影响

    Institute of Scientific and Technical Information of China (English)

    潘登

    2012-01-01

    Influence of Diet Vitamin K Intake on Warfarin Anticoagulation Therapy PAN Deng,ZHAI Ming. ( Warfarin as an oral vitamin K antagonist is widely used for anticoagulation. It is discovered in re-rent years that the diet vitamin K intake can greatly influence the warfarin response. High diet vitamin K intake causes insensibility of warfarin treatment and low diet vitamin K intake causes instability of warfarin treatment. Supplement of vitamin K or other diet intervention may increase the stability of warfarin treatment. The adjust-ment of vitamin K intake may become an alternative 01 warfarin to change piothiombin time-international normal ized ratio.%维生素K拮抗剂华法林广泛应用于临床的抗凝治疗,近年来研究发现,饮食中维生素K的摄入对华法林治疗的反应有很大影响.高维生素K摄入与华法林初始治疗敏感性差相关,低维生素K摄入与华法林治疗的稳定性差相关.补充维生素K或其他饮食干预措施可能有助于提高华法林抗凝治疗的稳定性.调整饮食维生素K的摄入量替代调整华法林剂量有可能成为调整凝血酶原时间-国际标准化比值的另一种方法.

  19. Effect of Complexation with Arabinogalactan on Pharmacokinetics of “Guest” Drugs in Rats: For Example, Warfarin

    Directory of Open Access Journals (Sweden)

    Mikhail V. Khvostov

    2013-01-01

    Full Text Available A pharmacokinetic study of the warfarin (WF : arabinogalactan (AG complex with the 1 : 10 mass ratio after its intragastric introduction to Wistar rats at a dose of 5 mg/kg (WF dose in the complex was 0.5 mg/kg once a day for three days was conducted. It was found that Cmax, T1/2, and AUC of WF in the complex form were lower than after the introduction of blank WF at the same dose, but its elimination (Cl, MRT was much faster. Significant accumulation (Cmin and an abrupt increase in plasma concentration after the third introduction were observed for blank WF, whereas the complex showed a much more moderate increase in concentration at this point. However, despite obvious differences in pharmacokinetic parameters, the efficacies of both agents were virtually identical; the complex differed from blank WF by only 15%. This value is rather insignificant and does not impair its anticoagulant activity. Thus, we can conclude that introduction of the WF : AG complex is safe in terms of reduction of the bleeding risk and accumulation.

  20. Diet- or warfarin-induced vitamin K insufficiency elevates circulating undercarboxylated osteocalcin without altering skeletal status in growing female rats.

    Science.gov (United States)

    Haffa, A; Krueger, D; Bruner, J; Engelke, J; Gundberg, C; Akhter, M; Binkley, N

    2000-05-01

    To further characterize the skeletal role of vitamin K (K), markers of bone turnover, density, and strength were evaluated in rats with diet- or warfarin (W)-induced K insufficiency. One hundred two, 7-week-old, female rats were randomly assigned to low K (phylloquinone [K1], 20 microg/kg diet), control K (K1, 1300 microg/kg diet), low-dose W (W, 1.5 mg/kg control diet), or high-dose W plus K (W/K1, 10/100 mg/kg diet). Femur bone mineral content (BMC) and bone mineral density (BMD), plasma prothrombin time (PT) and prothrombin concentration (PC), and serum total alkaline phosphatase (ALP) and skeletal alkaline phosphatase (sALP) were measured at baseline and days 20, 40, 60, and 80. Serum total osteocalcin (OC) and undercarboxylated osteocalcin (ucOC) and femur length (FL) were measured at baseline and day 80. Left femur OC was measured and biomechanical testing of the right femur and third lumbar vertebral body was performed at day 80. Low dietary K elevated circulating ucOC (17% higher than control; p diet manipulation. This does not hinder peak bone mass attainment in female rats; however, W causes less newly synthesized OC to be deposited in bone.

  1. Pharmaceutical care for a patient with warfarin-induced autoimmune hepatitis%1例华法林诱导的严重自身免疫性肝炎的药学监护

    Institute of Scientific and Technical Information of China (English)

    刘维; 李璐; 胥婕; 张弨

    2016-01-01

    SUMMARY Herewereportedapatientwithwarfarin-inducedautoimmunehepatitis(AIH),andex-plored new concerns for the pharmaceutical care of warfarin.A 57-year-old woman was admitted to hospi-tal for repeated anorexia,abdominal pain and abnormal liver function.She received prosthetic heart valve replacement because of rheumatic heart disease,and had started warfarin medication since 2 years before.Her liver function was elevated with highest alanine aminotransferase 861 U/L, aspertate aminotransferase 604 U/L,and total bilirubin 1 06.7 μmol/L.Her anticoagulant therapy was switched to low molecular weight heparin and the liver function returned to normal.The liver function was elevated when she started to take warfarin again.The patient was then on liver protection therapy,and warfarin was stopped again for the liver biopsy for diagnosis reason.Through medication consultation and evalua-tion,pharmacists were invited to work together with the physicians and helped to differentiate the reason for abnormal liver function, and provided therapeutic suggestions. Also the pharmacists gained experiences in the treatment of AIH,and discovered a new and severe adverse drug reaction for warfarin. In treating this case,the pharmacists’active involvement into the treatment and evaluation of the effect on the patient reflected the advantage and importance of the multidisciplinary cooperation for pharmacists and physicians when complex diseases are faced.

  2. Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

    Science.gov (United States)

    Amin, Alpesh; Deitelzweig, Steve; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

    2014-01-01

    Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

  3. Quality of Anticoagulation Control in Preventing Adverse Events in Heart Failure Patients in Sinus Rhythm: A Warfarin Aspirin Reduced Cardiac Ejection Fraction Trial (WARCEF) Substudy

    Science.gov (United States)

    Homma, Shunichi; Thompson, John L.P.; Qian, Min; Ye, Siqin; Di Tullio, Marco R.; Lip, Gregory Y.H.; Mann, Douglas L.; Sacco, Ralph L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J.P.; Labovitz, Arthur J.; Buchsbaum, Richard; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

    2015-01-01

    Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. PMID:25850425

  4. Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?

    Science.gov (United States)

    O'Neil, William M; Welner, Sharon A; Lip, Gregory Y H

    2013-03-01

    Recent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54-1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73-2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.

  5. Chronic subdural hematoma in elderly patient with EDTA-dependent pseudothrombocytopenia recently treated with aspirin and warfarin: case report.

    Science.gov (United States)

    Tosa, Masato; Fujita, Hiroshi; Ishihama, Yumiko; Nishimura, Shigeko; Ide, Takafumi

    2014-01-01

    A 78-year-old man who had a history of myocardial and cerebral infarction and who was treated with aspirin and warfarin, presented with left chronic subdural hematoma. Cerebral computed tomography showed severe brain compression of hematoma with midline shift, indicating the need for emergent surgery. The hematology and clotting tests upon admission revealed severe thrombocytopenia (platelet count, 1.3 × 10(4)/μL) with normal clotting activity. Because platelet aggregation was evident in the smear, we re-examined the patient for hematology using tubes that contained heparin, showing also low platelet count (2.3 × 10(4)/μL). The day on admission, we performed irrigation and drainage of the chronic subdural hematoma through single burr-hole craniostomy. During surgery, we used 10 units of platelet concentrates (PCs) for the reason that the patient was taking aspirin and coagulopathy derived from low platelet count could not be excluded. After surgery, we re-evaluated the hematology of the blood stored in tubes that contained ethylenediaminetetraacetic acid (EDTA) with or without kanamycin (KM). Treatment with KM dissociated EDTA-induced platelet aggregation and revealed platelet counts with highest accuracy (no KM treatment, 1.3 × 10(4)/μL; KM treatment, 15.2 × 10(4)/μL). This phenomenon is called EDTA-Dependent Pseudothrombocytopenia (PTCP) defined as falsely low platelet counts reported by automated hematology analyzers due to platelet aggretgation. Awareness of the phenomenon will enable neurosurgeons to manage patients with PTCP appropriately and clinical laboratory especially in emergency hospital is recommended to prepare for the hematological tubes being added KM in routine analysis, resulting in preventing mistaken diagnosis.

  6. Protocol for Cerebral Microbleeds during the Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin Therapy in Stroke Patients with Nonvalvular Atrial Fibrillation (CMB-NOW) Study: Multisite Pilot Trial.

    Science.gov (United States)

    Takizawa, Shunya; Tanaka, Fumiaki; Nishiyama, Kazutoshi; Hasegawa, Yasuhiro; Nagata, Eiichiro; Mizuma, Atsushi; Yutani, Sachiko; Nakayama, Taira; Kobayashi, Hiroyuki; Yanagimachi, Noriharu; Okazaki, Takashi; Kitagawa, Kazuo

    2015-09-01

    Anticoagulants are widely used to prevent recurrence of ischemic stroke in patients with nonvalvular atrial fibrillation, but in some patients, they also cause bleeding, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in warfarin-treated patients with multiple CMBs. Longitudinal study suggested that the presence of CMBs at baseline is a predictor of new CMBs in warfarin-treated patients. However, there has been no study on the progression of CMBs in patients receiving the non-vitamin K antagonist oral anticoagulants (NOACs). This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. We will enroll 200 patients with at least 1 CMB detected by 1.5 T magnetic resonance imaging (T2(∗)-weighted imaging) at baseline and who have received NOACs or warfarin for at least 12 months. Primary end point is the proportion of subjects with an increased number of CMBs at month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs for preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that on primary prevention of ischemic stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. Influence of CYP2C9 and VKORC1 on patient response to warfarin: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Andrea L Jorgensen

    Full Text Available BACKGROUND: Warfarin is a highly effective anticoagulant however its effectiveness relies on maintaining INR in therapeutic range. Finding the correct dose is difficult due to large inter-individual variability. Two genes, CYP2C9 and VKORC1, have been associated with this variability, leading to genotype-guided dosing tables in warfarin labeling. Nonetheless, it remains unclear how genotypic information should be used in practice. Navigating the literature to determine how genotype will influence warfarin response in a particular patient is difficult, due to significant variation in patient ethnicity, outcomes investigated, study design, and methodological rigor. Our systematic review was conducted to enable fair and accurate interpretation of which variants affect which outcomes, in which patients, and to what extent. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive search strategy was applied and 117 studies included. Primary outcomes were stable dose, time to stable dose and bleeding events. Methodological quality was assessed using criteria of Jorgensen and Williamson and data synthesized in meta-analyses using advanced methods. Pooled effect estimates were significant in most ethnic groups for CYP2C9*3 and stable dose (mutant types requiring between 1.1(0.7-1.5 and 2.3 (1.6-3.0mg/day. Effect estimates were also significant for VKORC1 and stable dose for most ethnicities, although direction differed between asians and non-asians (mutant types requiring between 0.8(0.4-1.3 and 1.5(1.1-1.8mg/day more in asians and between 1.5(0.7-2.2 and 3.1(2.7-3.6mg/day less in non-asians. Several studies were excluded due to inadequate data reporting. Assessing study quality highlighted significant variability in methodological rigor. Notably, there was significant evidence of selective reporting, of outcomes and analysis approaches. CONCLUSIONS/SIGNIFICANCE: Genetic associations with warfarin response vary between ethnicities. In order to achieve unbiased

  8. Motion of left atrial appendage as a determinant of thrombus formation in patients with a low CHADS2 score receiving warfarin for persistent nonvalvular atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Ono Koji

    2012-12-01

    Full Text Available Abstract Background The aim of this study was to define the independent determinants of left atrial appendage (LAA thrombus among various echocardiographic parameters measured by Velocity Vector Imaging (VVI in patients with nonvalvular atrial fibrillation (AF receiving warfarin, particularly in patients with a low CHADS2 score. Methods LAA emptying fraction (EF and LAA peak longitudinal strain were measured by VVI using transesophageal echocardiography in 260 consecutive patients with nonvalvular persistent AF receiving warfarin. The patients were divided into two groups according to the presence (n=43 or absence (n=217 of LAA thrombus. Moreover, the patients within each group were further divided into subgroups according to a CHADS2 score ≤1. Results Multivariate logistic regression analysis showed that LAAEF was an independent determinant of LAA thrombus in the subgroup of 140 with a low CHADS2 score. Receiver operating characteristics curve analysis showed that an LAAEF of 21% was the optimal cutoff value for predicting LAA thrombus. Conclusions LAA thrombus formation depended on LAA contractility. AF patients with reduced LAA contractile fraction (LAAEF ≤21% require strong anticoagulant therapy to avoid thromboembolic events regardless of a low CHADS2 score (≤1.

  9. Delayed Bleeding and Pelvic Haematoma after Low-Energy Osteoporotic Pubic Rami Fracture in a Warfarin Patient: An Unusual Cause of Abdominal Pain

    Directory of Open Access Journals (Sweden)

    Andrea Sandri

    2014-01-01

    Full Text Available Introduction. Acute abdominal pain may be the presenting symptom in a wide range of diseases in the elderly. Acute abdominal pain related to a delayed bleeding and pelvic haematoma after a low-energy pubic rami fracture is rare and can have important consequences; to the best of our knowledge, only one case has been previously described. Case Report. We present an unusual case of an 83-year-old woman taking warfarin for atrial fibrillation, admitted to the Emergency Department (ED with acute abdominal pain and progressive anemia related to a delayed bleeding and pelvic haematoma 72 hours after a low-energy osteoporotic pubic rami fracture. Warfarin was withheld, anticoagulation was reversed by using fresh frozen plasma and vitamin K, and concentrated red blood cells were given. Haemoglobin level gradually returned to normal with a progressive resorption of the haematoma. Conclusion. Delayed bleeding and pelvic haematoma after osteoporotic pubic rami fracture should be considered in the differential diagnosis of acute abdominal pain in the elderly. This case indicates the need for hospital admission, careful haemodynamic monitoring, and early identification of bleeding in patients with “benign” osteoporotic pubic rami fracture, especially those receiving anticoagulants, to provide an adequate management and prevent severe complications.

  10. Novel mutations in the VKORC1 gene of wild rats and mice – a response to 50 years of selection pressure by warfarin?

    Directory of Open Access Journals (Sweden)

    Jäkel Thomas

    2009-02-01

    Full Text Available Abstract Background Coumarin derivatives have been in world-wide use for rodent pest control for more than 50 years. Due to their retarded action as inhibitors of blood coagulation by repression of the vitamin K reductase (VKOR activity, they are the rodenticides of choice against several species. Resistance to these compounds has been reported for rodent populations from many countries around the world and poses a considerable problem for efficacy of pest control. Results In the present study, we have sequenced the VKORC1 genes of more than 250 rats and mice trapped in anticoagulant-exposed areas from four continents, and identified 18 novel and five published missense mutations, as well as eight neutral sequence variants, in a total of 178 animals. Mutagenesis in VKORC1 cDNA constructs and their recombinant expression revealed that these mutations reduced VKOR activities as compared to the wild-type protein. However, the in vitro enzyme assay used was not suited to convincingly demonstrate the warfarin resistance of all mutant proteins Conclusion Our results corroborate the VKORC1 gene as the main target for spontaneous mutations conferring warfarin resistance. The mechanism(s of how mutations in the VKORC1 gene mediate insensitivity to coumarins in vivo has still to be elucidated.

  11. Cost-effectiveness of clopidogrel plus aspirin for stroke prevention in patients with atrial fibrillation in whom warfarin is unsuitable.

    Science.gov (United States)

    Coleman, Craig I; Straznitskas, Andrew D; Sobieraj, Diana M; Kluger, Jeffrey; Anglade, Moise W

    2012-04-01

    Guidelines for atrial fibrillation (AF) recommend clopidogrel plus aspirin as an alternative stroke prevention strategy in patients in whom warfarin is unsuitable. A Markov model was conducted from a Medicare prospective using data from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events-A (ACTIVE-A) trial and other published studies. Base-case analysis evaluated patients 65 years old with AF, a CHADS(2) (congestive heart failure, 1 point; hypertension defined as blood pressure consistently >140/90 mm Hg or antihypertension medication, 1 point; age ≥75 years, 1 point; diabetes mellitus, 1 point; previous stroke or transient ishemic attack, 2 points) score of 2, and a lower risk for major bleeding. Patients received clopidogrel 75 mg/day plus aspirin or aspirin alone. Patients were followed for up to 35 years. Outcomes included quality-adjusted life-years (QALYs), costs (in 2011 American dollars), and incremental cost-effectiveness ratios. Quality-adjusted life expectancy and costs were 9.37 QALYs and $88,751 with clopidogrel plus aspirin and 9.01 QALYs and $79,057 with aspirin alone. Incremental cost-effectiveness ratio for clopidogrel plus aspirin was $26,928/QALY. With 1-way sensitivity analysis using a willingness-to-pay threshold of $50,000/QALY, clopidogrel plus aspirin was no longer cost effective when the CHADS(2) score was ≤1, major bleeding risk with aspirin was ≥2.50%/patient-year, the relative risk decrease for ischemic stroke with clopidogrel plus aspirin versus aspirin alone was plus aspirin was cost effective in 55% and 73% of 10,000 iterations assuming willingness-to-pay thresholds of $50,000 and $100,000/QALY. In conclusion, clopidogrel plus aspirin appears cost-effective compared to aspirin alone for stroke prevention in patients with AF with a CHADS(2) of ≥2 and a lower risk of bleeding. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case–control study

    Directory of Open Access Journals (Sweden)

    H-Y Chou Sherry

    2012-12-01

    Full Text Available Abstract Background Recombinant factor VIIa (rFVIIa may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH, FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP and vitamin K alone. Methods We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%, deep venous thrombosis (DVT or pulmonary embolism (PE (22% vs 18%, coronary artery disease (CAD (38% vs 32%, and abnormal electrocardiogram (EKG (78% vs 85%. Troponin elevation following wICH was prevalent in both groups (47% vs 41%. Clinically significant myocardial infarction (MI, defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52. Past history of CAD (p=0.0061 and baseline abnormal EKG (p=0.02 were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18 and ischemic stroke (2% vs 0%; p=0.38 were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001 and 6 hours (p Conclusions Pre

  13. LBA-2 A randomized trial of long-term tinzaparin, a Low Molecular Weight Heparin (LMWH), versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients-the CATCH study

    NARCIS (Netherlands)

    Lee, Agnes Y.Y.; Kamphuisen, Pieter W.; Meyer, Guy; Bauersachs, Rupert; Janas, Mette S.; Jarner, Mikala F.; Khorana, Alok A.

    2014-01-01

    Background Patients with cancer and VTE have a substantial risk of recurrent VTE. LMWH reduces the risk of symptomatic, recurrent VTE compared with warfarin and is recommended as the preferred anticoagulant by consensus guidelines. However, the evidence is based largely on a single, open-label rando

  14. A quantitative approach to the determination of drug release from reverse-phase evaporation lipid vesicles. The influence of sodium ion-pair formation on warfarin partitioning and permeability

    NARCIS (Netherlands)

    Janssen, L.H.M.; Cools, A.A.

    1984-01-01

    The influence of sodium ion-pair formation on warfarin partitioning and permeability has been investigated using reverse-phase evaporation lipid vesicles. An experimental method for the isolation of the vesicles having known amounts of encapsulated drug has been described. The partitioning of warfar

  15. CYP2C9和VKORC1基因多态性对华法林剂量的影响%Effect of Polymorphisms of CYP2C9 and VKORC1 on Warfarin Dosage

    Institute of Scientific and Technical Information of China (English)

    郑红艳

    2011-01-01

    Warfarin is widely used as an oral anticoagulant in clinical practice.It has a narrow therapeutic range but a large individual variation.Especially, it leads to serious bleeding complications easily in early treatment.The rational and safe use of warfarin has been becoming a key problem in clinical practice.The efficacy of warfarin is affected by many factors, and the genetic polymorphism of hereditary factors is prominent.In recent years, with the development of pharmacogenomics, the studies show that the genetic polymorphisms of related genes in pharmacokinetics and pharmacodynamics result in interindividual variation in warfarin.We review the effects of genetic polymorphisms, such as CYP2C9 and VKORC1 ,on drug response and therapeutic efficacy of warfarin.%华法林是临床上广泛使用的口服抗凝药物,其治疗范围窄,个体差异大,尤其在治疗初期,易导致严重的出血并发症,如何合理、安全使用成为国内外研究者关注的重点和难点.华法林的疗效受多种因素的影响,以遗传因素中基因多态性较为突出.近年来,随着药物基因组学的快速发展,研究发现药动学和药效学多个相关基因的多态性造成了华法林的个体差异.现从基因多态性角度综述CYP2C9和VKORC1基因的遗传变异对华法林药物反应差异的影响.

  16. Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: potential role of protein Z as a powerful determinant of coagulation assays.

    Science.gov (United States)

    Choi, Qute; Kim, Ji-Eun; Hyun, Jungwon; Han, Kyou-Sup; Kim, Hyun Kyung

    2013-07-01

    The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro. The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 1例抗菌药物与华法林相互作用的病例分析%One case analysis of antibacterials interaction with Warfarin

    Institute of Scientific and Technical Information of China (English)

    谭娜; 蔡佳; 谭昀杜熙

    2015-01-01

    目的:通过临床药师参与1例感染性心内膜炎抗感染治疗期间华法林剂量调整的药学实践,探讨其在临床治疗中发挥的作用.方法:临床药师依靠药学知识尤其是药动学优势,抗菌药物治疗期间与医师一起共同参与药物治疗监测及制定华法林给药剂量方案.结果:经过反复调整华法林剂量,最终达到满意抗凝目标值.结论:临床药师参与临床治疗实践,有利于提高药物治疗水平.%Objective:To explore the role of clinical pharmacists in clinical treatment by adjusting the dose of warfarin during the period of anti-infective treatment in a patient with infective endocarditis.Methods: The clinical pharmacists collaborated with clinicians monitored drug therapy and adjusted the dose of warfarin during the period of anti-infective treatment utilizing their pharmaceutical knowledge, especially pharmacokinetic knowledge.Results:After repeatedly adjusted the dose of warfrin, and eventually reached a satisfactory target value of anticoagulation.Conclusion: Clinical pharmacists involvement in clinical practice is helpful for improving the level of drug treatment.

  18. Discussion on standard use of warfarin and related clinical pharmacy practice%探讨华法林用药规范和开展相应临床药学工作的必要性

    Institute of Scientific and Technical Information of China (English)

    李玥; 陈敏玲; 张顺国; 李岚; 蒋樾廉; 贡沁燕

    2011-01-01

    目的:提高临床医师对心脏人工机械瓣膜置换术后华法林抗凝用药规范的认识.方法:检索已有的华法林抗凝治疗循证医学文献,以此评价一名7个月先天性心脏病患儿换瓣术后,住院期间低分子量肝素、华法林和维生素K1的应用过程.结果:术后第1~4天国际标准化比值(international normalized ratio,INR)均在正常参考值范围内.术后第6天INR达抗凝目标值,静脉滴注维生素K12 mg后,INR降到正常参考值.结论:临床医师对华法林抗凝过度的误判以及应用维生素K1处置不妥,且该病例可能存在华法林抵抗现象,说明了制定华法林抗凝治疗用药规范的重要性及开展相应临床药学工作的必要性.%Objective: To enhance the understanding of guidelines for anticoagulant therapy with warfarin after mechanical valve replacement. Methods: We retrieved the evidence-based medicine literature of anticoagulant therapy with warfarin, so as to evaluate the management of a 7-month-old patient with congenital heart disease cured by low molecular weight heparin( LM-WH), warfarin and vitamin K, after mechanical valve replacement during in hospital. Results: The international normalized ra-tio(INR) of the patient was in the reference values from the first to fourth day after operation. The INR reached the target of anticoagulation at the sixth day after operation. Vitamin K, (2 mg) was given by intravenously guttae, then the INR dropped to the reference values. Conclusion: Clinical doctors have misjudged the over-anticoagulation of the warfarin and incorrectly used the vitamin Ki. Warfarin resistance may have existed in this case. So it is necessary to carry out clinical pharmacy practice and is important to carry out standard of anticoagulant therapy with warfarin.

  19. CYP4F2基因多态性与华法林维持剂量关系的研究进展%Research progress in association between CYP4F2 gene polymorphism and warfarin maintenance dose

    Institute of Scientific and Technical Information of China (English)

    谢爽; 李一石

    2011-01-01

    Currently, warfarin is the most widely used oral anticoagulant in clinic. Since warfarin has narrow therapeutic window and significant individual differences in dose, it easily leads to complications due to improper anticoagulate therapy. In recent 3 years, as the rapid development of pharmacogenomics, it has been found that CYP4F2 (cytochrome P450, family 4, subfamily F, polypeptide 2) gene polymorphism ( rs2108622) relates to warfarin individual dosage requirement. We reviewed research progress in association between CYP4F2 gene polymorphism. Most studies found that CYP4F2 gene polymorphism relates to warfarin dose, and the mutant T allele was associated with higher warfarin dose requirement, CYP4F2 * 3 polymorphism can explain 1% ~ 10% warfarin individual dosage difference.%华法林是目前临床上应用最广泛的口服抗凝药,其治疗安全范围窄,剂量个体差异大,临床应用中容易出现抗凝不当所致的并发症.近3年来,随着药物基因组学的快速发展,发现细胞色素P450酶4F2(CYP4F2)基因多态性(rs2108622)与华法林个体剂量差异相关.本文综述了近3年来在不同人种中进行的有关CYP4F2*3(rs2108622)与华法林的维持剂量关系的研究.大多数研究发现CYP4F2基因多态性与华法林维持剂量存在相关性,其中突变的T等位基因与华法林高剂量相关;CYP4F2*3可以解释1%~10%华法林剂量个体差异.

  20. Research progress of warfarin in patients with atrial fibrillation undergoing dialysis%华法林在透析心房颤动患者中研究状况

    Institute of Scientific and Technical Information of China (English)

    缪达; 阳国平

    2016-01-01

    Kidney dysfunction can increase the incidence of atrial fibri-llation, the risk of stroke and bleeding increase significantly in patients with atrial fibrillation undergoing dialysis.Anticoagulantion treatment has been shown to reduce the risk of stroke.Warfarin is the most widely used anticoagulant in clinical practice, whether the use of warfarin in patients with atrial fibrillation undergoing dialysis can benefit is still in controver-sy.This review summarizes the recent researches on warfarin in patients with atrial fibrillation undergoing dialysis, analyzes the advice in guide-line for the management of patients with atrial fibrillation, and hopes to provide a reference for reasonable use of warfarin in patients with atrial fi-brillation undergoing dialysis.%肾功能异常可增加心房颤动发病率,透析的心房颤动患者卒中风险和出血风险显著升高。抗凝治疗可降低心房颤动患者卒中风险,华法林是临床常用口服抗凝药,在透析的心房颤动患者中使用华法林能否获益仍存在争议。本文汇总了近年来华法林在透析的心房颤动患者中的研究,分析了各国心房颤动抗凝指南的建议,旨在为华法林在透析的心房颤动患者中合理应用提供参考。

  1. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes.

    Science.gov (United States)

    Hylek, Elaine M; Held, Claes; Alexander, John H; Lopes, Renato D; De Caterina, Raffaele; Wojdyla, Daniel M; Huber, Kurt; Jansky, Petr; Steg, Philippe Gabriel; Hanna, Michael; Thomas, Laine; Wallentin, Lars; Granger, Christopher B

    2014-05-27

    This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding. Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model. The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk. Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

    Science.gov (United States)

    Saji, Naoki; Kimura, Kazumi; Tateishi, Yohei; Fujimoto, Shigeru; Kaneko, Nobuyuki; Urabe, Takao; Tsujino, Akira; Iguchi, Yasuyuki

    2016-11-01

    The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

  3. Evaluation of Subdivision of Warfarin Sodium Tablets from 3 Enterprises%3厂家华法林钠片分剂量的评价

    Institute of Scientific and Technical Information of China (English)

    刘元江; 缪经纬; 邓欣; 詹金陶; 刘其东

    2012-01-01

    OBJECTIVE: To evaluate rationality of splitting warfarin sodium tablets from 3 enterprises. METHODS: Tablet cutter, scissor and knife were used to divide whole tablet from enterprise A (imported uncoated tablets), B (domestic sugar-coated tablets) and C (domestic film-coated tablets) into half and quarter parts by a student. For one third and one fifth parts, the method scissor by 2 students and pulverizing by 2 pharmacists were applied (n=30) , meanwhile European Pharmacopeia 6.0(EP 6.0) and other standards were adopted to evaluate the accuracy of subdivision of half and quarter parts and friability of all the subdivision. The disintegration time of tablets from 3 enterprises was investigated. RESULTS: The accuracy of subdivision of Warfarin sodium tablets from 3 enterprises could not met the requirement specified in EP 6.0. There was no significant difference in the pass rate of subdivision of half and quarter parts among 3 methods, there was no significant difference in the pass rate of subdivision between 2 students (except fifth parts) or 2 pharmacists. As to friability test for equal parts, enterprise A met the standard while enterprises B and C not. The disintegration time were 3, 29 and 23 min for 3 enterprises. CONCLUSION: It is not rational to subdivide Warfarin sodium tablets by above methods.%目的:评价3厂家华法林钠片分剂量的合理性.方法:对A(进口,未包衣)、B(国产,糖衣片)、C(国产,薄膜衣片)厂家的华法林钠片进行分剂量,分别由1名学生用切药器、剪刀、小刀将整片进行二、四等分;由另外2名学生用剪刀和2名药师用磨粉分包将整片进行三、五等分(n=30).参照《欧洲药典》第6版,对二、四等分片进行分剂量准确性评价,对二、三、四、五等分片进行等分片脆碎度评价,并考察3厂家片剂的崩解时限.结果:3厂家二、三、四、五等分分剂量准确性均不符合《欧洲药典》规定.3种方法二、四等分分

  4. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

    Science.gov (United States)

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

  5. Cognitive function in ambulatory patients with systolic heart failure: insights from the warfarin versus aspirin in reduced cardiac ejection fraction (WARCEF trial.

    Directory of Open Access Journals (Sweden)

    Susan Graham

    Full Text Available We sought to determine whether cognitive function in stable outpatients with heart failure (HF is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance. The mean (SD for the MMSE was 28.6 (2.0, with 64 (3.1% of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001, but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure.

  6. Cognitive function in ambulatory patients with systolic heart failure: insights from the warfarin versus aspirin in reduced cardiac ejection fraction (WARCEF) trial.

    Science.gov (United States)

    Graham, Susan; Ye, Siqin; Qian, Min; Sanford, Alexandra R; Di Tullio, Marco R; Sacco, Ralph L; Mann, Douglas L; Levin, Bruce; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Mohr, J P; Labovitz, Arthur J; Lip, Gregory Y H; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

    2014-01-01

    We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure.

  7. The potential use of decision analysis to support shared decision making in the face of uncertainty: the example of atrial fibrillation and warfarin anticoagulation.

    Science.gov (United States)

    Robinson, A; Thomson, R G

    2000-12-01

    The quality of patient care is dependent upon the quality of the multitude of decisions that are made daily in clinical practice. Increasingly, modern health care is seeking to pursue better decisions (including an emphasis on evidence-based practice) and to engage patients more in decisions on their care. However, many treatment decisions are made in the face of clinical uncertainty and may be critically dependent upon patient preferences. This has led to attempts to develop decision support tools that enable patients and clinicians to make better decisions. One approach that may be of value is decision analysis, which seeks to create a rational framework for evaluating complex medical decisions and to provide a systematic way of integrating potential outcomes with probabilistic information such as that generated by randomised controlled trials of interventions. This paper describes decision analysis and discusses the potential of this approach with reference to the clinical decision as to whether to treat patients in atrial fibrillation with warfarin to reduce their risk of stroke.

  8. Accuracy of the CoaguChek XS for point-of-care international normalized ratio (INR) measurement in children requiring warfarin.

    Science.gov (United States)

    Bauman, Mary E; Black, Karina L; Massicotte, Mary P; Bauman, Michelle L; Kuhle, Stefan; Howlett-Clyne, Susan; Cembrowski, George S; Bajzar, Laszlo

    2008-06-01

    Point-of-care INR (POC INR) meters can provide a safe and effective method for monitoring oral vitamin K antagonists (VKAs) in children. Stollery Children's Hospital has a large POC INR meter loan program for children requiring oral VKAs. Our protocol requires that POC INR results be compared to the standard laboratory INR for each child on several consecutive tests to ensure accuracy of CoaguChek XS (Roche Diagnostics, Basel Switzerland) meter. It was the objective of the study to determine the accuracy of the CoaguChek XS by comparing whole blood INR results from the CoaguChek XS to plasma INR results from the standard laboratory in children. POC INR meter validations were performed on plasma samples from two time points from 62 children receiving warfarin by drawing a venous blood sample for laboratory prothrombin (PT)-INR measurements and simultaneous INR determinations using the POC-INR meter. Agreement between CoaguChek XS INR and laboratory INR was assessed using Bland-Altman plots. Bland-Altman's 95% limits of agreement were 0.11 (-0.20; 0.42) and 0.13 (-0.22; 0.48) at the two time points, respectively. In conclusion, the CoaguChek XS meter appraisal generates an accurate and precise INR measure in children when compared to laboratory INR test results.

  9. Varfarina previne obstruções venosas pós-implante de dispositivos cardíacos em pacientes de alto risco: análise parcial Warfarin prevents venous obstruction after cardiac devices implantation in high-risk patients: partial analysis

    Directory of Open Access Journals (Sweden)

    Kátia Regina da Silva

    2008-12-01

    Full Text Available OBJETIVOS: Avaliar a utilidade da varfarina na prevenção dessas complicações nos pacientes de alto risco. MÉTODOS: Estudo clínico prospectivo, randomizado, cego, em pacientes submetidos ao primeiro implante transvenoso de DCEI, com FEVEOBJECTIVES: To evaluate the efficacy of prophylactic use of warfarin in patients with high risk of lead-associated thrombosis. METHODS: Clinical, prospective, randomized and blinded study, in patients submitted to first transvenous leads implantation with LVEF <0.40 and/or previous ipsilateral temporary pacing. After device implantation, patients were randomly assigned to placebo or warfarin. Periodical clinical and laboratorial evaluations were performed to anticoagulant management. After a six-month period, every patient was submitted to a digital subtraction venography. From February 2004 to November 2006, 101 patients underwent randomization. Baseline characteristics were similar in both groups (P=NS. RESULTS: Venographic analysis showed 31.4% of venous obstructions in patients assigned to warfarin as compared with 57.1% in patients assigned to placebo (RR= 0.57 [95% CI, 0.33 to 0.98]; P=0.015. In the warfarin group, 72% of the PT/INR tests were in therapeutic INR range. Only one patient required warfarin discontinuation and cross-over to placebo group due to gastrointestinal bleeding. CONCLUSIONS: These preliminary results showed that the anticoagulation therapy has been safe and reduced the frequency of venous thrombosis after transvenous cardiac devices implantation in high risk patients.

  10. 179例心房颤动住院患者华法林应用情况∗%Current Application of Warfarin in 179 Hospitalized Patients with Atrial Fibrillation

    Institute of Scientific and Technical Information of China (English)

    吴玥; 彭燕; 戎佩佩; 李萌; 周本宏

    2015-01-01

    Objective To retrospectively analyzed the current application of warfarin in hospitalized patients with non-valvular atrial fibrillationand ( NVAF), explore the key role of clinical pharmacists in warfarin medication. Methods A retrospective survey of anticoagulant therapy for 179 hospitalized patients with non-valvular atrial fibrillation in Renming Hospotal of Wuhan University from January to December 2013 was retrived,including the usage of warfarin for NVAF and new-onset atrial fibrillation,dosage,international normalized ratio(INR),hemorrhage event and so on.The simple factor like the age,complicated chronic diseases and previous cerebrovascular events on the use of warfarin was explored. Results The total response rate to anticoagulants was 85.6% for patients with high risk of stroke(27.3% with warfarin and 58.3% with antiplatelet therapy),who are recommended to use warfarin,patient were treated with anti-thrombotic therapy.The total of 19.1% of the patients with new-onset atrial fibrillation used warfarin as therapy.The whole monitoring rate of INR was 89.8%,and the good control rate was 11.9%. Univariate analysis showed that some high risk factors such as age and high blood pressure affected the usage of warfarin. Conclusion The anti-thrombotic therapy for NVAF patients in the hospital is good,but usage of warfarin for those with new-onset atrial fibrillation is low,which couldn't reach the INR standard. More attention should be taken by the clinic pharmacists in effective managing the use of anticoagulant to build a safe,economic and effective medication system for warfarin application.%目的:回顾性分析非瓣膜性心房颤动(房颤)住院患者华法林应用情况,探讨临床药师在华法林治疗中的作用。方法查阅武汉大学人民医院2013年1—12月非瓣膜性房颤住院患者病历179份,对华法林使用率、抗血栓治疗情况、华法林用药剂量、国际标准化比值(INR)监控率、不良反应等情况进行

  11. The Effects of Compound Danshen Dripping Pills on the Pharmacodynamics and Pharmacokinetics of Warfarin in Humans%复方丹参滴丸对华法林在人体内药动学和药效学的影响

    Institute of Scientific and Technical Information of China (English)

    易丹; 罗晓波; 陆向红; 罗圣平; 周于禄

    2013-01-01

    目的 研究复方丹参滴丸对华法林在人体内药动学和药效学的影响,以及单独服用复方丹参滴丸4 周后对凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)的影响.方法 采用随机、单盲、双周期交叉、安慰剂对照试验设计.12 名男性健康志愿者随机分为2 组(6 人/ 组),连续5 周每日分别服用复方丹参滴丸(10 片,每天3 次)或安慰剂(10 片,每天3 次);d29 口服单剂量华法林5 mg;第2 周期2 组交叉服用安慰剂或复方丹参滴丸,其余给药方案不变.按要求收集志愿者血样,分别以高效液相色谱法(HPLC)测定华法林的血药浓度以及半自动血凝仪测定常见凝血指标.结果 合用复方丹参滴丸后,华法林的药动学参数cmax、AUC0~144、AUC0~∞、t1/2显著增加(P <0.05),CL/F显著减小(P <0.05),tmax和V/F 没有显著变化;华法林的药效学参数发生显著变化.单独服用复方丹参滴丸4 周后,PT和APTT 均发生显著变化.结论复方丹参滴丸可影响华法林的药动学和药效学;单独服用复方丹参滴丸4 周对凝血功能有显著影响.%Objective To study the effect of Danshen Dripping Pills on the pharmacokinetics and pharmacodynamics of warfarin, and to assess whether or not Danshen Dripping Pills alone has any anticoagulant activity. Methods A randomized, double-blind, placebo-controlled, two-way cross-over trial was designed.Twelve male healthy volunteers (6 person/group) were randomized to receive either Danshen Dripping Pills in the first treatment period and placebo in the second treatment period, or vice versa. In addition to their randomized trentment, all volunteers received a single dose of 5 mg warfarin on d 29 of each treatment period. Blood samples for assessment were taken at frequent intervals during each treatment period. Results Administration of Danshen Dripping Pills significantly increased cmax、AUC0~144、AUC0~∞、t1/2 and significantly decreased CL/F of warfarin

  12. Influence of pharmacist intervention on patients′knowledge of anticoagulation therapy with warfarin%药师干预对华法林抗凝患者治疗认知度的影响研究

    Institute of Scientific and Technical Information of China (English)

    蒋捷; 谢秋芬; 向倩; 王梓凝; 霍东波; 曹利佳; 周双; 周颖; 崔一民

    2015-01-01

    ;Objective To investigate the influence of pharmacist inter-vention on patients′knowledge of anticoagulation therapy with warfarin . Methods Two hundred sixteen patients who were admitted to cardiovas-cular wards and were prescribed anticoagulation therapy with warfarin from October 2013 to August 2014 were included in the study .According to the ward they stayed , patients were divided into control group ( Cardiology ward No1.) and intervention group ( Cardiology ward No 2.) . In the control group , physicians and nurses introduced anticoagulation knowledge for the patients as usual , while intervention group received medication education and guidance on warfarin use by pharmacists .All patients of two groups filled out an assessment questionnaire about warfa-rin anticoagulation at discharge ( outpoint =13 ) .If any answer to the questions was wrong , pharmacists would educate them again .The score of the questionnaire were compared between the two groups . Results The intervention group enrolled 112 patients while the control group enrolled 104 patients. Scores of assessment questionnaire at discharge of the intervention group and the control group were (10.50 ±2.24) vs (8.08 ±2.61) respectively,with statistical difference ( P <0.05 ) .Conclusion Knowledge of warfarin therapy was much better in patients who received pharmacist intervention than patients who received usual care . Integrated management model with pharmacist interventions can improve patients′cognition in anticoagulation therapy with warfarin .%目的:探讨药师干预对华法林抗凝患者治疗认知度的影响。方法选取2013年10月至2014年8月在我院心血管内科病房住院的口服华法林抗凝患者216例为研究对象,按照病区分为对照组(心内科一病房)和干预组(心内科二病房),对照组由医师及护士介绍华法林抗凝知识,干预组接受药师关于华法林抗凝的用药教育和指导。在出院时,2组患者均填

  13. Development of warfarin-related pharmacogenomics and its prospect of clinical application%华法林药物基因组学的发展及其临床应用前景

    Institute of Scientific and Technical Information of China (English)

    吴炯; 邬升超(综述); 郭玮; 潘柏申(审校)

    2014-01-01

    华法林是临床广泛使用的口服抗凝药物。由于自身狭窄的有效抗凝治疗范围以及个体间每日用药剂量的显著差异,困扰着许多患者和临床医生。近年来,许多研究均报道基因多态性是引起华法林个体间用药剂量差异的主要因素之一。部分学者建立基于药物基因组学的剂量方程,并在进行验证,评估其临床价值。本文综述了华法林相关药物基因组学的国内外最新进展,为进一步针对华法林的临床研究提供参考依据。%Warfarin,a commonly prescribed anticoagulant,has warried lots of patients and doctors because of its narrow therapeutic range and large interindividual variability in daily dose.During recent years,many studies focus on genetic polymorphisms,regarding it as one of the main effects which lead to dose difference between individuals.Some of them established and verified pharmacogenetic-based warfarin-dosing algorithms and evaluated the clinical significance.Our review exhibits the latest development of warfarin-related pharmacogenomics home and abroad,in order to provide references for further clinical studies.

  14. Interaction between ticlopidine or warfarin or cardioaspirin with a highly standardized deterpened Ginkgo biloba extract (VR456) in rat and human.

    Science.gov (United States)

    Di Pierro, Francesco; Rinaldi, Francesco; Lucarelli, Maurizio; Rossoni, Giuseppe

    2010-12-01

    Ginkgo biloba is available in Europe as an over-the-counter drug and it is reported to cause hemorrhage when co-administered with other anti-platelet agents. We set out to study the interactions of ticlopidine with Ginkgo biloba extract or VR456, a new highly standardized deterpened extract from Ginkgo biloba leaves. Male Wistar rats were used to study the effects of ticlopidine (50-100 mg/kg/day), given alone and in combination for 5 days with Ginkgo biloba extract (50 mg/kg/day) or VR456 (50 mg/kg/day), on bleeding time and ex vivo ADP-induced platelet aggregation measurements. In addition, human studies were performed with the compounds under investigation. Combined treatment of ticlopidine and undeterpened Ginkgo biloba extract increased anti-platelet effect and prolonged the bleeding time in the rat. On the contrary, the combination treatment of ticlopidine and VR456 increased anti-platelet effect but did not prolong bleeding time. Moreover, daily administration of 360 mg of VR456 for 14 days to ticlopidine-treated humans did not highlight any unwanted effect and did not alter PT/INR and PTT parameters. Same results have been also obtained in warfarin or in cardioaspirin-treated patients. These data point out the clear role played by the terpenoid, PAF-antagonist fraction of Ginkgo biloba extract in affecting bleeding risk in anticoagulant-treated subjects and suggest VR456 as a possible option treatment in geriatric people subjected to anticoagulant treatment where the use of standard Ginkgo biloba extracts are discouraged.

  15. Acute Myocardial Infarction Due to Coronary Artery Embolism in a 22-Year-Old Woman with Mitral Stenosis with Atrial Fibrillation Under Warfarinization: Successful Management with Anticoagulation.

    Science.gov (United States)

    Sinha, Santosh Kumar; Jha, Mukesh Jitendra; Razi, Mahmadula; Chaturvedi, Vikash; Erappa, Yatish Besthenahalli; Singh, Shravan; Mishra, Vikas; Khanra, Dibbendhu; Singh, Karandeep

    2017-04-07

    BACKGROUND Coronary artery embolization is an exceedingly rare cause of myocardial infarction, but a few cases in association with prosthetic mechanical valves have been reported. We report a case of embolic myocardial infarction caused by a thrombus in the left atrium with deranged coagulation profile in a patient with critical mitral stenosis under warfarinization. CASE REPORT A 22-year-old woman was taken to the catheterization lab for early coronary intervention in lieu of non-ST elevation myocardial infarction. Electrocardiography showed T↓ in V1 to V4, and atrial fibrillation with controlled ventricular rate. Coronary angiography showed total occlusion of the mid-left anterior descending artery with thrombus. After upstream treatment with tirofiban, the apparent thrombus was dislodged distally while passing a BMW wire. No abnormalities were seen by intravascular ultrasound study. Echocardiography revealed critical mitral stenosis, and left atrial clot with mild left ventricular dysfunction. Coagulation profile revealed sub-therapeutic international normalized ratio levels. The sequential angiographic images, normal intravascular ultrasound study, and presence of atrial fibrillation are confirmatory of coronary embolism as the cause of myocardial infarction. Anticoagulation and treatment of acute coronary syndrome were initiated and she was referred for closed mitral valvulotomy. CONCLUSIONS Coronary artery thromboembolism as a nonatherosclerotic cause of acute coronary syndrome is rare. The treatment consists of aggressive anticoagulation, antiplatelet therapy, and interventional options, including simple wiring when possible. In this context, primary prevention in the form of patient education on optimal anticoagulation with oral vitamin K antagonist and medical advice about imminent thromboembolic risks are of extreme importance.

  16. 华法林抗凝治疗对妊娠合并心脏瓣膜病患者的影响%Effect of warfarin anticoagulant therapy on pregnant women with valvular heart disease

    Institute of Scientific and Technical Information of China (English)

    刘燕; 刘红威

    2016-01-01

    Objective To investigate the effect of warfarin anticoagulant therapy on pregnant women with valvular heart disease and fetus.Methods Seventy-eight cases of pregnant women with valvular heart disease in our hospital from October 2014 to October 2005 were treated with anticoagulant therapy.Patients were randomly divided into group A and group B.Patients received full warfarin therapy in group A(n =44) and low molecular weight heparin and warfarin alternative therapy in group B (n =34).The pregnancy outcomes of two groups were compared.Results No severe complications of embolism were observed in the two groups of patients during pregnancy.There was no significant differences in terms of cardiac function changes,stillbirth,abortion,postpartum hemorrhage,neonatal asphyxia,neonatal malformations and low birth weight indicators between the two groups (P > 0.05).Conclusions Low-dose warfarin (less than 5 mg/d) is a safe and effective anticoagulant therapy for patients with valvular heart disease during pregnancy.%目的 探讨使用华法林抗凝治疗对合并心脏瓣膜病孕妇及胎儿的影响.方法 选择2005年10月至2014年10月78例合并心脏瓣膜病妊娠妇女进行抗凝治疗.随机分为A、B两组,A组44例患者全程采用口服国产华法林抗凝治疗,B组34例患者采用华法林与低分子肝素交替抗凝治疗.比较两组患者的妊娠结局.结果 两组妊娠期间均无严重栓塞并发症;两组患者妊娠强化心功能变化情况、死胎、流产、产后大出血、新生儿窒息、新生儿畸形、新生儿低体质量等指标比较差异也未见统计学意义(P均>0.05).结论 合并心脏瓣膜病的妇女在妊娠期间单一服用小剂量华法林(<5 mg/d)为一种相对安全有效的抗凝治疗.

  17. Impact of renal function on ischemic stroke and major bleeding rates in nonvalvular atrial fibrillation patients treated with warfarin or rivaroxaban: a retrospective cohort study using real-world evidence.

    Science.gov (United States)

    Weir, Matthew R; Berger, Jeffrey S; Ashton, Veronica; Laliberté, François; Brown, Kip; Lefebvre, Patrick; Schein, Jeffrey

    2017-10-01

    Renal dysfunction is associated with increased risk of cardiovascular disease and is an independent predictor of stroke and systemic embolism. Nonvalvular atrial fibrillation (NVAF) patients with renal dysfunction may face a particularly high risk of thromboembolism and bleeding. The current retrospective cohort study was designed to assess the impact of renal function on ischemic stroke and major bleeding rates in NVAF patients in the real-world setting (outside a clinical trial). Medical claims and Electronic Health Records were retrieved retrospectively from Optum's Integrated Claims-Clinical de-identified dataset from May 2011 to August 2014. Patients with NVAF treated with warfarin (2468) or rivaroxaban (1290) were selected. Each treatment cohort was stratified by baseline estimated creatinine clearance (eCrCl) levels. Confounding adjustments were made using inverse probability of treatment weights (IPTWs). Incidence rates and hazard ratios of ischemic stroke and major bleeding events were calculated for both cohorts. Overall, patients treated with rivaroxaban had an ischemic stroke incidence rate of 1.9 per 100 person-years (PY) while patients treated with warfarin had a rate of 4.2 per 100 PY (HR = 0.41 [0.21-0.80], p = .009). Rivaroxaban patients with an eCrCl below 50 mL/min (N = 229) had an ischemic stroke rate of 0.8 per 100 PY, while the rate for the warfarin cohort (N = 647) was 6.0 per 100 PY (HR = 0.09 [0.01-0.72], p = .02). For the other renal function levels (i.e. eCrCl 50-80 and ≥80 mL/min) HRs indicated no statistically significant differences in ischemic stroke risks. Bleeding events did not differ significantly between cohorts stratified by renal function. Ischemic stroke rates were significantly lower in the overall NVAF population for rivaroxaban vs. warfarin users, including patients with eCrCl below 50 mL/min. For all renal function groups, major bleeding risks were not statistically different between

  18. Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).

    Science.gov (United States)

    Steinberg, Benjamin A; Simon, DaJuanicia N; Thomas, Laine; Ansell, Jack; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Peterson, Eric D; Piccini, Jonathan P

    2017-05-15

    Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights

  19. Effect of encapsulation in the anion receptor pocket of sub-domain IIA of human serum albumin on the modulation of pKa of warfarin and structurally similar acidic guests: a possible implication on biological activity.

    Science.gov (United States)

    Datta, Shubhashis; Halder, Mintu

    2014-01-05

    Supramolecular and bio-supramolecular host assisted pKa shift of biologically relevant acidic guests, warfarin and coumarin 343, has been monitored using both steady-state and time resolved fluorescence spectroscopy. The anion receptors present in sub-domain IIA of human serum albumin (HSA) stabilize the anionic form of the guest and thereby shift pKa towards acidic range. On the other hand, the preferential binding of the neutral form of guests in the non-polar hydrophobic cavity of β-cyclodextrin results in up-shifted pKa. This shifting of pKa of drugs like warfarin, etc., whose therapeutic activity depends on the position of the acid-base equilibrium in human system, is of great importance in pharmacokinetics. The release of the active form of such drugs from macrocyclic carrier and subsequent distribution through the carrier protein should depend on the modulation of the overall pKa window brought about by the encapsulation in these hosts. Present work also suggests that properly optimized encapsulation in appropriate receptor pocket can enhance the bioavailability of drugs. This work also opens up the possibility to use HSA as encapsulator, instead of traditional cyclodextrins or other polymeric hosts, since such system may overcome toxicity as well as biocompatibility issues.

  20. Safety and efficacy of pharmacogenomics-guided warfarin dosing algorithms: a systematic review%基因导向的华法林给药模型安全性和有效性的系统评价

    Institute of Scientific and Technical Information of China (English)

    赵楠; 张亚同; 程刚; 邹梅娟; 胡欣

    2012-01-01

    目的:评价基因导向的华法林给药模型(pharmacogenomics-guided warfarin dosing algorithms)在华法林应用初期的安全性和有效性.方法:检索数据库,纳入随机对照试验(RCT),并评价其方法学质量,提取资料,用Revman 5.0软件进行Meta分析.结果:共纳入5篇文献,其方法学质量、研究人群等存在很大差异,可能存在较高的偏倚风险.Meta分析结果表明:华法林给药初期应用基因导向的华法林给药模型可以降低不良反应发生率[ RR=0.52,95% CI(0.28,0.97),P=0.04],但由于存在异质性,故进行亚组分析;在INR治疗范围内的时间[SMD=-0.35,95% CI(-0.51,-0.18),P<0.00001]、第一次达INR治疗范围的时间[SMD=-1.12, 95% CI(-1.36,-0.89),P<0.00001]、华法林初始剂量和稳定剂量的差值[SMD=-0.33,95% CI(-0.55,-0.11),P=0.003],PG组均要优于C组,且达到统计学意义.结论:给药初期,应用基因导向的华法林给药模型可以提高华法林给药的安全性和有效性.%Objective: To evaluate the safety and efficacy of pharmacogenomics-guided warfarin dosing algorithms in the initial stage of warfarin dosing. Methods; Randomized and controlled trials were collected from databases. Methodological quality of included studies was evaluated. Meta-analysis was conducted using Revman 5. 0 software. Results; A total of 5 RCTs were included. There were significant differences in terms of design quality, length of follow-up , intervention and outcome measures which may have biased the results. The result of Meta-analysis showed that the pharmacogenomics-based algorithms lowered the rates of adverse events[ RR =0. 52, 95% CI (0. 28 ,0. 97) ,P =0. 04] . However, owning to the heterogeneity, we had to conduct subgroup analysis. Additionally, pharmacogenomics-based algorithms significantly increased the percentage time INR in the therapeutic range [ SMD = -0.35 , 95% CI ( -0.51, -0.18), P <0.000 01 ] , decreased time to first therapeutic INR [ SMD

  1. Varfarina e femprocumona: experiência de um ambulatório de anticoagulação Warfarina y femprocumona: experiencia de una unidad de anticoagulación Warfarin and phenprocoumon: experience of an outpatient anticoagulation clinic

    Directory of Open Access Journals (Sweden)

    Tiago Luiz Luz Leiria

    2010-01-01

    Full Text Available FUNDAMENTO: Os anticoagulantes orais são amplamente utilizados na cardiologia. Contudo, uma avaliação sobre o seu uso na prática clínica ainda é necessária. OBJETIVOS: Descrever as diferenças na manutenção do controle da anticoagulação, bem como a incidência de eventos hemorrágicos e tromboembólicos entre os usuários de varfarina e femprocumona. MÉTODOS: Estudo de coorte não concorrente de 127 pacientes em uso de anticoagulação oral. RESULTADOS: A femprocumona foi o anticoagulante mais utilizado em 60% dos pacientes. A prevalência de INRFUNDAMENTO: Los anticoagulantes orales son ampliamente utilizados en la cardiología. Con todo, una evaluación acerca de su utilización en la práctica clínica es necesaria todavía. OBJETIVO: Describir las diferencias en el mantenimiento del control de la anticoagulación, así como la incidencia de eventos hemorrágicos y tromboembólicos entre sus usuarios de warfarina y femprocumona. MÉTODOS: Estudio de cohorte no concurrente de 127 pacientes en tratamiento con anticoagulación oral. RESULTADOS: La femprocumona fue el anticoagulante más utilizado en el 60% de los pacientes. La prevalencia de INRBACKGROUND: Oral anticoagulants are broadly used in cardiology. However, it is still necessary to evaluate their use in clinical practice. OBJECTIVES: To describe the differences in the maintenance of anticoagulation control, as well as the incidence of hemorrhagic and thromboembolic events among users of warfarin and phenprocoumon. METHODS: Non-concurrent cohort study of 127 patients using oral anticoagulation. RESULTS: Phenprocoumon was the most frequently used anticoagulant in 60% of the patients. The prevalence of RNI<2 at the last medical appointment was higher among warfarin users (46% vs. 19.5%; p<0.001. During the follow-up, Phenprocoumon users were within the therapeutic range during 60.7% of the period, in comparison with 45.6% of warfarin users (OR:1.84; 95%CI:1.59-2.13; P<0

  2. The overview of warfarin related gene mutation detection technologies%论华法林相关基因突变检测技术

    Institute of Scientific and Technical Information of China (English)

    孙雪; 况赟; 阳喜定; 郭成贤; 阳国平

    2015-01-01

    Warfarin is a kind of commonly prescribed oral anticoagulant for preventing thromboem-bolic disease. However, it is prone to cause thromboembolism or bleeding due to its narrow therapeutic window. The predominant polymorphisms in CYP2C9 and VKORC1 genes, encoding for metabolizing enzyme cy-tochrome P450 2C9 (CYP2C9) and target enzyme vitamin K epoxide reductase complex subunit 1 (VKORC1), have significant impact on individual differences in dose requirement. So the detection of CYP2C9 and VKO-RC1 mutation has important reference value to individualized therapy. At present, the usually detection methods of CYP2C9 and VKORC1 include PCR-RFLP, TaqMan, pyrosequencing, HRM, POCT, melting curve analysis, MS, DHPLC,and so on. The characteristics of these detection methods will be compared in this article to find out the most suitable technical detection methods for clinical application and promotion.%华法林为一种常用的口服抗凝药,主要用于治疗血栓栓塞性疾病。但其治疗窗窄、个体差异大,容易引起血栓或出血的风险。代谢酶CYP2C9和作用靶点VKORC1基因多态性对华法林个体剂量差异有显著影响,因此CYP2C9和VKORC1基因突变的检测对于华法林的个体化治疗具有重要的参考价值。目前用于 CYP2C9和 VKORC1突变检测的方法有 PCR-RFLP、TaqMan、pyrosequencing、HRM、POCT、熔解曲线分析技术、MS、DHPLC等。本文将对这些检测方法的特点进行比较分析,以发现适合临床应用推广的技术检测方法。

  3. 服用华法林而致咯血患者的药学监护%Pharmaceutical Care on Patients With warfarin Causing Hemoptysis

    Institute of Scientific and Technical Information of China (English)

    刘强; 谢丽君; 陈宜锋

    2015-01-01

    Objective To explore the pharmaceutical care points and standardized pharmacy practice models for the adverse re-action events using warfarin by clinical pharmacists. Methods Clinical pharmacists assisted clinicians to find the cause which led pa-tients to bleed, individualized treatment plans and pharmaceutical care measures were also proposed. Results Clinical pharmacists could provide appropriate intervention by means of monitor the international normalized ratio ( INR) values and analyze the drug inter-actions. Patients were cured and discharged after therapy. Conclusion Clinical pharmacist must participate in clinical practice ener-getically, provide standardized pharmaceutical care for patients, and guarantee the use of drug safe, effective and reasonable.%目的:探讨服用华法林导致出血不良事件的药学监护内容以及临床药师参与药物治疗的模式。方法对服用华法林而致出血的病例,临床药师协助临床医师寻找出血原因,并对其治疗全过程进行监护。结果经药师仔细询问该患者用药史建立用药与INR时间表后,判断出血受药物相互不良作用影响较大,并进行治疗药物优化建议和密切监护出血情况后,患者康复出院。结论临床药师积极参与临床实践,作为药物治疗团队中的一员,可利用药学特长协助临床医师做出药物相关性疾病的诊断,共同监护药物治疗的有效性、安全性和依从性,体现了临床药师价值。

  4. The cliniacl observation on the influence of combined u se of allopurinol and warfarin on the INR of chronic permanent AF hyperuricemia patients%别嘌醇与华法林联合使用对慢性永久性房颤合并高尿酸血症患者INR的影响

    Institute of Scientific and Technical Information of China (English)

    杨海见; 李维郑; 于树安; 尹林凤

    2016-01-01

    Absrtact: Object vie To observe the INR of AF hyperuricemia patients 'prothrombin time under the situation where both allopurinol and warfarin are used to the treatment of anticoagulation . Methods A total of 240 patients with chronic permanent AF hyperuricemia were collected and then divided randomly into two groups:warfarin treatment group(120 cases), to maintain the original dose warfarin therapy and keep a low-purine diet;and the combined treatment group (120 cases), also in the conventional warfarin antithrombotic therapy and a low-purine diet, on this basis, plus allopurinol 100 mg, three times a day, which last for two weeks .Then observing and examining the change of the two group's INR after the treat-ment. Results The INR of the combined treatment group was obviously higher than the warfarin group ( P<0 .05 ) . Conclusion Allopurinol can increase antithrombotic effect of warfarin .INR should be monitored regularly during the treatment so as to adjust warfarin dosage accordingly .%目的:观察别嘌醇对应用华法林抗凝治疗的房颤合并高尿酸血症患者凝血酶原时间的国际标准化比值( INR)的影响。方法收集华法林抗栓治疗的慢性永久性房颤合并高尿酸血症患者240例,随机分为两组。华法林治疗组(120例)维持原剂量华法林抗凝治疗,嘱低嘌呤饮食;联合治疗组(120例)在常规华法林抗栓治疗,低嘌呤饮食的基础上,加用别嘌醇100 mg,每日3次口服。治疗2周后,观察并检测两组患者治疗前后INR的变化。结果联合治疗组的INR较华法林治疗组明显增高(P<0.05)。结论别嘌醇会增加华法林的抗栓作用,治疗过程中应定期监测INR,及时调整华法林用量。

  5. Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

    Directory of Open Access Journals (Sweden)

    Yoleima Lozada

    2012-04-01

    Full Text Available La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR; cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K, preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral o placebo. El punto final primario, INR Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR; when safety range is exceeded, Vitamin K (Vit-K could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR, of 50% (CI95%: 14.4-85.6 ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9. No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

  6. Reversal of Warfarin Era Thinking.

    Science.gov (United States)

    Shatzel, Joseph J; Daughety, Molly M; Prasad, Vinay; DeLoughery, Thomas G

    2017-10-05

    Anticoagulation offers benefits in appropriately selected patients, however, all anticoagulants increase the risk of bleeding, which can be, at times, life threatening. For decades, vitamin K antagonists were the only oral anticoagulants available to physicians and their patients. In recent years, we have witnessed the approval of five direct oral anticoagulants (DOACs), which have shifted prior paradigms in anticoagulation such as omitting the need for routine therapeutic monitoring and lessening concerns about food and drug interactions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Vitamina K: metabolismo, fontes e interação com o anticoagulante varfarina Vitamin K: metabolism, sources and interaction with the anticoagulant warfarin

    Directory of Open Access Journals (Sweden)

    Karin Klack

    2006-12-01

    phylloquinone. Dark green leafy vegetables, usually mixed with oils, nuts and some fruits, including kiwi, avocado, grapes, plums, and figs are rich sources of vitamin K, whereas cereals, grains, breads, and dairy products present low amounts. The daily ingestion of approximately 1µg/kg body-weight is considered safe, even with concomitant oral anticoagulant use, since stable vitamin concentration contributes to anticoagulant efficacy. The most commonly used oral anticoagulant formation is warfarin, that is indicated to both prophylactic and therapeutic tromboembolic phenomena. It is currently monitored by assessing prothrombin time, after adjusting for the international normalized ratio (INR. Usually, the oral dose is adjusted to set the INR in the range of 2 - 3, in order to achieve the treatment objective. The anticoagulating efficacy is influenced by a variety of clinical factors, such as weight gain, diarrhoea, vomiting, age under 40, and excessive vitamin K daily consumption.

  8. 华法林引发骨质疏松症的发病机制及治疗策略%Pathological mechanism and therapeutic strategy of warfarin-related osteoporosis

    Institute of Scientific and Technical Information of China (English)

    赵斐; 张一娜

    2016-01-01

    Osteoporosis is a systemic bone metabolism disorder characterized by reduced bone mineral content , damaged bone microstructure and compromised bone strength that may predispose to an increased risk of fracture and an increased bone fragility . Warfarin, a vitamin K antagonist , can inhibit carboxylation of osteocalcin , reduce bone calcium deposition , and thus interact with bone metabolism and induce osteoporosis or bone fracture , especially in the elderly patients .The osteoporosis risk related with the use of warfarin may be associated with dosage and time of duration .The basic principle to prevent drug-induced osteoporosis is the same as that for primary osteoporosis .Calcium and vitamin D should be used for prevention .Bisphosphonates , calcitonin, estrogens and parathyroid hormone analogues can be selected for the treatment of osteoporosis or fracture induced by warfarin according to the individual condition of patients .In this paper , we reviewed the advances on pathological mechanism , research progress and therapeutic strategy of osteoporosis induced by warfarin .%骨质疏松症是一种以骨矿物质含量低下、骨微结构损坏、骨强度降低、骨脆性增加、易发生骨折为主要特征的全身性骨代谢障碍性疾病。华法林可拮抗维生素K,使骨钙素的羧化受抑制,减少骨钙沉积,抑制骨矿化,从而干扰骨代谢,导致骨质疏松症或骨折,对于老年患者的影响尤其明显。长期服用华法林导致骨质疏松症的风险可能与用药剂量和时间相关。目前预防和治疗华法林引起的骨质疏松症主要依据原发性骨质疏松症的治疗原则,对于长期服用华法林的患者应补充钙剂和维生素D以预防骨质疏松症,对于已出现骨质疏松症的患者根据具体病情选择用双膦酸盐、降钙素、雌激素和甲状旁腺类似物治疗。本文对华法林引发骨质疏松症的发病机制、研究进展和治疗策略进行综述。

  9. Perioperative management of patients with traumatic intracranial hemorrhage and pretraumatic oral warfarin%口服华法令合并外伤性颅内出血患者的围手术期处理

    Institute of Scientific and Technical Information of China (English)

    陈开来; 鲁晓杰; 季卫阳

    2011-01-01

    Objective To study the perioperative management in the treatment of traumatic intracranial hemorrhage in patients with pretraumatic anticoagulation therapy of oral warfarin. Method 10 patients of traumatic intracranial hemorrhage with pretraumatic anticoagulation therapy of oral warfarin received vitamin K, FFP and PCC treatment to reverse the anticoagulation condition after admission. 9 patients underwent the operation for evacuation of intracranial hematoma. Low - molecular - weight heparin was administered as prophylactic dose in 3 patients. Results All patients in this group were survival. 5 of them get well recovery. 3 of them remained different degrees of hemiplegia or aphasia and 2 patient got vegetative state after operation. Conclusions Pre - operative normalization of coagulation capacity is of utmost importance in patients with head injury and plays an important role in the prognosis of patients.%目的 探讨长期口服抗凝药物华法令合并外伤性颅内出血患者的围手术期处理措施.方法 10例此类患者入院后给予维生素K、新鲜冰冻血浆和凝血酶原复合物来逆转患者的抗凝状态.9例患者接受开颅手术清除颅内血肿.3例患者术后接受预防剂量的低分子肝素的治疗.结果 术后所有患者均存活,其中5例恢复良好,3例遗留不同程度的偏瘫或失语症状,2例患者术后长期植物状态生存.结论 伤后、术前迅速纠正凝血指标参数至关重要,与患者预后密切相关.

  10. Hematoma de músculo iliopsoas na vigência de tratamento com varfarina Hematoma de músculo iliopsoas en la vigencia de tratamiento con warfarina Iliopsoas muscle hematoma during treatment with warfarin

    Directory of Open Access Journals (Sweden)

    Gabriel Zago

    2010-01-01

    Full Text Available A varfarina é droga amplamente utilizada na prevenção de fenômenos tromboembólicos e o conhecimento de seus efeitos adversos faz-se necessário para o acompanhamento dos pacientes. Embora o desenvolvimento de discrasias sanguíneas seja complicação potencial nesses pacientes, a ocorrência de sangramento retroperitoneal é rara. Este artigo discute o caso de um paciente que evoluiu com hematoma do músculo iliopsoas durante tratamento com a referida droga, pós-implante de prótese aórtica metálica, com quadro clínico envolvendo importantes diagnósticos diferenciais.La warfarina es un fármaco ampliamente utilizado en la prevención de fenómenos tromboembólicos, y el conocimiento de sus efectos adversos se hace necesario para el seguimiento de los pacientes. Aunque el desarrollo de discrasias sanguíneas es la complicación potencial en estos pacientes, la ocurrencia de sangrado retroperitoneal es rara. Este artículo discute el caso de un paciente que evolucionó con hematoma del músculo ileopsoas durante tratamiento con el referido fármaco en el postimplante de prótesis mitral metálica, con cuadro clínico implicando importantes diagnósticos diferenciales.Warfarin is a widely used drug for the prevention of thromboembolic events. Knowledge of its adverse effects is necessary for patient follow-up. Although the development of blood dyscrasias is a potential complication in these patients, retroperitoneal bleeding is rare. This article reports the case of a patient who developed iliopsoas muscle hematoma during treatment with warfarin after implantation of a metallic prosthetic aortic valve. The clinical manifestations involved important differential diagnoses.

  11. Comparison between Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma (FFP) for the Urgent Reversal of Warfarin in Patients with Mechanical Heart Valves in a Tertiary Care Cardiac Center.

    Science.gov (United States)

    Fariborz Farsad, Bahram; Golpira, Reza; Najafi, Hamideh; Totonchi, Ziae; Salajegheh, Shirin; Bakhshandeh, Hooman; Hashemian, Farshad

    2015-01-01

    Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 mL/Kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained at different time after PCC and FFP infusion. The mean ± SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.

  12. 心脏机械瓣膜置换术后华法林低强度抗凝疗效观察%Efficacy of warfarin low intense anticoagulation after heart valve replacement

    Institute of Scientific and Technical Information of China (English)

    刘状; 葛圣林; 张成鑫

    2014-01-01

    目的:探讨安徽地区汉族人心脏机械瓣膜置换术后华法林低强度抗凝应用于患者的安全性,为瓣膜置换术后患者给予最佳的华法林抗凝剂量及最佳的INR控制标准提供参考。方法对安徽医科大学第一附属医院2010年1月至2013年1月期间509例安徽省地区汉族人群人工机械瓣膜置换术后的患者给予华法林低强度抗凝治疗。随访期间,记录其PT、INR值及华法林剂量。统计出血及血栓、栓塞等不良事件的发生。结果失访及数据不完整的有40例,数据较完整的有469例,随访1~37个月,平均(18.13±6.02)月,总随访1960.8人年。男211例,女258例,平均年龄(40.52±13.38)岁,其中行MVR 268例,AVR 115例,DVR 86例。所换瓣膜均为双叶机械瓣膜,其中153枚St.Jude Regent瓣膜,291枚CarboMedics瓣膜,111枚国产GKS瓣膜。结果平均INR为2.11±0.56,平均华法林剂量为(3.124±2.4)mg。共有47例抗凝相关并发症,其中出血事件37例(发生率为1.89%pt-y),血栓、栓塞事件有10例(发生率为0.51%pt-y)。另外,5例死亡,与抗凝相关有3例。术前患者共有316例合并房颤,43例合并左房血栓。结论安徽省人群瓣膜置换术后患者INR控制在1.8~2.2是合适的,可以有效控制血栓、栓塞及出血等并发症的发生。合并房颤患者及行DVR的患者的抗凝相关并发症发生率较高,此类患者应加大复查频次,及时调整华法林剂量。%Objective To evaluate the safety of warfarin low intensity anticoagulation after mechanical heart valve replacement in Anhui Han population ,and to identify optimum international normalized ratio ( INR) levels and required warfarin doses and anticoagulation-re-lated complications in patients following mechanical heart valve replacement .Methods We studied 509 patients who underwent me-chanical valve replacement with low intensity

  13. Quality Evaluation of Anticoagulant Therapy in Patients Who Taking Warfarin in Our Hospital%我院服用华法林患者抗凝治疗质量评价

    Institute of Scientific and Technical Information of China (English)

    李玲玲; 李莹; 都丽萍; 李雯; 梅丹

    2016-01-01

    目的:评价服用华法林患者的抗凝治疗质量,为加强服用华法林患者的管理提供数据支持。方法:回顾性分析符合纳入标准的214例服用华法林患者的相关临床资料。结果:所有患者服用华法林的平均时间为(321.64±189.50)d,非住院期间于我院检测国际标准化比值(INR)的平均次数为(12.01±7.03)次;抗凝治疗期间INR<2.0的占51.96%,2.0≤INR≤3.0的占39.13%, INR>3.0的占8.91%;INR目标值≤2.0的占45.33%,INR目标值=2.5的占38.32%,INR目标值≥3.0的占0.93%;平均目标范围内的时间百分比(TTR)为(50.80±22.32)%;不同年龄及不同疾病患者的TTR比较,差异均无统计学意义(P>0.05)。结论:部分服用华法林患者抗凝治疗质量较差,需加强抗凝治疗质量的管理,使抗凝安全、有效。%OBJECTIVE:To evaluate the quality of anticoagulant therapy in patients who took warfarin and provide data sup-porting for strengthening the management of these patients. METHODS:A retrospective analysis of related clinical data of 214 pa-tients who meet the inclusion criteria was performed. RESULTS:The average time for patients took warfarin was (321.64 ± 189.50)d,average times for tested INR was(12.01±7.03)times in clinic;when anticoagulant therapy,INR3.0 accounted for 8.91%;patients with target INR≤2.0 accounted for 45.33%,target INR=2.5 accounted for 38.32%,and target INR≥3.0 accounted for 0.93%;the average TTR was (50.80 ± 22.32)%;and there was no statistical significance in the TTR of different ages and diseases(P>0.05). CONCLUSIONS:The anti-coagulant therapy in some patients who took warfarin shows poor quality,it needs strengthening the quality management to make it safe and effective.

  14. Fibrilação atrial crônica, AVC e anticoagulação: sub-uso de warfarina ? Atrial fibrillation, stroke and anticoagulation: under-use of warfarin?

    Directory of Open Access Journals (Sweden)

    Norberto L. Cabral

    2004-12-01

    Full Text Available OBJETIVO: Correlacionar acidente vascular cerebral (AVC cardioembólico em portadores de fibrilação atrial (FA crônica não valvular, potencialmente evitáveis, previamente acompanhados por cardiologistas, sem restrições ao uso da warfarina, com o grau de absorção das recomendações e limitações publicadas sobre anticoagulação e FA. MÉTODO: Registramos prospectivamente todos os casos de AVC internados em dois hospitais de Joinville.Na presença de FA, foi questionado aos pacientes se sabiam da existência da arritmia, freqüência de visitas a cardiologistas e uso prévio de warfarina. Posteriormente aplicamos um questionário transversal a 11 cardiologistas sobre o FA, anticoagulação e AVC. RESULTADOS: Entre 167 pacientes com AVC, 22 tinham FA prévia e AVC isquêmico. Destes, 15 tinham consultado previamente um cardiologista. Nove pacientes faleceram, sete tiveram alta anticoagulados e seis não receberam warfarina. O questionário evidenciou que 91% dos colegas conheciam as recomendações publicadas, mas somente 54 % deles consideravam-nas aplicáveis para pacientes do serviço público. CONCLUSÃO: A anticoagulação na FA reduz 68% o risco relativo para AVC/ano. Logo, 11 dos 22 pacientes poderiam ter evitado o evento. Extrapolando a incidência em 1997 e a população atual, podemos considerar que 4% de todos os AVC por ano em Joinville são potencialmente evitáveis.OBJECTIVE: To correlate the presence of non valvar atrial fibrillation (NVAF and cardioembolic stroke in patients previously assisted by cardiologists and without restrictions to the use of warfarin, with the level of acceptance of the recommendations published about chronic AF among these professionals. METHOD: All strokes accepted in two hospitals of Joinville were prospectively recorded. The patients with AF were questioned about their previous knowledge about arrythmia, the frequency they had seen their cardiologists and the use of warfarin. Later, 11

  15. The anti-thrombus effect of Warfarin on the patients with paroxysmal atrial fibrillation and its nursing%华法林对阵发性心房颤动的抗血栓作用与护理

    Institute of Scientific and Technical Information of China (English)

    陆敏智; 陈新军; 张华

    2008-01-01

    目的 探讨不同抗凝强度的华法林对阵发性非瓣膜病性房颤(PAF)患者预防血栓作用及护理对策.方法 选取中高危PAF病例826例,分别使用不同剂量的华法林进行抗凝治疗,随访心脑血管疾病发生情况,比较主要终点、次要终点事件发生率及主要出血事件及次要出血事件发生率,分析血栓栓塞和出血事件发生率与国际标准化凝血酶原时间比值(INR)的相关性,比较健康教育在预防不良事件发生中的作用.结果 对中高危PAF患者,INR在1.8~3.0较INR在1.4~1.7主要终点、次要终点事件发生率低(P<0.05),而出血事件无增加(P<0.05).结论 加强健康教育及监测,及时观察可降低不良事件发生.对PAF患者,针对性地指导患者合理饮食、用药,预防及观察副作用,提高患者的依从性,建立完整的社区服务体系,可以使华法林得到更安全、有效的应用.%Objective To explore the anti-thrombus effect of Warfarin on the patients with paroxysmal atrial fibrillation (PAF)and its nursing.Methods 826 medium and high risk cases with PAF were selected and were treated with different dosages of Warfarin,their incidency of cerebrovaseular disease were followed,the occurrence of main and secondary events and bleeding at the end of following were compared,the realationship between the incidence of thromboembolism and bleeding and international normalized ratio(INR) of pro-time prothrombin time were analyzed.and the effects of health education in preventing the adverse events were also compared.Results Among those cases,the incidence of main and secondary events at the end of following showed lower with the INR of 1.8~3.0 than those of 1.4~1.7.while the occurance of bleeding did not increase.Conclusions It is effective and safe to apply Warfarin by follwing measures:enforcing health education and monitoring,observating the adverse events timely,informing PAF patients with the knowledge on diet

  16. Application of solution-focused nursing approach in warfarin therapy for atrial fibrillation patients%聚焦解决护理模式在房颤患者华法林治疗管理健康教育中的应用

    Institute of Scientific and Technical Information of China (English)

    于金美; 卢万俊; 陈爱妹; 蒋燕; 张敏; 仲伯琴; 颜庆月; 黄婧

    2016-01-01

    目的:探讨聚焦解决护理模式在房颤患者华法林治疗管理健康教育中的应用。方法对100例住院房颤患者的服药依从性、监测国际标准化比值依从性、国际标准化比值达标率、并发症情况及再次栓塞事件发生率进行比较分析。结果健康教育后研究组患者心房颤动华法林抗凝自我护理知识知晓率及华法林抗凝同意率显著高于对照组(P<0.05),心房颤动抗凝管理量表知晓率显著高于对照组(P<0.01),服药依从性、监测国际标准化比值依从性、国际标准化比值达标率均显著优于对照组(P<0.01),出血并发症及再次栓塞事件均显著少于对照组(P<0.05或0.01)。结论聚焦解决护理模式可有效提高房颤患者华法林抗凝自我管理能力,提高治疗依从性。%Objective To explore the application of solution‐focused nursing approach (SFNA) in warfarin therapy for atrial fibrillation (AF) patients .Methods Drug compliance ,international normalized ratio (INR) compliance ,INR standardized rate ,complications and the incidence of re‐embolism events were compared in 100 hospitalized AF patients .Results After health education understanding rate of self‐care knowledge of AF warfarin anticoagulation and consent rate to warfarin anticoagulation (P<0 .05) and the understanding rate of AF warfarin anticoagulation management scale (P<0 .01) were significantly higher , drug compliance ,INR compliance and INR standardized rate better (P<0 .01) ,and complications and re‐embolism events fewer (P<0 .05 or 0 .01) in research than in control group .Conclusion The SFNA ap‐plied in health education to AF patients undergoing warfarin therapy could effectively improve their self‐management abilities and treatment compliance .

  17. Hematoma of the rectus abdominis caused by the application of warfarin sodium and other medicine%华法林钠与多药联用致腹直肌内血肿

    Institute of Scientific and Technical Information of China (English)

    冉明月; 毛敏; 李春岩; 黄力

    2015-01-01

    1例80岁男性高血压病、动脉粥样硬化、风湿性心脏病、心房颤动患者长期口服华法林钠(3 mg,1次/d),国际标准化比值(INR)维持在2.00 ~3.00.因肺部感染伴发热加用哌拉西林钠他唑巴坦钠(4.5g,1次/8 h)静脉滴注、复方氨林巴比妥(2 ml)肌内注射、洛索洛芬钠(30 mg)口服等.加药前凝血酶原时间(PT) 27 s,INR 2.45.2d后,患者出现痰中带血.次日停用华法林钠.停用华法林钠第2天,患者突发左上腹剧烈胀痛并可触及包块,触痛明显,当日PT42 s,INR 4.46.次日腹部超声检查示左侧腹直肌内有4.5 cm ×2.7 cm×1.5 cm囊性结构,腹部CT检查见左侧腹直肌内圆形高密度影,考虑左侧腹直肌内血肿可能性大.立即给予维生素K110 mg,1次/d肌内注射,停用哌拉西林钠他唑巴坦钠,换为头孢他啶.2d后,患者腹痛基本消失,PT16s,INR 1.11.1周后恢复口服华法林钠(起始量2.25 mg,1次/d),并根据INR调整剂量.1个月后腹部超声复查示血肿明显减小(3.5 cm ×0.8 cm).%An 80-year-old male patient with hypertension, arteriosclerosis, rheumatic heart disease, and atrial fibrillation long-term daily oral warfarin sodium 3 mg once daily.International normalized ratio (INR) was maintained at 2.00 to 3.00.An intravenous infusion of piperacillin sodium and tazobactam sodium 4.5 g every 8 hours, intramuscular injection of compound aminophenazone and barbital 2 ml, oral loxoprofen sodium 30 mg and other drugs were added to his regimen for pulmonary infection and high fever.Before the drug combination, prothrombin time (PT) was 27 s, and the INR was 2.45.Two days later, the patient developed hemoptysis.The next day, warfarin sodium was stopped.On the second day of discontinuation of warfarin sodium ,the patient suddenly felt a severe pain in the left upper abdomen with the sign of palpable mass and tenderness.Meanwhile, the PT was 42 s, and the INR was 4.46.On the next day, abdominal ultrasound examination showed that there

  18. Warfarin for improvement the cuffed central venous catheter dysfunction and clinical analysis%华法令对于带涤纶套中央静脉导管功能不良的改善及临床分析

    Institute of Scientific and Technical Information of China (English)

    汤小芳; 严连喜; 李康峰; 石平; 王成双; 孔若曦; 严宁; 周玉坤

    2016-01-01

    目的 观察口服华法令对于因血栓及纤维蛋白鞘而至涤纶套中央静脉导管置入后功能不良的改善并行临床分析.方法 59例带卡夫隧道导管患者,分为A组(28例)口服华法令1.5~3mg/d抗凝,对照组B组(31例)口服阿司匹林100mg/d抗凝,两组常规普通肝素封管.记录导管透析中血流量、回血静脉压,记录透析前后尿素氮、肌酐、超滤等,计算透析尿素清除指数,评估透析效果,定期检测非透析状态下国际标准化比值.比较导管留存时间、导管中位留存时间,并观察两组出血、导管相关性血流感染等并发症.观察一年时间.结果 A、B两组透析前后肌酐、尿素氮水平变化存在统计学差异,A组尿素清除指数均达标,A、B两组透析中血流量、回血静脉压比较存在统计学差异.A、B两组透析后比较肌酐、尿素氮水平、尿素清除指数以及国际标准化比值也存在统计学差异,且两组导管留存时间亦存在统计学差异.A组国际标准化比值维持在(2.00±0.93)之间,A、B两组未见出血、导管相关性血流感染并发症.结论 带卡夫中央静脉导管置后常规口服中等剂量华法令抗凝配合肝素封管较口服阿司匹林更能改善因血栓及纤维蛋白鞘而至导管功能不良,延长导管留存时间,且并发症少.但本研究样本量偏少,观察时间偏短,仍需进一步临床验证以证实口服华法令在带卡夫隧道导管置入后临床安全性及有效性.%Objectives To observe the improvement of warfarin for cuffed central venous catheter dysfunction due to thrombus and fibrin sheath and to carry on the clinical analysis.Methods 59 patients with cuffed central venous catheter were divided into group A (28 cases) and control group B (31 cases),patients in the group A were given warfarin 1.5 ~3mg/d,and patients in the control group B were given aspirin 100mg/d.The heparin was used to sealed tube in two groups.Catheter hemodialysis

  19. POR基因多态性与华法林维持剂量关系的研究%Associations of POR polymorphisms and warfarin stable maintenance dose in Han Chinese patients

    Institute of Scientific and Technical Information of China (English)

    胡蓉; 许哲; 赵立子; 李嘉丽; 王雪丁; 郑绮姗; 张希; 黄民

    2014-01-01

    Aim To explore the effect of genetic poly-morphisms of POR on the stable warfarin maintenance doses in Han Chinese patients receiving mechanical heart valve replacement. Methods The association between POR gene polymorphisms and warfarin doses of 185 Han Chinese patients were investigated through ANOVA or t test. SNPs of POR and VKORC1 were de-tected by Sequenom® DNA MassArray genotyping method. CYP2C9*3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP ) . Patients ’ clinical characteris-tics, INR value and daily dose were obtained from their medical records. Statistical analysis was performed by SPSS 21. 0 software. Results No mutant carriers of POR rs17148944 , POR rs56256515 and rs72553971 were found in this study. The genotype frequencies of other SNPs were in accordance with Hardy-Weinberg e-quilibrium. In the group of patients with CYP2C9*1*1 , the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(3. 50 ± 1. 07) mg·d-1 vs (3. 14 ± 0. 94) mg· d-1,P =0. 03. Also, in the group of patients with CYP2 C9*1*1 and VKORC1 rs9934438 G allele carri-ers, the mutant type carriers ( T carriers ) of POR rs17685 had a significantly higher dose than CC carri-ers(4. 76 ± 0. 90) mg·d-1 vs (4. 08 ± 1. 03) mg· d-1 ,P=0. 04. No significant difference was found in different genotypes of POR rs2868177 . Conclusion These results illustrate that POR rs17685 T carrier is closely associated with a higher warfarin maintenance dose, suggesting that this SNP is useful for clinical guidance of warfarin.%目的探讨POR基因多态性与华法林维持剂量的相关性。方法共纳入185例中国汉族人工心脏机械瓣膜置换术患者,采用 Sequenom MassARRAY® System 检测VKORC1及 POR 相关 SNPs,采用 PCR-RFLP 法检测CYP2C9*3基因型。采用 ANOVA 或 t检验考察目的 SNPs与患者华法林维持剂量的关系。结果在CYP2C9*1*1携带者中,POR rs17685

  20. 汉族人心脏瓣膜置换术后华法林用药剂量与基因型关系的相关性研究%Correlation of Warfarin Dosage and Genetic Polymorphism of Han-patients after Heart Valve Replacement

    Institute of Scientific and Technical Information of China (English)

    王玉庆; 董力; 石应康; 侯江龙; 江虹; 付博

    2016-01-01

    目的 探讨汉族人心脏瓣膜置换术后抗凝治疗华法林用药剂量个体差异与其基因多态性的相关性,预测患者华法林抗凝治疗的合理用药剂量,实现抗凝监测的个体化管理.方法 选择《中国人心脏瓣膜置换术后抗凝治疗数据库》中2011年1月1日至2012年12月31日在四川大学华西医院接受心脏瓣膜置换术、术后服用华法林行抗凝治疗,并接受国际标准化比值(international normalized ratio,INR)行抗凝监测的患者103例.其中男32例、女71例,年龄21~85 (48.64 ±11.66)岁,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法和基因测序技术检测CYP2C9 (rs1057910)和VKORC1 (rs9923231)基因位点的基因型和等位基因频率.用超高效液相色谱法(HPLC)检测患者华法林血药浓度,并用Sysmex CA7000 analyser试剂盒检测其凝血因子Ⅱ、Ⅶ、Ⅸ、Ⅹ活性.结果 性别、体表面积和凝血因子活性对华法林用药剂量的影响相对较弱.CYP2C9*3、VKORCI-1639、华法林血药浓度以及年龄对华法林用药剂量的影响相对较强,其影响程度(r2)依次为1.2%、26.5%、43.4%和5.0%.并由此推导出回归方程:Y=1.963-0.986× (CYP2C9*3)+ 0.893× (VKORC1-1639)+ 0.002×(华法林血药浓度)-0.019×(年龄).结论 结合CYP2C9和VKORC1两种基因的多态性检测结果、华法林血药浓度、年龄等非遗传因素建立的多元回归方程,可预测患者华法林抗凝治疗的合理用药剂量,从而实现抗凝监测的个体化管理,减少其并发症的发生.%Objectives To investigate the correlation of warfarin dose genetic and polymorphism of Han-patients after heart valve replacement,to forecast the anticoagulation therapy with warfarin reasonable dosage,and to realize individualized management of anticoagulation monitoring.Methods We selected 103 patients between January 1,2011 and December 31,2012 in West China Hospital of Sichuan University who were treated by oral

  1. Determination of Warfarin and Its Metabolite in Human Plasma by Ultra Performance Liquid Chromatog-raphy Tandem Quadrupole Mass Spectrometry (UPLC-MS/MS)%超高效液相串联质谱法检测人血浆中华法林及其代谢产物的浓度

    Institute of Scientific and Technical Information of China (English)

    邹晓华; 王双虎; 周云芳

    2015-01-01

    Objective:To establish an ultra performance liquid chromatography-tandem quadrupole mass spectrometry method for the determination of warfarin and its metabolite 7-hydroxywarfarin in human plasma. Methods: An ACQUITY UPLC® BEH C18 (50 mm × 2. 1 mm, 1. 7 μm) column was used as the stationary phase at 40℃. The mobile phase consisted of acetonitrile and water (con-taining 0. 1% formic acid) with gradient elution at a flow rate of 0. 4 ml·min-1 . Warfarin-d5 was used as the internal standard. The analytes were detected on a triple-quadrupole mass spectrometer equipped with an ESI interface in a positive mode. Results:The reten-tion time of warfarin and 7-hydroxywarfarin was 1. 8 min and 1. 5 min, respectively. Excellent linear calibration curve of warfarin and 7-hydroxywarfarin was obtained within the concentration range of 25-2 000 ng · ml-1 ( r =0. 999 3 ) and 5-500 ng · ml-1 ( r =0. 999 6), respectively. The lower limit of quantification of warfarin and 7-hydroxywarfarin was 5 ng·ml-1 and 2. 5 ng·ml-1 with the average recovery of 96. 9%-105. 3% and 97. 1% -103. 3%, respectively. The intra-and inter-day standard deviations were both less than 10%. Conclusion: The method is accurate and simple, and suitable for the determination of warfarin and its metabolite 7-hydroxywarfarin in human plasma.%目的::建立快速检测人血浆中华法林及其代谢产物7-羟基华法林浓度的UPLC-MS/MS方法。方法:用乙腈沉淀血浆蛋白的方法处理,运用Waters XEVO TQD三重四级杆液质联用仪,色谱柱为ACQUITY UPLC® BEH C18柱(50 mm ×2.1 mm,1.7μm);流动相为乙腈-水(含0.1%甲酸),梯度洗脱,流速为0.4 ml·min-1,柱温为40℃,内标为华法林-d5;质谱条件:电喷雾离子化源(ESI),正离子检测模式。结果:华法林和代谢产物7-羟基华法林的保留时间分别为1.8 min和1.5 min,线性范围分别为25~2000 ng·ml-1(r=0.9993)和5~500 ng· ml-1(r=0.9996),最低定量限分别为5,2.5 ng·ml-1,

  2. Evaluation of Subdivision of Warfarin Sodium Tablets Splitting for Different Equal Parts and by Different Methods%华法林钠片不同等份及不同方法分剂量的比较

    Institute of Scientific and Technical Information of China (English)

    刘元江

    2011-01-01

    Objective: To compared difference of various equal parts and various methods splitting warfarin sodium tablets. Method: Tablet cutters, scissors and knives were utilized to divide whole tablet produced by manufacture A, B and C into half and quarter parts. For one third and one fifth parts, the method scissor and pulverizing was applied to compare real weight and RSD of equal parts. Accuracy of subdivision of tablets of European Pharmacopiea was adopted. Results: RSDI/4 was more than RSDI/2 for three methods. When divided into half, all passed European Pharmacopeia standard except manufacture B used by knife while when divided into quarter all failed the requirement. For RSDI/5, all could not reach the requirement except manufacture B used by knife. For RSD1/3, the value was near to or beyond 15%. The real weight was not important difference for various operator when subdivided into two, three or five parts ( P〉0.05 ) . Conclusion: It was not accurate and rational to divide warfarin sodium tablets into such equal parts with abovementioned methods.%目的:比较华法林钠片不同等份及不同方法分剂量的差异。方法:分剂量成1/2、1/4片时采用切药器、剪刀、小刀,分剂量成1/3、1/5片时采用剪刀、磨粉分包,比较等份片实际重量的RSD及实际重量的差异,采用《欧洲药典》片剂分剂量准确性标准。结果:同一厂家华法林钠片3种方法分剂量,等份片RSD1/4均大于RSD1/2。分成二等份时,除国产B用小刀分剂量外,3厂家不同方法分剂量均符合《欧洲药典》标准。分成四等份时,3厂家不同方法分剂量均不符合《欧洲药典》标准。除国产B学生乙剪刀分剂量外,3厂家剪刀、磨粉分剂量成五等份时RSD均〉15%。三等份时RSD均接近或超过15%。分剂量成二等份、三等份或五等份,不同操作者等份片实际重量无统计学意义(P〉0.05)。结论:3厂家华法林钠片不同操

  3. Cognitive Behavioral Intervention in Patients with Atrial Fibrillation taking Warfarin Self-management Ability%认知行为干预对房颤服用华法令患者自我管理能力的影响

    Institute of Scientific and Technical Information of China (English)

    易小红; 魏婵娟; 漆红梅; 董立杰

    2015-01-01

    Objective To explore the cognitive behavioral intervention in patients with atrial fibril ation taking warfarin self-management ability. Methods Wil my family hospital 80 cases of atrial fibril ation in patients receiving warfarin therapy were randomly divided into intervention group and control group, 40 cases in the control group using conventional care and health education, intervention group on the basis of through slides explain, print the health education prescription, in the form of fol ow-up after discharge and cognitive intervention and behavior intervention. Respectively to evaluate patients after intervention for 3 months, assessing patients on medication, diet, monitor INR value and complications of self management ability. Results Two groups after the intervention of atrial fibril ation in patients with disease and drug knowledge and self-management ability were increased, the observation group knowledge and self-management ability score is significantly higher than control group ( <0.05). Conclusion Using cognitive behavioral intervention can significantly improve patients self management ability, improve the subjective initiative of disease, so as to keep the patient's level of INR in steady state, reduce the occur ence of complications.%目的探讨认知行为干预对心房颤动服用华法令患者自我管理能力的影响。方法将我科住院的80例心房颤动接受华法令治疗的患者随机分为干预组和对照组各40例,对照组采用常规护理和健康教育,干预组在此基础上通过幻灯片讲解,纸质版健康教育处方、出院后随访等方式进行认知干预和行为干预。分别在干预3个月后对患者进行评估,即评估患者对服药、饮食、监测INR值、并发症等方面的自我管理能力。结果干预后两组患者对心房颤动的疾病及用药等知识和自我管理能力均有提高,观察组知识掌握和自我管理能力评分显著高于对照组(<0.05)。

  4. Complicações da terapia anticoagulante com warfarina em pacientes com doença vascular periférica: estudo coorte prospectivo Complications of anticoagulant therapy with warfarin in patients with peripheral vascular disease: a cohort prospective study

    Directory of Open Access Journals (Sweden)

    Fernada Cardoso Santos

    2006-09-01

    Full Text Available OBJETIVO: Estudar prospectivamente a freqüência de complicações em pacientes tratados com warfarina e acompanhados no Ambulatório de Anticoagulação da Faculdade de Medicina de Botucatu da Universidade Estadual Paulista. MÉTODOS: Pacientes sorteados entre os agendados para consulta de junho de 2002 a fevereiro de 2004. Na primeira consulta, foi preenchida ficha com dados de identificação e clínicos. A cada retorno, ou quando o paciente procurou o hospital por intercorrência, foi preenchida ficha com a razão normatizada internacional, existência e tipo de intercorrência e condições de uso dos antagonistas da vitamina K. RESULTADOS: Foram acompanhados 136 pacientes (61 homens e 75 mulheres, 99 com tromboembolismo venoso e 37 com doença arterial; 59 pacientes eram de Botucatu, e 77, de outros municípios. Foram registradas 30 intercorrências: nove não relacionadas ao uso da warfarina e 21 complicações hemorrágicas (38,8 por 100 pacientes/ano. Uma hematêmese foi considerada grave (1,9 por 100 pacientes/ano. As demais foram consideradas moderadas ou leves. Não houve óbitos, hemorragia intracraniana ou necrose cutânea. A única associação significante foi da freqüência de hemorragia com nível médio de razão normatizada internacional. CONCLUSÃO: Nossos resultados mostram a viabilidade desse tratamento em pacientes vasculares em nosso meio, mesmo em população de baixo nível socioeconômico, quando tratados em ambulatório especializado.OBJECTIVE: To prospectively study the frequency of complications in patients treated with warfarin followed at Botucatu Medical School. METHODS: Patients randomly selected among those with appointments scheduled from June 2002 to February 2004. At the first appointment, a protocol was filled with identification and clinical data. At every return or when the patient went to the hospital due to clinical events, another form was filled with the international normalized ratio, existence

  5. Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta-analysis of observational studies.

    Science.gov (United States)

    Bavishi, Chirag; Koulova, Anna; Bangalore, Sripal; Sawant, Ashwin; Chatterjee, Saurav; Ather, Sameer; Valencia, Jose; Sarafoff, Nikolaus; Rubboli, Andrea; Airaksinen, Juhani K; Lip, Gregory Y H; Tamis-Holland, Jacqueline E

    2016-07-01

    To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI-S) who also require chronic oral anticoagulation. Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI-S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI-S or MI and requiring chronic anticoagulation. Primary outcome was all-cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow-up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all-cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61-1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51-1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35-1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03-1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38-0.92, P = 0.02]. All-cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  6. Perfil clínico de los pacientes adultos mayores anticoagulados con warfarina del Hospital Nacional de Geriatría y Gerontología Clinical Profile of Elderly Patients on Anticoagulation with Warfarin

    Directory of Open Access Journals (Sweden)

    Luis Alberto Laínez-Sánchez

    2011-12-01

    adherencia al tratamiento, red social poco comprometida y efectos adversos relacionados con la sobre anticoagulación (sangrados menores. Hubo una incidencia similar de sangrados menores y mayores (4.3% y una mortalidad del 1.4%. Conclusión: El manejo del paciente adulto mayor que recibe terapia de anticoagulación oral es de alta complejidad hecho que se ve reflejado tanto en su perfil demográfico como clínico. Las complicaciones asociadas a la terapia no difirieron con las reportadas a nivel internacional.Aim: The National Hospital of Geriatrics and Gerontology (HNGG, handles tens of patients which receives an oral anti-coagulation therapy and which come from diverse provinces of the country; the study realised a clinical and socio-demographic characterization of the anticoagulated older adult population, which receives control and treatment in the external consultation of anti-coagulated persons during the period 2006-2007. Methods:141 older adult patients were studied, all of them anti-coagulated with warfarin during the period 2006-2007. It was performed a descriptive analysis of the demographic and clinical characteristics of all the patients, making emphasis in the causes of the anti-coagulation, comorbitities, amount of medicines used, cognitive, functional and social status, quality of the anti-coagulation, reasons for the suspension of the treatment and complications. Results: The average of age of the patients was of 78 years. The larger part of the population come from the cantons of San Jose province, and possess a low academic level which does not surpass the primary schooling. The Auricular Fibrillation was the main diagnostic, which justifies the anti -coagulation therapy. The most important comorbidity was the combination between the Cardiac Insufficiency and the Arterial Hypertension. The larger part of the population uses 5 or more medicines apart from the warfarin. The group of study mainly presents an adequate cognitive status, a total functional

  7. HPLC-MS/MS测定唾液中华法林浓度及其与血药浓度关系的探讨%Quantitative determination of warfarin in human saliva and plasma by HPLC-MS/MS and the analysis of their correlation

    Institute of Scientific and Technical Information of China (English)

    王政; 李哲; 李靖; 杨春秀; 张健; 沈素; 余俊先; 王汝龙

    2016-01-01

    目的:建立唾液中华法林浓度的HPLC-MS/MS分析方法,并探讨其与血药浓度的关系。方法:采用HPLC法,色谱柱为SB-C18柱(2.1 mm×50 mm,1.8µm),流动相为乙腈(A)/0.1%甲酸水溶液(B),流速0.4 mL·min-1,梯度洗脱;质谱采用ESI正离子模式。待测样本为服用华法林患者的唾液及血浆(均于服药后12 h采集)。结果:目标化合物华法林与内标BA-TPQ的离子质荷比(m/z)分别为309.1→163和278→91.1,二者洗脱分离完全,保留时间分别为1.828 min和1.566 min。华法林的提取回收率稳定,日内、日间精密度RSD <15%。待测样本的唾液华法林浓度为5.44 ng·mL-1,5.70 ng·mL-1和8.79 ng·mL-1,与其对应的血浆样品浓度为626.04 ng·mL-1、735.51 ng·mL-1、1206.79 ng·mL-1。结论:本文建立的HPLC-MS/MS检测方法,可用于临床华法林的药物浓度监测,探索性的结果表明华法林的唾液浓度与血浆浓度的消除成平行关系,可考虑作为替代监测指标之一。%Objective:To determine the concentration of warfarin in human saliva and plasma by HPLC-MS/MS, and the correlation between saliva and plasma warfarin concentration was discussed.Methods:The separation was performed on a SB-C18 column with an gradient mobile phase consisting of acetonitrile (A) / 0.1% formic acid aqueous solution (B) at the lfow rate of 0.4 mL·min-1. Detection was carried out on a mass spectrometer by positive electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. All samples were collected 12 h after warfarin therapy.Results:Warfarin and the internal standard (IS) were detected atm/z 309.1→163 and 278→91.1, respectively. Two compounds were eluted completely and their retention time were 1.828 min and 1.566 min, respectively. The intra-day and inter-day precision relative standard deviations (RSD) were less than 15%. The warfarin concentrations in saliva samples were 5.44 ng·mL-1, 5

  8. Influence of genetic polymorphisms and non-genetic factors on the maintenance dose of warfarin%非遗传因素与基因多态性对华法林临床用药稳定维持剂量的影响

    Institute of Scientific and Technical Information of China (English)

    侯江龙; 董鑫; 王玉庆; 王刚; 董力; 李岭

    2015-01-01

    Objective To assess the influence of genetic polymorphisms and non-genetic factors on warfarin maintenance dose variations in order to provide guidance for personalized use of warfarin.Methods Two hundred patients from outpatient and inpatient with stable international normalized ratio(INR) were recruited.Clinical data and blood samples were collected.Genotypes of 4 genes involved in warfarin metabolic pathways were determined with Sanger sequencing.Based on statistical analysis of warfarin maintenance dosage, a mathematical model was established.Results Among non-genetic factors, the age and height have significant influence in warfarin dosage.The dosage is negatively correlated with age but positively correlated with height.The difference in dosage for between the 20-year-old group and 60-year-old group has reached 1.81 mg/day, and that for between the 140 cm in height and 180 cm in height groups has reached 1.06 mg/day.VKORC1-1639G/A, CYP2C9 430C/T, CYP2C9 1075A/C and CYP4F2 V433M polymorphisms have significant influence on stable warfarin dosage.The dosage for patients with wild type and mutant genotypes has varied from 0.35 mg/day to 0.84 mg/day.Conclusion Non-genetic factors and genetic polymorphisms play important roles in personalized variations of warfarin maintenance dose.The establishment of mathematical models considering multiple factors is helpful in evaluating the safety and effectiveness of warfarin dosage.%目的 评价非遗传因素和基因多态性对中国人群患者华法林用药稳定剂量的影响,为华法林个体化用药提供临床指导.方法 选取正在服用华法林进行抗凝、连续2次国际标准化比值(international normalized ratio,INR)达标的门诊及住院患者200人,记录其基本信息和临床用药情况,用Sanger直接测序法进行4种基因共8种多态性的检测,用统计学分析评价遗传与非遗传因素对华法林用药剂量的影响并建立数学模型.结果 在非遗传因素中,年龄

  9. Remission of refractory chronic cluster headache after warfarin administrations: case report Remissão de cefaléia em salvas crônica refratária após administração de varfarina: relato de caso

    Directory of Open Access Journals (Sweden)

    Jano Alves de Souza

    2004-12-01

    Full Text Available Isolated reports of a possible positive effect of anti-coagulant drugs, among them heparin, warfarin and acenocumarol, in migraine prophylaxis are found in the literature. We report the case of a 37 years old man suffering from refractory chronic cluster headache that presented remission with the administration of warfarin for the treatment of deep venous thrombosis associated to arterial thrombosis. We did not found any case like that in the literature.Alguns relatos isolados na literatura referem-se a um possível efeito profilático de drogas anticoagulantes, entre elas a heparina, varfarina e acenocumarol na profilaxia da migrânea. Apresentamos o caso de um homem de 37 anos com cefaléia em salvas crônica refratária que obteve remissão total das crises após a administração de varfarina para o tratamento de trombose venosa e arterial. Não encontramos nenhum relato semelhante na literatura consultada.

  10. Clinical curative effect observation of continuous transfusion of heparin sodium combined with urokinase and warfarin by micropump in the treatment of deep venous thrombosis%微量泵持续输注肝素钠联合尿激酶、华法林治疗下肢深静脉血栓形成的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    赵晓玲; 王明; 陈建明

    2016-01-01

    Objective:To investigate the clinical curative effect of continuous transfusion of heparin sodium combined with urokinase and warfarin by micropump in the treatment of deep venous thrombosis.Methods:86 cases of patients with deep venous thrombosis were divided into two groups randomly.The treatment group was treated with continuous transfusion of heparin sodium combined with urokinase and warfarin by micropump on the basis of conventional treatment,the control group was treated with urokinase,warfarin and low molecular heparin calcium on the basis of conventional treatment,the cure rate and effective rate of the two groups were compared.Results:The cure rate of the treatment group was 72.5%,and the total effective rate was 89.7%.The cure rate of the control group was 60.2%,and the total effective rate was 78.9%.The difference of clinical curative effect between the two groups was statistically significant(P<0.05).No serious bleeding events occurred in the two groups.Conclusion:The clinical curative effect of continuous transfusion of heparin sodium combined with urokinase and warfarin by micropump in the treatment of deep venous thrombosis was significantly better than that of low molecular heparin calcium combined with urokinase and warfarin,and the bleeding events were not significantly increased.%目的:探讨微量泵持续输注肝素钠联合尿激酶、华法林治疗下肢深静脉血栓形成的临床效果.方法:收治下肢深静脉血栓形成患者86例,随机分为两组.治疗组在常规治疗基础上,以微量泵持续输注肝素钠联合尿激酶、华法林,对照组在常规治疗基础上给予尿激酶、华法林、低分子肝素钙,比较两组治愈率及有效率.结果:治疗组治愈率 72.5%,总有效率 89.7%.对照组治愈率 60.2%,总有效率 78.9%.两组临床疗效比较,差异具有统计学意义(P<0.05).两组均未出现严重出血事件.结论:微量泵持续输注肝素钠联合尿激酶、华法林治疗下肢深静

  11. Observation on Therapeutic Effect of Warfarin on 103 Pregnant Women with Prosthetic Mechanical Heart Valves Throughout Pregnancy%心脏瓣膜置换术后妇女妊娠全程口服华法令抗凝观察103例

    Institute of Scientific and Technical Information of China (English)

    匡锋; 周新民; 尹邦良; 谢立; 伍源

    2011-01-01

    Objective To investigate the anticoagulation effect of warfarin on pregnant women with prosthetic mechanical heart valves during the whole course of pregnancy and their fetuses. Methods Follow-up survey was carried out on 103 pregnant women with prosthetic mechanical heart valves treated in the Second Xiangya Hospital of Central South University from April 1998 to June 2010. Their age ranged from 19 and 38 years (26.4±3.8 years). All the 103 pregnant women were given oral administration of warfarin during the whole course of pregnancy. The average dose of domestic warfarin was 3.30±0. 43 mg/d (87 eases), while the average dose of imported warfarin was 2.90±1.05 mg/d (16 cases). Results None of the patients suffered from serious embolic events. One patient suffered from spontaneous peritoneal hemorrhage. There were 4 cases of intrauterine deaths, and 5 cases of fetal malformation including 1 case of Down's syndrome and 4 cases of hydrocephalus. Six cases of low birth weight infants and 1 case of ABO hemolytic disease were also found. All the other neonates were healthy with normal weight. No pregnant women suffered from postpartum hemorrhage. Conclusion Oral administration of low dose warfarin (<5 mg/d) during the whole course of pregnancy is a relative safe and effective anticoagulation protocol.%目的 探讨心脏机械瓣膜置换术后的妊娠妇女全程使用华法令抗凝对孕妇及胎儿的影响.方法 随访1998年4月至2010年6月中南大学湘雅二医院103例心脏机械瓣膜置换术后妇女妊娠阶段抗凝治疗的情况,年龄19~38岁(26.4±3.8岁).103例机械瓣置换患者整个妊娠期均采用口服华法令抗凝治疗,其中国产华法令用量为3.30±0.43 mg/d(87例),进口华法令用量为2.90±1.05 mg/d(16例).结果 103例患者妊娠期间均无严重栓塞并发症,发生腹腔自发性出血1例;宫内死胎4例;出生的新生儿中发生胎儿畸形5例,其中21-三体综合征1例,脑积水4

  12. 长期服用华法林患者围手术期抗凝治疗分析及药学监护%The discussion of pharmaceutical care on perioperative management of patients with long -term warfarin treatment

    Institute of Scientific and Technical Information of China (English)

    吴癑; 徐航; 彭燕; 戎佩佩; 李萌

    2016-01-01

    目的:探讨临床药师在长期服用华法林抗凝患者围手术期的药学服务内容和作用。方法通过对长期服用华法林抗凝患者围手术期出血风险及栓塞风险评估,临床药师帮助临床医师制定规范、合理的个体化抗凝方案,并提出围手术期抗凝治疗的监护重点。结果通过合理、有效的围手术期抗凝治疗,可在不增加栓塞风险的基础上避免围手术期不良出血事件;同时还可通过药物合理选用及剂量调控,积极有效的规避抗凝药物相关的不良反应。结论在长期服用华法林抗凝患者的围手术期治疗中,临床药师应根据患者栓塞及手术风险,从术前评估、是否给予桥接治疗、术后抗凝、抗凝药物选择及剂量等方面,为患者提供个体化的抗凝治疗方面。%Objective To discuss and explore the role of clinic pharmacists in the pharmaceutical care of perioperative management of patients with long -term warfarin treatment.Methods According to the risk assessment of thrombosis and bleeding,the anticoagulant treatment of perioperative care was proposed as well as the key points of pharmaceutical care.Results The efficacy and safety of the patient's perioperative anticoagulation therapy were guaranteed by reasonable choice of drugs,dosage control and timely pharmaceutical care.With the effective management of perioperative anticoagulant treatment,the severe bleeding could be avoided without increasing risks of thrombosis.Conclusions Individual pharmaceutical care should be provided on the basis of the risk assessment of thrombosis and bleeding in addition to the patient's individual characteristic.The interruption of VKAs,the bridging anticoagulationtherapy,dosing regimen optimization and the resumption of VKAs could be considered in the perioperative management of patients with long -term anti-coagulation therapy.

  13. Investigation and Analysis on the Standardized Anticoagulant Therapy with Warfarin in the Patients with Atrial Fibrillation in a Grade 3 Hospital%某三甲医院心房颤动患者华法林规范化抗凝治疗现状调查分析

    Institute of Scientific and Technical Information of China (English)

    郑必龙; 刘俊

    2016-01-01

    目的:了解心房颤动患者抗凝治疗现状,为心房颤动规范化抗凝治疗提供参考。方法:选取皖南医学院弋矶山医院2013年1月~2014年12月非瓣膜性心房颤动患者200例,采用CHA2DS2-VASc和HAS-BLED评分系统对纳入人群进行血栓危险分层和出血风险评估,并依据《2010年欧洲心脏病学会(ESC)心房颤动治疗指南》评价其规范化抗凝情况。结果:CHA2DS2-VASc和HAS-BLED评分分别为(2.73±2.10)分和(1.57±1.13)分。183例(91.5%)患者接受抗血栓治疗,使用华法林抗凝治疗的有74例(37%),而血栓高危组125例患者中,接受华法林抗凝治疗50例(40%)。华法林抗凝治疗时间(5.78±4.73) d,累积给药剂量为(19.46±18.19) mg,55例(74.32%)患者出院前监测国际标准化比值(INR),INR达标率为30.9%。结论:心房颤动以华法林抗凝治疗现状不容乐观,应采取有效的干预措施,提高心房颤动患者抗凝治疗规范化程度。%Objective: To investigate the current state of anticoagulant therapy with warfarin in the pa-tients with atrial fibrillation in order to provide references on the standardized anticoagulant therapy. Meth-ods: A total of 200 patients diagnosed non-valvular atrial fibrillation were inspected from January 2013 to December 2014 in the Yijishan Hospital of Wannan Medical College. CHA2DS2-VASc and HAS-BLED scheme methods were used to assess the risk of thrombosis and hemorrhage in the patients and the stan-dardized anticoagulant therapy conditions were evaluated according to the 2010 update of the ESC (Euro-pean Society of Cardiology) guidelines for the management of atrial fibrillation. Results: The scores of CHA2DS2-VASc and HAS-BLED scheme were (2.73±2.10) points and (1.57±1.13) points,respectively. A-mong the 200 patients, 183 patients (91.5%) received antithrombosis therapy and 74 patients (37%) were on warfarin anticoagulant therapy. In the

  14. Warfarin Side Effects: Watch for Interactions

    Science.gov (United States)

    ... ubidecarenone) Dong quai Garlic Ginkgo biloba Ginseng Green tea St. John's wort Vitamin E Many other supplements ... Clinic does not endorse any of the third party products and services advertised. Advertising and sponsorship policy ...

  15. 出院患者华法林用药安全知识与能力水平的调查及分析%Investigation and analysis the knowledge and ability of warfarin taking safety management in the discharged patients

    Institute of Scientific and Technical Information of China (English)

    钟竹青; 段应龙; 谢建飞; 丁四清; 罗爱静

    2016-01-01

    Objective: To investigate the knowledge and ability of medication safety management in the discharged patients who were taking warfarin, and analyze the inlfuencing factors. Methods: A total of 112 discharged patients taking warfarin were investigated using the knowledge and ability of medication safety questionnaire by telephone or face-to-face interview. Results: Among all the items, most of the patients knew the correct time to take the medication, reported that they wouldn't stop the medication by themselves, and knew what to do if they forgot to take the mediation. But only few patients understood the inlfuence on diets and living habits, and the need to see a doctor. Multiple stepwise regression analysis indicated that age, medication education and instruction reading entered the equation. The older patients had lower level knowledge and ability of warfarin taking safety. Patients who got medical health guidance and read the instruction had higher level knowledge and ability of medication safety. Conclusion: The knowledge and ability of warfarin taking safety management in the discharged patients were not adequate. Medical staff should educated the patients' in detail about the medication taking safety knowledge, encouraged them to read instruction, and implemented personalized medicine safety direction effectively.%目的:调查出院患者服用华法林的用药安全知识与能力水平,分析其影响因素。方法:采用出院患者华法林用药安全知识与能力水平调查问卷对112名服用华法林的出院患者进行调查。结果:出院患者华法林用药安全知识与能力水平调查中,患者对用药的时间、不可自行停药及忘记吃药后的处理措施的掌握率比较高,对饮食和生活习惯的影响及需要就医的情况掌握率比较低。多元逐步回归分析结果显示,年龄、用药的健康指导及阅读用药说明书是患者用药安全知识与能力水平的影响因素,高龄

  16. 中国人CYP2C9基因多态性对华法林维持剂量影响的Meta分析%Effect of CYP2C9 genetic polymorphism on maintenance warfarin dosage in Chinese: A Metaanalysis

    Institute of Scientific and Technical Information of China (English)

    鲁晓春; 李世英

    2012-01-01

    目的 分析中国人CYP2C9基因多态性对华法林维持剂量的影响.方法 检索2000-2011年相关中英文数据库,用stata10.0软件进行Meta分析.结果 共纳入16项研究(共2 361人).中国人CY P2C9各等位基因型频率为野生型CYP2C9*193.99%,突异型CYP2C9*2 0.06%,CYP2C9*3 5.95%.与野生型*1/*1型相比,*1/*3和*3/*3型华法林维持剂量分别减少26.8%(95%CI 18.8%,34.8%)和26.3%(95%CI 12.6%,39.9%),亚组分析、剪补法校正及敏感性分析表明该结果稳定、可信.结论 中国人CYP2C9基因多态性频率与其他种族不同,对华法林维持剂量具有重要影响.%Objective To analyze the effect of CYP2C9 genetic polymorphism on maintenance warfarin dosage in Chinese. Methods A meta-analysis of studies about the effect of CYP2C9 genetic polymorphism on maintenance warfarin dosage in Chinese covered in related databases from 2000 to 2011 was performed using StatalO.O software. Results Sixteen studies involving 2 361 patients were included in the meta-analysis. The wild-type CYP2C9*1, mutant CYP2C9*2 and CYP2C9*3 accounted for 93.99%, 0.06%, and 5.95%, respectively, of CYP2C9 alleles in Chinese. The maintenance warfarin dosage for genotypes CYP2C9*l/*3 and CYP2C9*3/*3 was 26.8%(95%CI 18.8%, 34.8%) and 26.3%(95%CI 12.6%, 39.9%) lower than that of wild-type CYP2C9 *1/*1. Subgroup analysis and sensitivity analysis demonstrated that the results of meta-analysis were stable and reliable. Conclusion CYP2C9 genetic polymorphism in Chinese populations is different from that in other races and exerts an important effect on maintenance warfarin dosage.

  17. Evaluation on the stable dose prediction accuracy of Warfarin anticoagulant therapy by pharmacogenetics ;among Shanghai patients%药物基因组学方程对上海患者华法林抗凝治疗稳定剂量预测准确性的评估

    Institute of Scientific and Technical Information of China (English)

    庄文芳; 陈燕红; 罗瑞萍; 吴婧; 宣彬彬; 曹雅楠; 杨莉; 盛慧明

    2015-01-01

    目的:在接受华法林抗凝治疗肺栓塞和心颤患者的上海患者人群中,验证华法林药物基因组学稳定剂量预测方程的准确性。方法收集已达华法林稳定剂量的198例患者完整的临床资料,采集每位患者枸橼酸钠抗凝1∶9抗凝的外周血1.8 mL,抽提全血基因组DNA后采用高分辨率溶解曲线法检测其VKORC1-1173C>T和CYP2C9倡2、CYP2C9倡3基因型。采用较多使用的符合筛选条件的4个华法林稳定剂量预测模型[包括IWPC模型(基于混合种群构建)、WEN 模型(基于中国台湾人群构建)、HUANG模型(基于中国大陆人群构建)及OHNO模型(基于日本人群构建)]。采用绝对误差均值( MAE)和预测百分比2个指标评价并比较各模型预测准确性。结果在4个预测模型中,HUANG、OHNO及WEN 3个预测模型及固定剂量方案计算的MAE<±1.0 mg/d,理想预测百分比>40%,其中MAE最低的模型为HUANG模型。理想预测百分比最高的模型为OHNO。结论采用亚洲人群建立的基因导向结合基本临床资料的华法林稳定剂量预测模型可以较好预测服用华法林的部分上海患者的药物剂量,具有一定临床应用价值。%Objective To validate the stable dose prediction accuracy of Warfarin anticoagulant therapy by pharmacogenetics among Shanghai patients with pulmonary embolism and heart fibrillation .Methods The complete clinical data of 198 patients with stable Warfarin dose were collected .The VKORC1-1173C >T, CYP2C9*2 and CYP2C9*3 genotypes were detected by polymerase chain reaction-high resolution melting technique after whole blood genomic DNA extraction with peripheral blood 1.8 mL of sodium citrate anticoagulation 1∶9.The 4 prediction algorithms, including IWPC for mixed population , WEN for Chinese Taiwan population , HUANG for Chinese mainland population and OHNO for Japanese , were evaluated and compared by mean absolute error ( MAE

  18. 基于药物基因组学的华法林给药模型的验证%Validation and comparison of pharmacogenetics-based warfarin dosing algorithms in Han Chinese patients

    Institute of Scientific and Technical Information of China (English)

    余靓平; 宋洪涛; 曾志勇; 王齐敏; 邱罕凡

    2012-01-01

    Objective To assess whether the existing three types of pharmacogenetics-based Warfarin dosing algorithms appropriately predict the actual maintenance dose in Han Chinese mechanical heart valve replacement patients (n =130 ).Methods The patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by PCR-RFLP.The genotype of CYP2C9,VKORC1 and other information were used to calculate predicted doses.Accuracy of the models was assessed using the absolute value of the difference between predicted dose and actual dose,calculated on both an absolute and percentage basis.Actual weekly dose was also regressed on predicted weekly dose,from which we obtained R2 values.Clinical accuracy of the predictions was assessed by computing the proportion in which the predicted dose was 20% or more below the actual dose (under dosed),within 20% of the actual dose (ideally dosed ),or 20% or greater above the actual dose ( over dosed).Results The average absolute error is the smallest for the predictions made by the Wen model (3.74 mg/wk),followed by the Ohno model(4.07 mg/wk) and IWPC model(5.05 mg/wk).R2 was 40.2% in the Wen model,38.2% in the Ohno model and 26.7% in the IWPC model.When comparing the percentage of patients for whom the predicted doses were ideal,the Wen model works the best (50.0%) in low-dose group (≤21 mg/wk),but the Ohno model works the best (85.29%) in middle-dose group (21 -49 mg/wk),followed by the Wen model.Conclusion The best accuracy is achieved by the Wen model and the best clinical accuracy is obtained by the Ohno model for predicting the actual maintenance dose in Han Chinese mechanical heart valve replacement patients.%目的 对目前已建立的3种华法林个体化给药模型在中国汉族人群中进行验证,评价模型的准确性和临床实用性.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对患者进行细胞色素P450 2C9 * 3(CYP2C9*3)、维生素K环氧化物还原酶复合体亚单位1

  19. The Influence of Fol ow up Management with Special Messenger on the Treatment of Warfarin Anticoagulation in Patients with Per-manent Atrial Fibril ation%专人随访管理在持续性心房颤动病人服用华法林抗凝治疗中的作用

    Institute of Scientific and Technical Information of China (English)

    李志强; 李锦玉; 蒋庆渊; 傅咏华; 汤燕颖; 马晶; 王春燕; 胡春燕

    2016-01-01

    Objective To evaluate the influence of fol ow up management with special messenger on the treatment of warfarin antico-agulation in patients with permanent atrial fibril ation.Methods One hundred and sixty patients with permanent atrial fibril ation were recruited and divided into the routine fol ow up visit group (control group)and special messenger fol ow up management group (manage group)randomly according to the registration order.Al patients were accepted fol ow up visit for 12 months.The interna-tional normalized ratio (INR),warfarin dose,the status of INR up to the standard and the complications of each patient were recor-ded.Results The average warfarin dose,the detection frequency after INR up to the standard for the first time and the detection fre-quency of INR in the whole course in the manage group patients were significantly lower than the control group(P0.05).The status of INR up to the standard in the first month,the third month,the fourth month,the seventh month,the nineth month,the eleventh month and twelfth month were significantly different between the two groups during the 12 months fol ow up visit(P<0.01).The incidence of complications of ischemic stroke,other arterial embolism,mucocutaneous hemor-rhage,gingival hemorrhage,rhinorrhagia,haematuria and gastrointestinal hemorrhage in the manage group patients were significantly lower than the control group patients(P<0.05).Conclusion The fol ow up management with special messenger for the treatment of warfarin anticoagulation in patients with permanent atrial fibril ation could decrease the warfarin dose and the detection frequency of INR,improve the anticoagulant effect,reduce the complication of thromboembolism and hemorrhage.%目的:研究专人随访管理对持续性心房颤动(房颤)病人服用华法林抗凝效果的影响。方法随机选取160例持续性房颤病人,按就诊顺序编号分为管理组和对照组,各80例,分别接受专人随访

  20. Early diagnosis of lower extremity deep venous thrombosis and therapeutic effect of anticoagulation therapy with Roberts' age adjusted warfarin loading protocol in patients with acute ischemic stroke%急性脑梗死患者下肢深静脉血栓的诊断及华法林抗凝治疗的疗效和安全性

    Institute of Scientific and Technical Information of China (English)

    罗伟良; 刘武; 邱金华; 许南燕; 李才明; 温红

    2009-01-01

    Objective To explore the early diagnosis of lower extremity deep venous thrombosis (LDVT)and evaluate the therapeutic effect of anticoagulant therapy in hospitalized patients with acute ischemic stroke. Methods According to Wells model for suspecting lower extremity deep venous thrombosis,patients with suspected LDVT were confirmed by compression ultrasonography. If the patients diagnosed with LDVT had no contraindications to anticoagulant therapy,they were treated with low molecular weight heparin(LMWH)subcutaneous injection and oral warfarin at the same time.The dosage of oral warfarin was determined by Roberts'age adjusted warfarin loading protocol.LMWH was stopped when the patients'international normalized ratio(INR)was 2.0~3.0 for two consecutive days. Results From January 2003 to August 2007,2067 cases with acute ischemic stroke were admitted to the department of neurology in Huizhou Municipal Central Hospital including 18 cases with LDVT and the incidence was 0.9%.The patients with LDVT all had paralytic extremities including 13 left legs and 5 right legs with deep vein thrombosis.All the 18 cases were treated by anticoagulant including 17 cases with oral warfarin treatment for 3 months.Symptoms in all LDVT patients were eliminated.12 cases had been observed for one year and 5 cases for three months after they stopped taking warfatin.There were no patients with pulmonary thromboembolism and LDVT recurrence. Conclusions By using Wells model for suspecting LDVT,patients with acute ischemic stroke-complicated LDVT can be timely diagnosed.The goal of prompt and enough anticoagulant can be achieved according to Roberts'age adjusted warfarin loading protocol.Because of racial difference,population difference and other unknown factors,the incidence of acute ischemic stroke patients with complicated LDVT is much lower in Huizhou.It suggests that it should be unnecessary to use LMWH in patients with acute ischemic stroke to prevent LDVT in Huizhou.%目的 探

  1. 单管PCR-Pyrosequencing快速检测华法林代谢酶基因多态性方法的建立%Development of a single-tube PCR-pyrosequencing method for simultaneous and rapid detection of the genetic polymorphism of warfarin metabolizing enzymes

    Institute of Scientific and Technical Information of China (English)

    施宏; 虞闰六; 马金飞; 任绪义

    2011-01-01

    The purpose of this article is to develop a new high throughput method for detecting genetic polymorphism of warfarin metabolism-related genes rapidly in a single tube. Genomic DNA from human peripheral blood was extracted, and amplified with biotinylated primer to obtain single-stranded templates for pyrosequencing. Then, the single-stranded templates were subjected to Pyrosequencing analysis using PyroMark ID instrument. Simultaneously, Sanger sequencing was also applied to sequence the products as a control to check the reliability of the pyrosequencing result. The results displayed that three variants of the warfarin metabolism-related genetic polymorphism (CYP2C9*2, CYP2C9*3, and VKORC1(-1693)) could be simultaneously detected using three different sequencing primers in a single-tube (one test), and 96 tests could be carried out each time. Repeat test and reliability test indicated that the agreement between the pyrosequencing and the Sanger sequencing methods was 100%.. All of these demonstrated that pyrosequencing could accurately and rapidly detect the genetic polymorphism of the warfarin drug metabolism-related genes with high throughput. Compar- ing with simplex pyrosequencing, the method established in the present study was much more economical and timesaving. It has a great value in personalized medical treatment and could be extended to the other genetic diseases.%文章旨在建立一种单管、快速及高通量的华法林药物代谢酶相关基因多态性的检测方法.通过抽取人外周血DNA,应用带有生物素标记的扩增引物,经PCR扩增并制备焦磷酸测序单链模板,于PyroMark ID焦磷酸测序仪上进行焦磷酸测序,以Sanger测序法测序结果为对照,观察分析的准确性.结果显示,华法林药物代谢酶的3个相关基因多态性(CYP2C9*2,CYP2C9*3、VKORCl(-1693)于单管中可被同时检测,一次可获得96份DNA的华法林药物代谢相关多态性位点检测结果.经与Sanger测

  2. Varfarina ou Aspirina na prevenção de fenômenos embólicos na valvopatia mitral com fibrilação atrial Varfarina o aspirina en la prevención de fenómenos embólicos en la valvopatía mitral con fibrilación atrial Warfarin or Aspirin in embolism prevention in patients with mitral valvulopathy and atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Paulo de Lara Lavitola

    2010-12-01

    Full Text Available FUNDAMENTO: A fibrilação atrial (FA associada à doença valvar mitral reumatismal (DVMR aumenta a incidência de tromboembolismo (TE, sendo a Varfarina a medicação padrão, apesar das dificuldades na adesão e no controle terapêutico. OBJETIVO: Comparar a eficácia da Aspirina contra a Varfarina na prevenção do TE em pacientes com FA e DVMR. MÉTODOS: Acompanhamos 229 pacientes (pts, portadores de FA e DVMR, em estudo prospectivo e randomizado. 110 pts receberam Aspirina 200 mg/dia, compondo o Grupo A (GA, e 119, a Varfarina, em doses ajustáveis individualmente, compondo o Grupo V (GV. RESULTADOS: Ocorreram 15 eventos embólicos no GA e 24 no GV (p = 0,187, dos quais 21 com o INR menor que 2,0. Assim, excluindo os pacientes com INR inadequado, houve maior número de eventos embólicos no GA (15 vs 3 (p FUNDAMENTO: La fibrilación atrial (FA asociada a la enfermedad valvar mitral reumática (DVMR aumenta la incidencia de tromboembolismo (TE, siendo la Varfarina la medicación estándar, a pesar de las dificultades en la adhesión y en el control terapéutico. OBJETIVO: Comparar la eficacia de la Aspirina contra la Varfarina en la prevención del TE en pacientes con FA y DVMR. Métodos: Controlamos 229 pacientes (pts, portadores de FA y DVMR, en estudio prospectivo y randomizado. 110 pts recibieron Aspirina 200 mg/día, componiendo el Grupo A (GA, y 119, la Varfarina, en dosis ajustables individualmente, componiendo el Grupo V (GV. RESULTADOS: Ocurrieron 15 eventos embólicos en el GA y 24 en el GV (p = 0,187, de los cuales 21 con el INR menor que 2,0. Así, excluyendo los pacientes con INR inadecuado, hubo mayor número de eventos embólicos en el GA (15 vs. 3 (p BACKGROUND: Atrial fibrillation (AF associated to rheumatic mitral valve disease (RMVD increases the incidence of thromboembolism (TE, with warfarin being the standard therapy, in spite of difficulties in treatment adherence and therapeutic control. OBJECTIVE: To compare the

  3. Case analysis of one co-infected atrial fibrillation patient′s adjustment of warfarin dose with the guidance of genotype%心房颤动合并感染患者华法林剂量调整的病例分析

    Institute of Scientific and Technical Information of China (English)

    谢秋芬; 向倩; 周颖; 崔一民

    2014-01-01

    Objective To provide patients with reasonable individua-lized warfarin anticoagulation therapies according to the genotype testing.Methods Through clinical pharmacists′participation in anticoagulant therapy of an elderly female , who was admitted into hospital for aggrava-tion of heart failure due to atrial fibrillation and pulmonary infection , the reason for the elevated international normalized ratio ( INR ) was ana-lyzed , and the dose of warfarin was adjusted according to genotype results ( CYP2 C9*1/*1 and VKORC1 -1639 GA ).Before discharging her , pharmacist educated the patient so as to enhance self -anticoagulant therapy management.Results and Conclusion The patient's condition was improved.Her INR was 1.46 and in an upward trend before the day of her discharge.Guidance of genotypic testing combined with patients′concomitant diseases , medications, diet et al, could reduce time of INR to reach the target range and also improve the effectiveness and safety of anticoagulant therapy.%目的:结合基因型检测为患者提供合理的华法林个体化抗凝治疗。方法通过参与1例因心房颤动发作、肺部感染加重、心功能不全的老年女性患者抗凝治疗过程,分析国际标准化比值(INR)升高的原因,结合基因型结果(CYP2C9*1/*1和VKORC1-1639 GA)调整华法林剂量,并进行用药教育以加强自我抗凝管理。结果与结论患者病情好转出院,出院前1天INR为1.46且处于上升趋势。临床可结合患者伴随疾病、合并用药、饮食等因素,在基因型检测指导下,缩短INR达标时间,提高抗凝治疗的有效性和安全性。

  4. 临床药师参与抗凝管理服务对经皮球囊二尖瓣成形术后心房颤动患者华法林抗凝效果和安全性影响的随机对照试验%A randomized controlled trial of warfarin anti-coagulation efficacy and safety of clinical pharmacist-participated anticoagulation management for patients with atrial fibrillation after percutaneous balloon mitral valvuloplasty

    Institute of Scientific and Technical Information of China (English)

    李峥嵘; 王凌; 石增成; 鲍玉琳

    2016-01-01

    Objective To explore the warfarin anti-coagulation effect and safety of clinical pharmacist-participated anticoagulation management service(AMS)on patients with atrial fibrillation after percutaneous balloon mitral valvuloplasty(PBMV). Methods The patients who underwent PBMV were divided into trial group and control group by random number table. The patients in the trial group received the clinical pharmacist-participated AMS. The clinical pharmacist provided adjusted warfarin dosage suggestion to clinician and warfarin anticoagulant education to the patients and their family members. The patients in the control group received warfarin following the visiting doctor's advice. Anticoagulant effect indicators included international normalized ratio( INR)compliance rate,effective anticoagulation rate, anticoagulant deficiency rate and excessive anticoagulation rate. Safety evaluation indicators were embolism and bleeding events during the anticoagulant therapy. Results A total of 131 patients were enrolled in the study. The trial group comprised 68 and the control group 63 patients,respectively. The differences in the patients' age,sex composition,body weight,smoking and drinking habits,degree of mitral stenosis, combined disease,baseline INR,and preliminary warfarin dosage after PBMV were not significant between the 2 groups(all P > 0. 05). The INR compliance rate in the trial group and the control group were 53. 3%(217 / 407)and 41. 8%(155 / 371),respectively(P = 0. 001);effective anticoagulation rates were 55. 9%(38 / 68)and 33. 3%(21 / 63),respectively(P = 0. 016);anticoagulant deficiency rate were 19. 9%(81 /407)and 27. 8%(103 / 371),respectively( P = 0. 003);and the excessive anticoagulation rates were 7. 9%(32 / 407)and 14. 0%(52 / 371),respectively(P = 0. 006). There were 6 and 9 patients developed minor bleeding events and each was one slight embolism in the trial group and the control group, respectively. The incidence rate of adverse reactions in the trial

  5. Meta Analysis and System Review on Comparison of Factor Xa Inhibitors and Warfarin on the Anticoagulation Effect in Patient with Artrial Fibrillation%Xa因子抑制剂与华法林对房颤患者抗凝疗效的比较--Meta分析与系统性评价

    Institute of Scientific and Technical Information of China (English)

    刘入源; 郭凤; 阿尔达克

    2015-01-01

    Objective To evaluation system of oral factor Xa inhibitor and warfarin for the effectiveness and safety of anticoagulation in patients with atrial fibrillation treatment. Methods the method of making Cochrane system in accordance with the evaluation, Pub Med database, Ovid database, EMBASE data base, Medline CD ROM database, Tong fang database retrieval of relevant literature of computer retrieval, control experiments all articles related to search on the network and the case unpublished and manual search methods to collect relevant literature, and all references for further retrieval. Collect all relevant case-control trials were Meta analyzed using the Cochrane collaboration provided by RevMan 5.0 software;to obtain the oral factor Xa inhibitor and warfarin compared the relevant evidence on the efficacy and safety in patients with atrial fibrillation anticoagulation effect. Results factor Xa inhibitors compared with wafarlin can significantly reduce overall mortality [p=0.01, v odds ratio (OR)0.89, 95%confidence intercal (CI)(0.89,0.98),) hemor hemorrhagic stroke incidence [P<0.00001, OR 0.49, 95%CI(0.39,0.60) and the main parts of bleeding rate [P=0.07, OR 0.76,95%CI(0.57,1.02)];howener, ischemic stroke incidence [p=0.18, (OR) 1.08, 95%CI(0.97,1.20), and the incidence of myocardial infarction [P=0.19, (OR)0.94, 95%CI (0.82,1.08)], the incidence of gastrointestinal bleeding were [P=0.65, odds ratio (OR) 1.07, 95%confidence interval (CI) (0.78,1.47)]no difference. Conclusions The new oral anticoagulants Apixaban、Rivaroxaban、Edoxaban can reduce the bleeding risk and convenient medication, but at present the clinical drug use for too short a time and after the listing may be eapensive, and the lack of clear rescue drugs are insufficient to these drugs as first-line grugs considered.%目的:系统性评价口服Xa抑制剂和华法林用于房颤患者抗凝治疗的有效性和安全性。方法按照Cochrane系统评价制作方法,计算机检索Pub Med

  6. LMWH in cancer patients with renal impairment - better than warfarin?

    Science.gov (United States)

    Bauersachs, Rupert M

    2016-04-01

    Venous thromboembolism (VTE) is one of the leading causes of death in cancer patients, which are known to have a 5- to 7-fold increased risk for VTE. The anticoagulant treatment of VTE in cancer patients is less effective with a three-fold increased risk of VTE recurrence compared to non-cancer patients, and it is less safe with more than double rates of major bleeding. Compared to vitamin-K antagonists (VKA), long-term secondary prevention with low molecular weight heparin (LMWH) has been shown to reduce the risk of recurrent VTE in cancer-associated thrombosis (CAT), and therefore, current international guidelines recommend the use of LMWH over VKA. With increasing age, cancer prevalence and VTE incidence increase while renal function decreases. Anti-cancer treatment may impair renal function additionally. Therefore, renal insufficiency is a frequent challenge in CAT patients, which is associated with a higher risk of both bleeding and recurrent VTE. Both VKA and LMWH may be associated with less efficacy and higher bleeding risk in renal insufficiency. Unfortunately, there is a lack of prospective data on renal insufficiency and CAT. A recent sub-analysis from a large randomized controlled trial shows that the bleeding risk in patients with severe renal insufficiency in CAT is not elevated with the use of LMWH compared to VKA while efficacy is maintained. In addition, LMWH treatment has several practical advantages over VKA, particularly in patients with CAT while they are receiving anti-cancer treatment.

  7. Verification of five pharmacogenomics-based warfarin administration models

    Directory of Open Access Journals (Sweden)

    Meiqin Lin

    2016-01-01

    Conclusions: Since none of the models ranked high for all the three criteria considered, the impact of various factors should be thoroughly considered before selecting the most appropriate model for the region's population.

  8. 长期口服抗凝药治疗患者行经皮冠状动脉介入治疗术后应用华法林联合氯吡格雷二联抗栓治疗方案安全性及有效性的荟萃分析%Meta-analysis of the combination of warfarin and clopidogrel after coronary stenting in patients with indications for chronic oral anticoagulation

    Institute of Scientific and Technical Information of China (English)

    马改改; 杜苗苗; 张栋铭; 施育平

    2016-01-01

    Objective To investigate the safety and efficacy of dual antithrombotic regimen of warfarin and clopidogrel in patients who underwent coronary stenting and were with chronic oral anticoagulation.Methods Two investigators independently searched Pubmed,Embase and Cochrane for all reported studies,and yielding 6 articles,published before April 2015,enrolling 4825 patients,follow-up for at least 12 months.Two investigators independently recorded the data regarding interventions and the occurrence of major bleeding,ischemic stroke,myocardial infarction and death.RevMan5.3 was used to do analysis.Results Patients on dual antithrombotic regimen had insignificant reduction in major bleeding (odds ratio [OR] was 0.73,95% confidence interval [CI] was from 0.46 to 1.14,and P =0.16) as compared with triple therapy.While the risk of ischemic stroke (OR =0.78,95% CI:0.44-1.38,P =0.39),myocardial infarction (OR =1.19,95% CI:0.92-1.53,P =0.18) and the overall incidence of death (OR =0.95,95% CI:0.56-1.60,P =0.84) were also comparable between the two regimens.Conclusion Dual antithrombotic regimen of warfarin and clopidogrel is comparable to the recommended triple therapy in respect to the prevention of thromboembolic outcomes of MI/death and ischemic stroke,while the risk of bleeding is similar in those patients with indications for chronic oral anticoagulation undergoing percutaneous coronary intervention with stent implantation.%目的 评价长期口服抗凝药治疗患者行经皮冠状动脉介入治疗术后应用华法林联合氯吡格雷抗栓治疗方案的安全性和有效性.方法 检索Pubmed,Embase和Cochrane协作网,收集有关长期口服抗凝药治疗的患者行经皮冠状动脉介入治疗术后抗栓治疗的临床对照研究.记录各研究中患者的临床事件包括主要出血事件、缺血性卒中、心肌梗死、全因死亡.使用RevMan5.3统计软件做荟萃分析.结果 共纳入6个临床对照研究,其中包括1

  9. Retrobulbar Hematoma from Warfarin Toxicity and the Limitations of Bedside Ocular Sonography

    Science.gov (United States)

    2010-05-01

    and progressive swelling. She had a complicated medical history, including the recent diagnosis of deep venous thrombosis with associated pulmonary...pseudoseizures, chronic lymphadenopathy, peripheral neuropathy, and fibromyalgia . The physical exam was remarkable for slight left eye proptosis, left...need for CT scan if the diagnosis can be made. In this case, the CT scan demonstrates a fairly significant RBH (Figure 2), yet the focused bedside

  10. Frequency of the bleeding risk in patients receiving warfarin submitted to arthrocentesis of the knee

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: To evaluate the potential bleeding risks of arthrocentesis in patients with different arthropathies and taking oral anticoagulants. Materials and methods: Fifteen consecutive patients, 8 males and 7 females, treated with anticoagulant therapy for atrial fibrillation (9 pts, deep venous thrombosis (4 pts and replacement of cardiac valves (3 pts were submitted to arthrocentesis for synovial fluid effusion due to different arthropathies. In all patients INR was ≤ 5. Nine of them were assuming AINS for the joint pain. Results: Two of fifteen patients have hemarthrosis, the first only lightly, the second more frankly. Both the patients were in therapy with AINS and INR was 3,8 and 5, respectively. Conclusions: The hemarthrosis or bleeding frequency associated with intraarticular injections in patients taking anticoagulant therapy seems not very high. Therefore the therapy with oral anticoagulans would not be an absolute controindication to the arthrocentesis execution.

  11. Dietary vitamin K and therapeutic warfarin alter susceptibility to vascular calcification in experimental chronic kidney disease

    Science.gov (United States)

    The leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease (CVD), with vascular calcification (VC) being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This gamma-glutamyl carboxylase substrate is an essential ...

  12. A decision support system for boosting warfarin maintenance dose using fuzzy logic

    Directory of Open Access Journals (Sweden)

    Zahra Qaempanah

    2015-07-01

    Results: The recommended dose for 37 patients having INR therapeutic range of 2.5 to 3.5 has mean absolute error and root mean squared error of 1.89 and 2.78 respectively for three days. These error rates are 1.97 and 2.88 respectively for 38 patients who are in therapeutic range 2 to 3. Conclusion: The results are promising and encourage one to consider this system for more study with the aim of possible use as a decision support system in the future.

  13. Dental management of a patient fitted with subcutaneous Implantable Cardioverter Defibrillator device and concomitant warfarin treatment

    OpenAIRE

    Altaf Hussain Shah; Hesham Saleh Khalil; Mohammed Zaheer Kola

    2015-01-01

    Automated Implantable Cardioverter Defibrillators (AICD), simply known as an Implantable Cardioverter Defibrillator (ICD), has been used in patients for more than 30 years. An Implantable Cardioverter Defibrillator (ICD) is a small battery-powered electrical impulse generator that is implanted in patients who are at a risk of sudden cardiac death due to ventricular fibrillation, ventricular tachycardia or any such related event. Typically, patients with these types of occurrences are on antic...

  14. Dental management of a patient fitted with subcutaneous Implantable Cardioverter Defibrillator device and concomitant warfarin treatment.

    Science.gov (United States)

    Shah, Altaf Hussain; Khalil, Hesham Saleh; Kola, Mohammed Zaheer

    2015-07-01

    Automated Implantable Cardioverter Defibrillators (AICD), simply known as an Implantable Cardioverter Defibrillator (ICD), has been used in patients for more than 30 years. An Implantable Cardioverter Defibrillator (ICD) is a small battery-powered electrical impulse generator that is implanted in patients who are at a risk of sudden cardiac death due to ventricular fibrillation, ventricular tachycardia or any such related event. Typically, patients with these types of occurrences are on anticoagulant therapy. The desired International Normalized Ratio (INR) for these patients is in the range of 2-3 to prevent any subsequent cardiac event. These patients possess a challenge to the dentist in many ways, especially during oral surgical procedures, and these challenges include risk of sudden death, control of post-operative bleeding and pain. This article presents the dental management of a 60 year-old person with an ICD and concomitant anticoagulant therapy. The patient was on multiple medications and was treated for a grossly neglected mouth with multiple carious root stumps. This case report outlines the important issues in managing patients fitted with an ICD device and at a risk of sudden cardiac death.

  15. Dental management of a patient fitted with subcutaneous Implantable Cardioverter Defibrillator device and concomitant warfarin treatment

    Directory of Open Access Journals (Sweden)

    Altaf Hussain Shah

    2015-07-01

    This article presents the dental management of a 60 year-old person with an ICD and concomitant anticoagulant therapy. The patient was on multiple medications and was treated for a grossly neglected mouth with multiple carious root stumps. This case report outlines the important issues in managing patients fitted with an ICD device and at a risk of sudden cardiac death.

  16. Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Bahit, M.C.; Lopes, R.D.; Wojdyla, D.M.; Held, C.; Hanna, M.; Vinereanu, D.; Hylek, E.M.; Verheugt, F.W.; Goto, S.; Alexander, J.H.; Wallentin, L.; Granger, C.B.

    2017-01-01

    OBJECTIVE: We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other

  17. Effect of olanzapine treatment on INR of a patient receiving warfarin therapy

    Directory of Open Access Journals (Sweden)

    Derya Arslan

    2016-06-01

    Full Text Available Olanzapine is an atypical antipsychotic drug, commonly used in the management of psychotic symptoms in patients with schizoprenia and bipolar affective disorder. Deep venous thrombosis is a manifestation of venous thromboembolism. It is very well known that use of antipsychotic drugs increase the risk of thrombosis in a patient with schizophrenia. It has been reported in many studies the effects of olanzapine on thrombosis but there isn't any report about the effect of olanzapine on international normalized ratio (INR. in the medical literature. In this paper, a patient with schizophrenia and also family history of deep venous thrombosis who emerged deep venous thrombosis after being started on olanzapine treatment and effect of olanzapine treatment on INR has been reported. [Cukurova Med J 2016; 41(2.000: 370-373

  18. Drug: D01280 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ood Products/Modifiers/Volume Expanders Anticoagulants Warfarin D01280 Warfarin potassium (JP16) Target-base...Warfarin D01280 Warfarin potassium (JP16) USP drug classification [BR:br08302] Bl

  19. Randomized controlled trial of supervised patient self-testing of warfarin therapy using an internet-based expert system.

    LENUS (Irish Health Repository)

    Ryan, F

    2009-08-01

    Increased frequency of prothrombin time testing, facilitated by patient self-testing (PST) of the International Normalized Ratio (INR) can improve the clinical outcomes of oral anticoagulation therapy (OAT). However, oversight of this type of management is often difficult and time-consuming for healthcare professionals. This study reports the first randomized controlled trial of an automated direct-to-patient expert system, enabling remote and effective management of patients on OAT.

  20. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2011-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  1. Warfarin-induced sublingual hematoma mimicking Ludwig angina: Conservative management of a potentially life-threatening condition.

    LENUS (Irish Health Repository)

    Cashman, Emma

    2012-02-01

    Sublingual hematoma secondary to excessive anticoagulation is a rare, life-threatening condition. Reports in the literature have emphasized the importance of a prompt reversal of the causative coagulopathy by intravenous administration of vitamin K and fresh frozen plasma. In the event of an unstable airway, surgical intervention via tracheostomy or cricothyroidectomy is advocated. We report a case of sublingual hematoma that was treated conservatively, and we discuss the presentation and management of this entity.

  2. Randomized controlled trial of supervised patient self-testing of warfarin therapy using an internet-based expert system.

    Science.gov (United States)

    Ryan, F; Byrne, S; O'Shea, S

    2009-08-01

    Increased frequency of prothrombin time testing, facilitated by patient self-testing (PST) of the International Normalized Ratio (INR) can improve the clinical outcomes of oral anticoagulation therapy (OAT). However, oversight of this type of management is often difficult and time-consuming for healthcare professionals. This study reports the first randomized controlled trial of an automated direct-to-patient expert system, enabling remote and effective management of patients on OAT. A prospective, randomized controlled cross-over study was performed to test the hypothesis that supervised PST using an internet-based, direct-to-patient expert system could provide improved anticoagulation control as compared with that provided by an anticoagulation management service (AMS). During the 6 months of supervised PST, patients measured their INR at home using a portable meter and entered this result, along with other information, onto the internet web page. Patients received instant feedback from the system as to what dose to take and when the next test was due. During the routine care arm, patients attended the AMS at least every 4-6 weeks and were dosed by the anticoagulation pharmacist or physician. The primary outcome variable was the difference in the time in therapeutic range (TTR) between both arms. One hundred and sixty-two patients were enrolled (male 61.6%, mean age 58.7 years), and 132 patients (81.5%) completed both arms. TTR was significantly higher during PST management than during AMS management (median TTR 74% vs 58.6%; z=5.67, P expert system for the management of PST improves the control of OAT as compared with AMS management.

  3. Association of warfarin therapy duration after bioprosthetic aortic valve replacement with risk of mortality, thromboembolic complications, and bleeding

    DEFF Research Database (Denmark)

    Mérie, Charlotte; Køber, Lars; Skov Olsen, Peter

    2012-01-01

    The need for anticoagulation after surgical aortic valve replacement (AVR) with biological prostheses is not well examined.......The need for anticoagulation after surgical aortic valve replacement (AVR) with biological prostheses is not well examined....

  4. Implementing hospital guidelines improves warfarin use in non-valvular atrial fibrillation: a before-after study

    Directory of Open Access Journals (Sweden)

    Piobbici Marina

    2007-08-01

    Full Text Available Abstract Background The use of oral anticoagulant therapy (OAT to prevent non-valvular atrial fibrillation (NVAF related-strokes is often sub-optimal. We aimed to evaluate whether implementing guidelines on antithrombotic therapy (AT by a multifaceted strategy may improve appropriateness of its prescription in NVAF-patients discharged from a large tertiary-care hospital. Methods A survey was conducted on all consecutive NVAF patients discharged before (1st January–30th June 2000, n = 313 and after (1st January–30th June 2004, n = 388 guideline development and implementation. Results When strongly recommended, OAT use increased from 56.6% (60/106 in 2000 to 81.9% (86/105 in 2004, with an absolute difference of +25.3% (95%CI: 15% 35%. In patients for whom the choice OAT/acetylsalicylic acid should be individualised, those discharged without any AT were 33.7% (34/101 in 2000 and 16.9% (21/124 in 2004 (-16.7%;95%CI: -26.2% -7.2%. In a logistic regression model, OAT prescription in 2004 was increased by 2.11 times (95%CI: 1.47 3.04, after accounting for stroke risk, presence of contraindications (OR = 0.18; 0.13 0.27, older age (OR = 0.30; 0.21 0.45, prophylaxis at admission (OR = 3.03; 2.08 4.43. OAT was positively associated with the stroke risk in the 2004 sample only. Conclusion The guideline implementation has substantially improved the appropriateness of OAT at discharge, through a better evaluation at patient's individual level of the benefit-to-risk ratio.

  5. The use of sandwich-cultured rat hepatocytes to determine the intrinsic clearance of compounds with different extraction ratios: 7-ethoxycoumarin and warfarin.

    NARCIS (Netherlands)

    Treijtel, N.; Helvoort, H.A.C. van; Barendregt, A.; Blaauboer, B.J.; Eijkeren, J.C. van

    2005-01-01

    The application of sandwich-cultured rat hepatocytes for the identification of the hepatic intrinsic clearance of compounds with widely varying extraction ratios was investigated. We previously showed the applicability of this in vitro system, in combination with a model describing molecular

  6. The influence of VKORC1 and CYP2C9 gene sequence variants on the stability of maintenance phase warfarin treatment

    DEFF Research Database (Denmark)

    Skov, Jane; Bladbjerg, Else-Marie; Leppin, Anja;

    2013-01-01

    INTRODUCTION: A substantial part of the inter-individual variation in vitamin K-antagonist dose can be explained by certain sequence variants in the genes CYP2C9 (NG_008385.1:g.8633C>T or *1/*2, NG_008385.1:g.47639A>C or *1/*3) and VKORC1 (NG_011564.1:g.6399C>T). Patients possessing these variant...

  7. The use of sandwich-cultured rat hepatocytes to determine the intrinsic clearance of compounds with different extraction ratios: 7-ethoxycoumarin and warfarin.

    NARCIS (Netherlands)

    Treijtel, N.; Helvoort, H.A.C. van; Barendregt, A.; Blaauboer, B.J.; Eijkeren, J.C. van

    2005-01-01

    The application of sandwich-cultured rat hepatocytes for the identification of the hepatic intrinsic clearance of compounds with widely varying extraction ratios was investigated. We previously showed the applicability of this in vitro system, in combination with a model describing molecular diffusi

  8. Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Fosbøl, Emil Loldrup; Lip, Gregory Y H;

    2017-01-01

    BACKGROUND: Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse. PURPOSE: To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE...

  9. Woman with Sickle Cell Disease with Current Sigmoid Sinus Thrombosis and History of Inadequate Warfarin Use during a Past Thrombotic Event

    Directory of Open Access Journals (Sweden)

    Asuman Çelikbilek

    2009-05-01

    Full Text Available We report a 20-year-old woman with sickle cell disease (SCD who presented with a severe pulsating headache, nausea, and vomiting. Her history was significant for a past thrombotic event during which she had not used anticoagulation therapy as prescribed. Her mental status was mildly confused. On funduscopic examination, papilledema and retinal hemorrhages were found. Results of a computed tomogram were normal. A lumbar puncture demonstrated increased intracranial pressure (60 cm H2O. Magnetic resonance venography demonstrated a right sigmoid sinus thrombosis. Although SCD has been reported as a cause of thrombotic dural venous sinus events, this case increases the knowledge about neurological complications of SCD. The patient was treated with low molecular weight heparin, blood transfusions, acetazolamide, and methylprednisolone, and her symptoms and signs resolved.

  10. Alternatives to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a look back at the state of the field in 2012.

    Science.gov (United States)

    Truffa, Adriano A; Lopes, Renato D; Newby, L Kristin

    2013-03-01

    Stroke is the most feared complication among patients with atrial fibrillation. Oral anticoagulation therapy with vitamin K antagonists (VKAs) has been the gold standard for stroke prevention for the past 60 years. However, VKA therapy has many downsides, including risk for bleeding, a narrow therapeutic window, and the need for frequent monitoring, as well as numerous diet and lifestyle considerations that make its use cumbersome. Thus, development of new drugs that can preserve the benefits of VKAs while eliminating the negative aspects of VKA therapy has been enthusiastically sought. This article reviews the anticoagulant agents that are clinically available or under development as alternatives to VKAs for stroke prevention in patients with nonvalvular atrial fibrillation.

  11. 房颤患者华法林抗凝治疗的饮食调护%Diet Nursing of Warfarin Anticoagulation Treatment in Atrial Fibrillation Patients

    Institute of Scientific and Technical Information of China (English)

    赵东平

    2009-01-01

    华法林为香豆素类口服抗凝药,在长期服药的房颤患者中,华法林与饮食的相互作用,日益成为人们关注的焦点.阐述运用中医辨证施膳疗法,重视饮食结构,定期监测INK和PT,遵医嘱及时调整给药剂量和饮食习惯,避免不必要的出血和血栓形成,以达到令人满意的抗凝效果,提高患者生活质量.

  12. 口服华法林患者综合监测临床研究%Investigation on integrated monitoring of oral warfarin patients

    Institute of Scientific and Technical Information of China (English)

    侯文权; 周凌云; 侯文锋; 徐胜

    2010-01-01

    目的 探讨冠状动脉造影及支架植入术后口服华法林患者血浆凝血酶原前体蛋白(PIVKA-Ⅱ)、凝血酶原时间(PT)、国际标准化比率(1NR)、蛋白质Z(PZ)、细胞色素P4502C9基因CYP2C9*3的改变、临床意义及心理干预的疗效.方法 158例冠状动脉造影及支架植入术后口服华法林患者为研究组,25名门诊体检人员为对照组,分别进行血浆PZ、PIVKA-Ⅱ、PT、INR、CYP2C9*3测定.比较上述指标与临床的关系及各指标问的相关性,并对上述人员采用90项症状自评量表(SCL-90)进行心理评定.结果 研究组首次服用华法林后4 h,血浆PIVKA-Ⅱ浓度显著增高(P<0.05);首次服用华法林后24 h,PT、INR显著增高(P<0.05);首次服用华法林后16 h PZ显著增高(P<0.05).研究组PIVKA-Ⅱ、PT、INR随时间增加而增高,而PZ随时间增加显著减低.CYP2C9*3的检出率为21.9%.另外95%的患者存在不同程度的心理问题(P<0.01),主要表现为焦虑、抑郁及其他症状.PIVKA-Ⅱ与INR正相关(P<0.05).结论 上述指标能较客观地反映冠状动脉造影及支架植入术后口服华法林患者的病理变化过程.动态观察对病情判断、指导治疗和预后有一定临床意义.同时还需要对患者进行心理健康指导.

  13. Budget impact analysis of rivaroxaban vs warfarin anticoagulation strategy for direct current cardioversion in non-valvular atrial fibrillation patients: the MonaldiVert economic study.

    Science.gov (United States)

    Russo, Vincenzo; Rago, Anna; Papa, Andrea A; Bianchi, Valter; Tavoletta, Vincenzo; DE Vivo, Stefano; Cavallaro, Ciro; Nigro, Gerardo; D'Onofrio, Antonio

    2017-09-25

    Rivaroxaban is the first novel oral anticoagulant to receive regulatory approval for non-valvular atrial fibrillation (NVAF) patients who require cardioversion. The MonaldiVert real life experience showed positive benefit-risk profile of short term rivaroxaban administration for transesophageal echocardiogram guided cardioversion in patients who had not achieved adequate pre-procedural vitamin k antagonist (VKA) anticoagulation. Aim of our study was to perform a budget impact analysis of MonaldiVert anticoagulation strategy for direct current cardioversion in NVAF patients and to compare the following costs borne by the Regional Healthcare System (RHS) with those for a hypothetical cohort of identical patients underwent from the beginning to early rivaroxaban treatment before direct current cardioversion. The mean costs per each NVAF patient treated with VKA strategy and Rivaroxaban rescue strategy were 134.53€ and 189.83€, respectively. Considering a hypothetical scenario in which all population study would be treated from the beginning with rivaroxaban (Rivaroxaban early strategy), the mean cost per patient would have been 81.11€ (Table 3). The total cost borne by the RHS, including the cost of the cardioversion procedure, for the two therapeutic strategies carried out at Monaldi Hospital (VKA strategy and Rivaroxaban rescue strategy) was 88.458,53 €. The total cost would be borne by the RHS for Rivaroxaban early strategy, if applied to all population study, would have been 69.989,15 € with a saving of 18,469.38, respect to the actually applied strategy. Rivaroxaban rescue strategy for transoesophageal echocardiography guided direct current cardioversion in NVAF patients, who had not achieved adequate pre-procedural VKA anticoagulation, is an effective and safe strategy, which allows to not delay the procedure, reducing times and wastage of cardioversion slots, without substantial costs increase.

  14. 华法令在基层医院心内科的应用%Application of Warfarin in the Department of Cardiology of the Primary Hospital

    Institute of Scientific and Technical Information of China (English)

    李修壮; 汤继亮

    2009-01-01

    探讨华法令在基层医院心内科的合理应用.结合华法令的药理作用及药效动力学,用药的适应证和禁忌证,抗凝用法,抗凝强度的监测,不良反应和并发症及其处理,影响抗凝作用的因素,长期口服华法令的手术问题处理,总结使用经验.华法令的合理应用受多方面因素的影响.全面考虑华法令所能出现的问题是基层医院心内科合理应用的前提.

  15. Screening computer-assisted dosage programs for anticoagulation with warfarin and other vitamin K antagonists: minimum safety requirements for individual programs

    DEFF Research Database (Denmark)

    Poller, L; Roberts, C; Ibrahim, S;

    2009-01-01

    Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate n...... study, that is, 57.5%. The simplified procedure proposed, although not an absolute guide to safety, is designed to screen against gross unreliability of a test program, without the need to repeat a massive clinical endpoint study for each and every program.......Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non...

  16. Herbal Supplements May Not Mix with Heart Medicines

    Science.gov (United States)

    ... of bleeding Ginseng Warfarin Decreases effectiveness of warfarin Hawthorn Beta blockers, such as atenolol (Tenormin), nadolol (Corgard) ... http://www.naturaldatabase.com. Accessed Sept. 1, 2014. Hawthorn. Natural Medicines Comprehensive Database. http://www.naturaldatabase.com. ...

  17. Novel oral anticoagulants to prevent stroke in atrial fibrillation.

    NARCIS (Netherlands)

    Verheugt, F.W.A.

    2010-01-01

    Warfarin reduces the risk of stroke in atrial fibrillation by around 60%, while antiplatelet therapy is much less effective. Bleeding is, however, a notable adverse effect with warfarin. Another major drawback of warfarin is the need for frequent clotting assessment. Oral agents have been developed

  18. Current issues in patient adherence and persistence: focus on anticoagulants for the treatment and prevention of thromboembolism

    Directory of Open Access Journals (Sweden)

    Patrick P Kneeland

    2010-03-01

    Full Text Available Patrick P Kneeland, Margaret C FangThe University of California, San Francisco Division of Hospital Medicine, San Francisco, CA, USAAbstract: Warfarin therapy reduces morbidity and mortality related to thromboembolism. Yet adherence to long-term warfarin therapy remains challenging due to the risks of anticoagulantassociated complications and the burden of monitoring. The aim of this paper is to review determinants of adherence and persistence on long-term anticoagulant therapy for atrial fibrillation and venous thromboembolism. We evaluate what the current literature reveals about the impact of warfarin on quality of life, examine warfarin trial data for patterns of adherence, and summarize known risk factors for warfarin discontinuation. Studies suggest only modest adverse effects of warfarin on quality of life, but highlight the variability of individual lifestyle experiences of patients on warfarin. Interestingly, clinical trials comparing anticoagulant adherence to alternatives (such as aspirin show that discontinuation rates on warfarin are not consistently higher than in control arms. Observational studies link a number of risk factors to warfarin non-adherence including younger age, male sex, lower stroke risk, poor cognitive function, poverty, and higher educational attainment. In addition to differentiating the relative impact of warfarin-associated complications (such as bleeding versus the lifestyle burdens of warfarin monitoring on adherence, future investigation should focus on optimizing patient education and enhancing models of physician–patient shared-decision making around anticoagulation.Keywords: anticoagulation, warfarin, adherence, persistence, thromboembolism

  19. 凝血酶原前体蛋白在华法林抗凝效果监测中的应用%Application of Precursor of Prothrombin in Monitoring of Anticoagulation Effect for Warfarin

    Institute of Scientific and Technical Information of China (English)

    李伟皓; 李彦会; 李伟; 张会丰; M.J.Shearer; 刘永春

    2003-01-01

    @@ 华法林是一种常用口服抗凝剂,具有服用方便、疗效确切等优点,被广泛用于临床.目前,临床多以凝血酶原时间(PT)、国际标准化比率(INR)、凝血酶原片段1+2(F1+2)等指标对华法林抗凝效果进行评价.凝血酶原前体蛋白(Prescursor of Prothrombin.Proteins Induced by Vitamin K Abense of Antagonism,PIVKA-Ⅱ)作为反映机体维生素K营养状况最敏感的指标[1],其作用已被医学界公认,但其对评价华法林抗凝效果是否具有应用价值,目前国内尚未见报道.为此我们进行了试验研究,报道如下.

  20. Monitoring warfarin anticoagulation by testing prothrombin percursor%凝血酶原前体蛋白定量用于华法令抗凝治疗监测的初步研究

    Institute of Scientific and Technical Information of China (English)

    郝冀洪; 朱芸; 宋文杰; 李伟; 张会丰

    2004-01-01

    目的探讨凝血酶原前体蛋白(PIVKA-Ⅱ)在华法令抗凝治疗监测中的意义.方法采用ELISA法测定55例心脏瓣膜替换术后口服华法令抗凝监测患者和25名正常对照者血浆中PIVKA-Ⅱ含量,同时测定凝血酶原时间(PT)和凝血因子Ⅱ活性,比较华法令治疗组与正常对照组PIVKA-Ⅱ血浆含量、PT及因子Ⅱ活性的相关性.结果华法令组病人血浆中PIVKA-Ⅱ含量明显高于正常对照组.正常对照组中PT和因子Ⅱ活性均在正常范围内,而治疗组中PT平均为正常对照组的1.72倍,因子Ⅱ活性仅为正常对照组的43%.PIVKA-Ⅱ与PT、INR、因子Ⅱ活性相关性分别为0.788、0.715、-0.878,即PIVKA-Ⅱ与PT、INR呈显著正相关,PIVKA-Ⅱ与因子Ⅱ活性呈负相关.结论PIVKA-Ⅱ定量用于华法令抗凝治疗监测灵敏度高、稳定、结果直观,可作为华法令抗凝治疗监测的指标.

  1. Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses of low-molecular weight heparin.

    Science.gov (United States)

    Saccullo, Giorgia; Malato, Alessandra; Raso, Simona; Santoro, Marco; Zammit, Valentina; Casuccio, Alessandra; Siragusa, Sergio

    2012-04-01

    No data are available regarding the management of cancer patients requiring interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low-molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy-induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc(3) and VKA after a stable platelet count ≥ 50,000 mmc(3) . Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41-7.27], four belonging to the high-risk and one to the low-risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41-7.27), all belonging to the high-risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long-term VKA.

  2. Retraction: 'Number needed to treat with 4-factor prothrombin complex concentrate for urgent warfarin reversal' by Andrew Chua, Vishal Patel, Allison Perrin, Lee Stern, Jenifer Ehreth, Laurel Omert, Christopher Hood, Julie Farley, Michael McGlynn and Liping Huang.

    Science.gov (United States)

    2017-04-01

    The above abstract from the THSNA 2016 Summit Abstract Proceedings, first published online in the American Journal of Hematology on 20 July 2016 in Wiley OnlineLibrary (www.onlinelibrary.wiley.com), and in Volume 91, Issue 9, p. E427, has been retracted by agreement between the authors, the journal Editor-in-Chief, Carlo Brugnara, and Wiley Periodicals, Inc. The retraction has been agreed due to concerns from the submitting authors that the abstract was inadvertently submitted prior to receiving approval from all authors and proper review of data analytics, thereby rendering it incomplete.

  3. Perfil clínico de los pacientes adultos mayores anticoagulados con warfarina del Hospital Nacional de Geriatría y Gerontología Clinical Profile of Elderly Patients on Anticoagulation with Warfarin

    OpenAIRE

    Luis Alberto Laínez-Sánchez; Cynthia Villalobos-Masis

    2011-01-01

    Objetivo: El Hospital Nacional de Geriatría y Gerontología (HNGG) maneja decenas de pacientes que reciben terapia de anticoagulación oral y que provienen de diferentes provincias del país; el estudio realizó una caracterización clínica y socio demográfica de la población adulta mayor anticoagulada que recibe control y tratamiento en la consulta externa de anticoagulados durante el periodo 2006-2007. Métodos: Se estudiaron 141 pacientes adultos mayores, anticoagulados con warfarina durante el ...

  4. Binding of coumarins to human serum albumin. Study by equilibrium dialysis; Union de cumarinas a seroalbumina humana. Estudio por dialisis en el equilibrio

    Energy Technology Data Exchange (ETDEWEB)

    Zaton Lopez, A.M.L.; Ferrer Lopez, J.M. [Departamento de Bioquimica y Biologia Molecular, Universidad del Pais Vasco, Facultad de Farmacia, Vitoria (Spain)

    1995-12-31

    In order to find the typical structure of ligands that could displace the binding of warfarin on human serum albumin, the binding parameters of several coumarin derivatives have been compared. Warfarin, hydroxy coumarin, coumarin, acetyl coumarin and chromanol, bind to two different sites on seroalbumin. In the primary binding site, the affinity for the 4-hydroxyl compounds (4-chromanol, warfarin and 4-hidroxycoumarin) are larger than for coumarin and 3-acetyl coumarin. this high-affinity binding site, warfarin binding site, is the region in which the specific binding of warfarin and 4-hydroxybenzopyrans occurs. the 4-chromanol is the smallest ligand which binds to seroalbumin with high-affinity, and its structure is typical in ligands which specifically bind to the warfarin binding site. (Author) 23 refs.

  5. Sepsis as a cause of acquired Protein C and Protein S deficiency- A case report and literature review

    Directory of Open Access Journals (Sweden)

    Arun Kannan

    2014-03-01

    Full Text Available Warfarin Induced Skin Necrosis is a well-known complication in patients being started on warfarin without adequate bridging . The mechanism is thought to be due to protein C deficiency . We present a rather unusual cause of protein C deficiency due to sepsis resulting in warfarin induced skin necrosis. 43 year old lady who has been on chronic warfarin therapy secondary to anti phospholipid syndrome was admitted to the hospital for acute ischemic cerebellar stroke. Warfarin was held due to acute thrombocytopenia. She was discharged after restarting the warfarin. She presented back with septic shock due to pneumonia. She was found to have multiple necrotic areas consistent with skin necrosis. Unfortunately, patient died due to multi organ failure despite goal directed therapy. This case demonstrates the importance of recognizing the sepsis as an acquired cause of protein C deficiency.

  6. Simultaneous intrahepatic and subgaleal hemorrhage in antiphospholipid syndrome following anticoagulation therapy.

    Science.gov (United States)

    Park, In-Chul; Baek, Yang-Hyun; Han, Sang-Young; Lee, Sung-Wook; Chung, Won-Tae; Lee, Sung-Won; Kang, Sang-Hyeon; Cho, Duk-Song

    2013-10-14

    Warfarin is a widely used anticoagulant. Interindividual differences in drug response, a narrow therapeutic range and the risk of bleeding render warfarin difficult to use clinically. An 18-year-old woman with antiphospholipid syndrome received long-term warfarin therapy for a recurrent deep vein thrombosis. Six years later, she developed right flank pain. We diagnosed intrahepatic and subgaleal hemorrhages secondary to anticoagulation therapy. After stopping oral anticoagulation, a follow-up computed tomography showed improvement in the hemorrhage. After restarting warfarin because of a recurrent thrombosis, the intrahepatic hemorrhage recurred. We decided to start clopidogrel and hydroxychloroquine instead of warfarin. The patient has not developed further recurrent thrombotic or bleeding episodes. Intrahepatic hemorrhage is a very rare complication of warfarin, and our patient experienced intrahepatic and subgaleal hemorrhage although she did not have any risk factors for bleeding or instability of the international normalized ratio control.

  7. Management of antithrombotic therapy during cardiac implantable device surgery

    OpenAIRE

    AlTurki, Ahmed; PROIETTI, RICCARDO; Birnie, David H.; Essebag, Vidal

    2016-01-01

    Anticoagulants are commonly used drugs that are frequently encountered during device placement. Deciding when to halt or continue the use of anticoagulants is a balance between the risks of thromboembolism versus bleeding. Patients taking warfarin with a high risk of thromboembolism should continue to take their warfarin without interruption during device placement while ensuring their international normalized ratio remains below 3. For patients who are taking warfarin and have low risk of th...

  8. Anticoagulation therapy in Chinese patients with non-valvular atrial fibrillation: a prospective, multi-center, randomized,controlled study

    Institute of Scientific and Technical Information of China (English)

    CHEN Ke-ping; HUANG Cong-xin; HUANG De-jia; CAO Ke-jiang; MA Chang-sheng; WANG Fang-zheng; ZHANG Shu

    2012-01-01

    Background Non-valvular atrial fibrillation is associated with an increased risk of ischemic stroke; however,the appropriate intensity of anticoagulation therapy for Chinese patients has not been determined.The purpose of this study was to compare the safety and the efficacy of standard-intensity warfarin therapy,low-intensity warfarin therapy,and aspirin therapy for the prevention of ischemic events in Chinese patients with non-valvular atrial fibrillation (NVAF).Methods A total of 786 patients from 75 Chinese hospitals were enrolled in this study and randomized into three therapy groups:standard-intensity warfarin (international normalized ratio (INR) 2.1 to 2.5) group,low-intensity warfarin (INR 1.6 to 2.0) group and aspirin (200 mg per day) group.All patients were evaluated by physicians at 1,3,6,9,12,15,18,21 and 24 months after randomization to obtain a patient questionnaire,physical examination and related laboratory tests.Results The annual event rates of ischemic stroke,transient ischemic attack (TIA) or systemic thromboembolism were 2.6%,3.1% and 6.9% in the standard-intensity warfarin,low-intensity warfarin and aspirin groups,respectively (P=0.027).Thromboembolic event rates in both warfarin groups were significantly lower than that in the aspirin group (P=0.018,P=0.044),and there was no significant difference between the two warfarin groups.Severe hemorrhagic events occurred in 15 patients,7 (2.6%) in the standard-intensity warfarin group,7 (2.4%) in the low-intensity warfarin group and 1 (0.4%)in the aspirin group.The severe hemorrhagic event rates in the warfarin groups were higher than that in the aspirin group,but the difference did not reach statistical significance (P=0.101).The mild hemorrhagic and total hemorrhagic event rates in the warfarin groups (whether in the standard-intensity warfarin group or low-intensity warfarin group) were much higher than that in the aspirin group with the annual event rates of total hemorrhages of 10

  9. Alvorlige blødningskomplikationer udløst af warfarinbehandling med international normalized ratio 2,1

    DEFF Research Database (Denmark)

    Lassen, Casper Kierulf; Poulsen, Birgitte Klindt; Hvas, Anne-Mette

    2015-01-01

    The risk of bleeding due to anticoagulation therapy with warfarin rises exponentially, when the international normalized ratio (INR) exceeds 4.5. We present a 52-year-old male admitted to the hospital with severe bleeding in the lower limbs caused by warfarin. Laboratory tests showed therapeutic...

  10. Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylas genes with biochemical measures of vitamin K status

    Science.gov (United States)

    Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity ...

  11. Preliminary Assessment/Site Investigation: Tooele Army Depot, Utah. Volume 1. North Area and Facilities at Hill Air Force Base

    Science.gov (United States)

    1988-12-12

    im- portant in the area from an archaeological perspective. The Freemonts were horticulturally oriented, augmenting their diet with hunting. Freemont...dieldrin, diazinon, warfarin , malathion, DDT, and chlordane 533 Spray painting, cleaning metals, Paint pigments, phosphoric acid, welding 𔃾 metal dust...railroad beds to improve visibility, and where plants are unsightly or present a fire hazard. Pesticides, such as lindane, warfarin , malathion, and

  12. Risk of bleeding related to antithrombotic treatment in cardiovascular disease

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Olesen, Jonas B; Charlot, Mette

    2012-01-01

    a stent dual antiplatelet therapy with a P2Y12 receptor antagonist and acetylsalicylic acid (ASA) is recommended for 12 months, preferable with prasugrel or ticagrelor unless there is an additional indication of warfarin or increased risk of bleeding. In patients with AF, warfarin is recommended...

  13. Warfarinresistens hos en patient med hereditær trombofili

    DEFF Research Database (Denmark)

    Haastrup, Peter; Rudbæk, Torsten; Bove, Jeppe

    2013-01-01

    We present a case report of a young man with spontaneous deep venous thrombosis. He tested positive for heterozygote factor VLeiden mutation and was treated with warfarin. However, he turned out to be resistant to warfarin, and another venous thrombosis occurred during the insufficient treatment...

  14. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors

    DEFF Research Database (Denmark)

    Artang, Ramin; Rome, Eric; Nielsen, Jørn Dalsgaard;

    2013-01-01

    . To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization. We furthermore performed a secondary meta-analysis on atrial fibrillation stroke prevention......Dabigatran has been associated with greater risk of myocardial infarction (MI) than warfarin. It is unknown whether the increased risk is unique to dabigatran, an adverse effect shared by other oral direct thrombin inhibitors (DTIs), or the result of a protective effect of warfarin against MI...... trials with alternative anticoagulants compared with warfarin with end point of MIs after randomization. A total of 11 trials (39,357 patients) that compared warfarin to DTIs (dabigatran, ximelagatran, and AZD0837) were identified. In these trials, patients treated with oral DTIs were more likely...