Direct oral anticoagulants: An update.

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Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

[New oral anticoagulant drugs].

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Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

2011-10-01

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

Anticoagulation period in idiopathic venous thromboembolism

International Nuclear Information System (INIS)

Farraj, Rami S.

2004-01-01

The period of anticoagulation of a first episode of idiopathic venous thromboembolism has been 6 months. It is unclear if such patients would benefit from longer treatment, as there appears to be an increased risk of recurrence after anticoagulation is stopped. In a randomized prospective study of 64 patients admitted to King Hussein Medical city, Amman, Jordan, who developed a first episode of venous thromboembolism, 32 patients were given warfarin for 24-months, while 32 patients stopped anticoagulation after completion of 6-months of therapy. Our goal was to determine the effects of extended anticoagulation on rates of recurrence of symptomatic venous thromboembolism and bleeding. The patients were followed for 12-months after stopping anticoagulation. After 24-months, 7 of the 32 patients (21%) who had standard anticoagulation for 6-months had a recurrent episode of thromboembolism compared to one of the 32 patients who received anticoagulation for 24 months (3%). Extended warfarin therapy for 24-months has resulted in an absolute risk reduction of 0.1% (p<0.05). This translates into 8 patients having to be treated for 24-months to avoid one recurrence without increasing the risk of major bleeding. Two patients in each group (6%) had major nonfatal bleeding, all 4 bleeding episodes occurring within the first 3-months of anticoagulation. After 36-months of follow up, the recurrence rate of extended warfarin therapy was only 3 patients (9%), which is a 43% relative reduction in recurrence of thromboembolism compared to standard therapy for 6-months. Patients with first episodes of idiopathic venous thromboembolism have an increased risk of recurrent venous thromboembolism and should be treated with oral anticoagulants for longer than 6-months, probably 24-months. (author)

Chronic kidney disease and anticoagulation

DEFF Research Database (Denmark)

Sciascia, Savino; Radin, Massimo; Schreiber, Karen

2017-01-01

Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight...... are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin...

Direct oral anticoagulants and venous thromboembolism

Directory of Open Access Journals (Sweden)

Massimo Franchini

2016-09-01

Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

Anticoagulant Medicine: Potential for Drug-Food Interactions

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... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question Refer Patient ... Jewish Health wants you to be aware these drug-food interactions when taking anticoagulant medicine. Ask your health care ...

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

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Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

Use of anticoagulants in elderly patients: practical recommendations

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Helia Robert-Ebadi

2009-04-01

Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa

Anticoagulation and high dose liver radiation. A preliminary report

International Nuclear Information System (INIS)

Lightdale, C.J.; Wasser, J.; Coleman, M.; Brower, M.; Tefft, M.; Pasmantier, M.

1979-01-01

Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes on liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted

Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper

NARCIS (Netherlands)

Ageno, Walter; Büller, Harry R.; Falanga, Anna; Hacke, Werner; Hendriks, Jeroen; Lobban, Trudie; Merino, Jose; Milojevic, Ivan S.; Moya, Francisco; van der Worp, H. Bart; Randall, Gary; Tsioufis, Konstantinos; Verhamme, Peter; Camm, A. John

2016-01-01

Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies

Fatal consequences of synergistic anticoagulation

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Sen P

2018-05-01

Full Text Available Objective: Novel oral anticoagulants (NOACs are increasingly being preferred by clinicians (and patients because they have a wide therapeutic window and therefore do not require monitoring of anticoagulant effect. Herein, we describe the unfortunate case of a patient who had fatal consequences as a result of switching from warfarin to rivaroxaban. Case Summary: A 90-year-old Caucasian woman, with atrial fibrillation on chronic anticoagulation with warfarin, was admitted to the hospital for pneumonia. She was treated with levofloxacin. In the same admission, her warfarin was switched to rivaroxaban. On Day 3 after the switch, her INR was found to be 6, and she developed a cervical epidural hematoma from C2 to C7. She ultimately developed respiratory arrest, was put on comfort care and died. Discussion: Rivaroxaban and warfarin are known to have a synergistic anticoagulant effect, usually seen shortly after switching. Antibiotics also increase the effects of warfarin by the inhibition of metabolizing isoenzymes. It is hypothesized that these two effects led to the fatal cervical spinal hematoma. Conclusion: The convenience of a wide therapeutic window and no requirement of laboratory monitoring makes the NOACs a desirable option for anticoagulation. However, there is lack of data and recommendations on how to transition patients from Warfarin to NOACs or even how to transition from one NOAC to another. Care should be taken to ensure continuous monitoring of anticoagulation when stopping, interrupting or switching between NOACS to avoid the possibility of fatal bleeding and strokes.

Does plasmin have anticoagulant activity?

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Jane Hoover-Plow

2010-03-01

Full Text Available Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.Keywords: thrombosis, anticoagulant, cardiovascular disease, plasminogen’s protease, blood

Secondary poisoning of owls by anticoagulant rodenticides

Science.gov (United States)

Mendenhall, Vivian M.; Pank, L.F.

1980-01-01

Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone

Effects of computer-assisted oral anticoagulant therapy

DEFF Research Database (Denmark)

Rasmussen, Rune Skovgaard; Corell, Pernille; Madsen, Poul

2012-01-01

: Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (p = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured...... prescribed by physicians, and the total time spent within the therapeutic target range was similar. Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality. INR values measured by CoaguChek® were reliable compared to measurements......UNLABELLED: BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within...

Bridging Anticoagulation

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... clinical centers in the United States, Canada, and Brazil. A more detailed description of the study is ... Your Personal Message Send Message Share on Social Media Bridging Anticoagulation The BRIDGE Study Investigators Circulation. 2012; ...

The mythology of anticoagulation therapy interruption for dental surgery.

Science.gov (United States)

Wahl, Michael J

2018-01-01

Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Assessing Bleeding Risk in Patients Taking Anticoagulants

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Shoeb, Marwa; Fang, Margaret C.

2013-01-01

Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

The c.-1639g>A polymorphism of the VKORC1 gene and his influence on the therapeutic response during oral anticoagulants use

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Kovač Mirjana

2009-01-01

Full Text Available Background/Aim. A single nucleotide polymorphism c.- 1639G>A in the promoter region of vitamin K-epoxide reductase (VKORC1 gene has been found to account for most of the variability in response to oral anticoagulants (OA. The aim of the study was to determine the incidence and the effect of c.-1639G>A polymorphism on the acenocoumarol dosage requirements in the group of patients under stable anticoagulation, and to estimate the variability in response to OA. Methods. Our study included 200 consecutive patients requiring low (n = 43, medium (n = 127 and high (n = 30 acenocoumarol dose. Results. Out of 43 low dose patients, 40 (93 % carried the A allele. The A allele was less frequent in the group of 30 patients requiring high dose: among these patients 13 (43.3% carried the A allele in the heterozygous form and none of them carried AA genotype. The patients with GG genotype required 2.6 times higher dose than the patients carriers of AA genotype (p < 0.0001. In 33 patients (16.5% the overdose occurred during the initiation of anticoagulant therapy and in 11 patients (5.5% it was associated with bleeding. Out of the group of 33 overdosed patients, 27 and 6 patients carried AA and GA genotype, respectively (p < 0.000001. Conclusion. VKORC1 significantly influenced OA dose and predicted individuals predisposed to unstable anticoagulation. The carriers of AA genotype required 2.6 time lower doses of OA than the carriares of GG genotype. Pharmacogenetic testing could predict a high risk of overdose among 28.5 % of our patients - carriers of AA genotype, before anticoagulation therapy initiation.

MARINE LEECH ANTICOAGULANT DIVERSITY AND EVOLUTION.

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Tessler, Michael; Marancik, David; Champagne, Donald; Dove, Alistair; Camus, Alvin; Siddall, Mark E; Kvist, Sebastian

2018-03-16

Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to bloodfeeding from 7 piscicolid species (3 elasmobranch-feeders; 4 non-cartilaginous fish-feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, that likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution.

Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

Directory of Open Access Journals (Sweden)

Hu TY

2016-02-01

Full Text Available Tiffany Y Hu,1 Vaibhav R Vaidya,2 Samuel J Asirvatham2,31Mayo Medical School, 2Division of Cardiovascular Diseases, Department of Internal Medicine, 3Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Novel oral anticoagulants (NOACs are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075 is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran, a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445 and ciraparantag (PER977 are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials.Keywords: novel oral anticoagulant, dabigatran, idarucizumab, reversal

Anticoagulated patient's perception of their illness, their beliefs about the anticoagulant therapy prescribed and the relationship with adherence: impact of novel oral anticoagulant therapy - study protocol for The Switching Study: a prospective cohort study.

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Auyeung, Vivian; Patel, Jignesh P; Abdou, John K; Vadher, Bipin; Bonner, Lynda; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen

2016-01-01

Anticoagulant therapy is prescribed for millions of patients worldwide for the prevention and treatment of both arterial and venous thrombosis. Historically, only vitamin K antagonists have been available for clinicians to prescribe. The anticoagulation landscape is changing. The recent availability of the novel oral anticoagulants overcome many of the disadvantages associated with vitamin K antagonists. However the lack of formal monitoring and clinic follow-up is a concern for clinicians, as medication adherence is being assumed, which is known to decline in patients prescribed medications for chronic conditions. The switching study is a programme of work investigating the association between medication adherence and patient's beliefs about anticoagulation therapy (warfarin and subsequently novel oral anticoagulants), together with beliefs about their illness and anticoagulation related quality of life. The anticoagulation database at King's College Hospital will be interrogated and two groups of patients will be identified; those with a time in therapeutic range on warfarin of ≥75 % and those beliefs about medications compared. Those patients in the time in therapeutic range beliefs about medications, re-evaluated on the novel agent. The results from these sub-studies, will inform a clinical pathway to support patients on these novel agents, which will be evaluated in an independent group of patients. The results from the switching study will be used to develop a clinical pathway to support patient's prescribed novel oral anticoagulant therapy long-term.

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

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Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

The pharmacology of recombinant hirudin, a new anticoagulant ...

African Journals Online (AJOL)

A new anticoagulant, recombinant hirudin, was given to healthy volunteers (5 per test dose) in single .intravenous doses of 0,01, 0,02, 0,04, 0,07 and 0,1 mg/kg to study its anticoagulant effects, how it was tolerated and its pharmacokinetics. Hirudin proved to be a potent anticoagulant with important effects on thrombin ...

Optimal duration of anticoagulation in patients with venous thromboembolism.

Science.gov (United States)

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

2011-07-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

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

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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

Evaluation of hematuria in anticoagulated patients

International Nuclear Information System (INIS)

Cuttino, J.T.; Clark, R.L.

1986-01-01

To determine the efficacy of investigating hematuria in anticoagulated patients the authors examined records of 25 consecutive patients with hematuria who were on an anticoagulation regimen with sodium warfarin (Coumadin) for various thromboembolic disorders. All had undergone intravenous urography (IVU) and 12 had undergone cystoscopy. Potential bleeding sources were discovered in 14 patients by IVU and in seven patients by cystoscopy. Disorders found were renal stones (4), transitional carcinoma (1), lymphoma (1), retroperitoneal hematoma (1), bladder tumors (2), calcified renal mass (1), hemorrhagic cystitis (2), and enlarged prostate (7). In 18 (72%) patients, the findings on IVU and/or cystoscopy were abnormal. Hematuria is a serious symptom that warrants investigation in anticoagulated as well as nonanticoagulated patients

Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

Science.gov (United States)

Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

2018-03-01

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, Pcounselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

Evidence-Based Management of Anticoagulant Therapy

Science.gov (United States)

Schulman, Sam; Witt, Daniel M.; Vandvik, Per Olav; Fish, Jason; Kovacs, Michael J.; Svensson, Peter J.; Veenstra, David L.; Crowther, Mark; Guyatt, Gordon H.

2012-01-01

Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID:22315259

Reversal of target-specific oral anticoagulants

Science.gov (United States)

Siegal, D.M.; Cuker, Adam

2014-01-01

Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

Risk of gastrointestinal bleeding during anticoagulant treatment.

Science.gov (United States)

Lanas-Gimeno, Aitor; Lanas, Angel

2017-06-01

Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

Anticoagulant activity of ginger ( Zingiber officinale Rosc ...

African Journals Online (AJOL)

Background: Herbal medicines with anticoagulant therapeutic claims could serve as veritable sources of new oral anticoagulant drugs with possible wider safety margins than the currently available ones. Objectives: This work was aimed at evaluating a Ginger Rhizome Methanolic Extract in vivo in rats for its potential ...

The association between GGCX, miR-133 genetic polymorphisms and warfarin stable dosage in Han Chinese patients with mechanical heart valve replacement.

Science.gov (United States)

Tang, X-Y; Zhang, J; Peng, J; Tan, S-L; Zhang, W; Song, G-B; Liu, L-M; Li, C-L; Ren, H; Zeng, L; Liu, Z-Q; Chen, X-P; Zhou, X-M; Zhou, H-H; Hu, J-X; Li, Z

2017-08-01

Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR). A total of 231 patients were enrolled in the study. Blood samples were collected for genotyping. The average WSD among subjects with different GGCX or miR-133 genotypes was compared. Regression analyses were performed to test for any association of genetic polymorphisms with WSD. The warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes was 3.77±0.93 (95% CI: 3.35-4.19) mg/d and 3.70±1.00 (95% CI: 3.32-4.09) mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly associated with WSD (Pwarfarin stable dosage between subjects with MIR133B rs142410335 wild-type and variant genotypes (P>.05). The genotypes of GGCX rs699644 and rs12714145 were significantly associated with WSD (Pwarfarin stable dosage in Han Chinese patients with MHVR neither in univariate regression nor in multivariate regression analyses. © 2017 John Wiley & Sons Ltd.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

Science.gov (United States)

Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

2013-07-01

The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antithrombotic/anticoagulant and anticancer activities of selected ...

African Journals Online (AJOL)

Antithrombotic/anticoagulant and anticancer activities of selected medicinal plants from South Africa. NLA Kee, N Mnonopi, H Davids, RJ Naudé, CL Frost. Abstract. Nine plants available in the Eastern Cape Province of South Africa were tested for antithrombotic and/or anticoagulant activity. Organic (methanol) and aqueous ...

Excessive anticoagulation with warfarin or phenprocoumon may have multiple causes

DEFF Research Database (Denmark)

Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton

2012-01-01

Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation.......Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation....

Citrate Anticoagulation during Continuous Renal Replacement Therapy.

Science.gov (United States)

Ricci, Davide; Panicali, Laura; Facchini, Maria Grazia; Mancini, Elena

2017-01-01

During extracorporeal dialysis, some anticoagulation strategy is necessary to prevent the coagulation of blood. Heparin has historically been used as an anticoagulant because of its efficacy combined with low cost. However, a variable incidence of hemorrhagic complications (5-30%) has been documented in patients undergoing continuous renal replacement therapy (CRRT) with heparin as an anticoagulant. Citrate has anticoagulation properties secondary to its ability to chelate calcium, which is necessary for the coagulation cascade. Citrate may thus be used in a regional anticoagulation (RCA), limited to the extracorporeal circuit of CRRT, to avoid systemic anticoagulation. Recent meta-analysis confirmed the advantage of RCA over heparin in terms of incidence of bleeding during CRRT. Moreover, an increase in filter lifespan is documented, with a secondary advantage in reaching the prescribed dialysis dose. In our experience, we could confirm this positive effect. In fact, with a progressive increase in the proportion of CRRT with citrate as RCA, we obtained a reduction in the number of filters used for every 72 h of treatment (from 2.4 in 2011 to 1.3 in 2015), and most importantly, a reduction in the difference between the prescribed and delivered dialysis doses (from 22 to 7%). Citrate has an intense effect on the acid-base balance as well, if fully metabolized through the Krebs cycle, due to the production of bicarbonate. Even more severely ill patients, such as those with liver dysfunction, may be treated with RCA without severe complications, because modern machines for CRRT are equipped with simple systems that are able to manage the citrate infusion and control the calcium levels, with minimal risks of metabolic derangements. © 2017 S. Karger AG, Basel.

Anticoagulant therapy and its impact on dental patients: a review.

Science.gov (United States)

Thean, D; Alberghini, M

2016-06-01

Several new oral anticoagulants have been studied in the past decade, and have now started to enter the market. These drugs are reported to be as effective as, or more effective than, warfarin. In Australia, the Therapeutic Goods Administration has approved dabigatran, rivaroxaban and apixaban. The use of these newer anticoagulants is likely to increase in time, and it is important for dentists to have a sound understanding of the mechanisms of action, reversal strategies, and management guidelines for patients taking oral anticoagulants. This article discusses the process of coagulation, available anticoagulants and their monitoring and reversal, and provides clinical advice on the management of patients on anticoagulants who require dental treatment. © 2016 Australian Dental Association.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

Science.gov (United States)

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Radiation dosage

Energy Technology Data Exchange (ETDEWEB)

Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

1986-07-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

Radiation dosage

International Nuclear Information System (INIS)

Finston, Roland

1986-01-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

[Secondary osteoporosis induced by anticoagulants?].

Science.gov (United States)

Riess, H; Loew, A; Himmelreich, G

2001-07-01

Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

Anticoagulant and anti-thrombotic treatments in the management of hematological malignancies in a home care program

Directory of Open Access Journals (Sweden)

Andrea Tendas

2011-01-01

Full Text Available Aim: Anticoagulants (AC and anti-platelet (AP agents are widely administered to patients with hematological malignancies (HM. However, HM patients may be at high risk of bleeding and hemorrhagic complications, because of different form of coagulopathies and several degrees of thrombocytopenia. Materials and Methods: A prospective evaluation of the use of anticoagulant and anti-thrombotic agents as well as of bleeding and thrombotic complications in a consecutive cohort of patients, which were followed during the first semester of 2010 by our home care service, was performed. In this regard, three pharmacological class of agents, such as oral anticoagulants (warfarin and acenocumarine, low molecular weight heparin (LMWH and anti-platelet (AP drugs were considered. Results: Out of 129 patients, 26 (20% were treated with AC/AP drugs. Warfarin, acenocumarine, LMWH as well as AP were used in 7, 11 and 12 patients, respectively. Adverse events (bleeding were observed in 3 patients (11.5%, 2 cases being on warfarin (replaced by LMWH and 1 being AP (suspension without replacement; out of the 3 patients with bleeding, none presented thrombocytopenia. Conclusions: Despite the frequent findings of hemostatic disorders in a population of frail patients managed in a home care setting, our experience demonstrated that the use of AC/AP drugs has been very rarely responsible for significant complications.

Warfarin dosage response related pharmacogenetics in Chinese population.

Directory of Open Access Journals (Sweden)

Siyue Li

Full Text Available As the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1, rs7294 (VKORC1, rs1057910 (CYP2C9, rs2108622 (CYP4F2, and rs699664 (GGCX involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population.220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes.rs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D': 0.969. 158 of 220 recruited individuals had the target INR (1.5-2.5. Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender, rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR.A better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.

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.

Net clinical benefit of combination anticoagulant and antiplatelet therapy versus anticoagulation alone in atrial fibrillation patients: Results from the amadeus trial

NARCIS (Netherlands)

Lane, Deirdre; Kamphuisen, Pieter; Minini, Pascal; De Peuter, Olaf R.; Buller, Harry R.; Lip, Gregory Y. H.

2010-01-01

Background: To compare the effect of combination anticoagulant and antiplatelet (AP) therapy with anticoagulation alone on stroke and bleeding risk in atrial fibrillation (AF) patients and examine predictors of clinically relevant bleeding. Methods: Post-hoc analysis of 4576 AF patients [mean (SD)

Optical sensing of anticoagulation status: Towards point-of-care coagulation testing.

Directory of Open Access Journals (Sweden)

Diane M Tshikudi

Full Text Available Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle and maximum clot stiffness (MA were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG. To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57-0.77, p<0.04 and all LSR parameters demonstrated good correlation with TEG (r = 0.61-0.87, p<0.04. To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01. LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01. Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing.

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

Science.gov (United States)

Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

2017-05-01

Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

[Drug compliance of patients on anticoagulant treatment].

Science.gov (United States)

Gadó, Klára; Kocsis, Eszter; Zelkó, Romána; Hankó, Balázs; Kovácsné Balogh, Judit; Forczig, Mónika; Domján, Gyula

2015-08-09

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

Science.gov (United States)

Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

2017-11-01

Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

Anticoagulant Preferences and Concerns among Venous Thromboembolism Patients.

Science.gov (United States)

Lutsey, Pamela L; Horvath, Keith J; Fullam, Lisa; Moll, Stephan; Rooney, Mary R; Cushman, Mary; Zakai, Neil A

2018-03-01

 Warfarin and direct oral anticoagulants (DOACs) are used for the initial treatment and secondary prevention of venous thromboembolism (VTE), and have similar efficacy. Patient concerns and preferences are important considerations when selecting an anticoagulant, yet these are not well studied.  VTE patients ( n  = 519) were surveyed from online sources (clotconnect.org, stoptheclot.org and National Blood Clot Alliance Facebook followers [ n  = 495]) and a haematology clinic in Vermont ( n  = 24).  Patients were 83% females and on average (±standard deviation [SD]) 45.7 ± 13.1 years; 65% self-reported warfarin as their initial VTE treatment and 35% a DOAC. Proportions reporting being extremely concerned about the following outcomes were as follows: recurrent VTE 33%, major bleeding 21%, moderate bleeding 16% and all-cause death 29%. When asked about oral anticoagulant characteristics, patients strongly preferred anticoagulants that are reversible (53%), and for which blood drug levels can be monitored (30%). Lower proportions agreed with statements that regular blood testing is inconvenient (18%), that they are comfortable using the newest drug versus an established drug (15%) and that it is difficult to change their diet to accommodate their anticoagulant (17%). In multivariable-adjusted models, patients tended to have had as their initial treatment, and to currently be taking, the oral anticoagulant option they personally preferred.  Patients held the greatest concern for recurrent VTE and mortality, regardless of which treatment they were prescribed. Potential weaknesses of warfarin (e.g., dietary restrictions, regular monitoring) were generally not considered onerous, while warfarin's advantages (e.g., ability to monitor) were viewed favourably. Schattauer GmbH Stuttgart.

Evaluating the efficacy of citrate anticoagulation during CRRT in cardiac patients

Directory of Open Access Journals (Sweden)

А. М. Караськов

2015-10-01

Full Text Available Systemic anticoagulation during renal replacement therapy in cardiac patients increases the risk of postoperative complications. Citrate anticoagulation is a promising alternative. The objective of our study was to evaluate the efficacy of citrate anticoagulation and its influence on the parameters of hemostasis and complications.

Clinical impact of a pharmacist-led inpatient anticoagulation service: a review of the literature

Directory of Open Access Journals (Sweden)

Lee T

2016-05-01

Full Text Available Tiffany Lee, Erin Davis, Jason Kielly School of Pharmacy, Memorial University, St John's, NL, Canada Background: Anticoagulant therapies provide management options for potentially life-threatening thromboembolic conditions. They also carry significant safety risks, requiring careful consideration of medication dose, close monitoring, and follow-up. Inpatients are particularly at risk, considering the widespread use of anticoagulants in hospitals. This has prompted the introduction of safety goals for anticoagulants in Canada and the USA, which recommend increased pharmacist involvement to reduce patient harm. The goal of this review is to evaluate the efficacy and safety of pharmacist-led inpatient anticoagulation services compared to usual or physician-managed care. Methods: This narrative review includes articles identified through a literature search of PubMed, Embase, and International Pharmaceutical Abstracts databases, as well as hand searches of the references of relevant articles. Full publications of pharmacist-managed inpatient anticoagulation services were eligible if they were published in English and assessed clinical outcomes. Results: Twenty-six studies were included and further divided into two categories: 1 autonomous pharmacist-managed anticoagulation programs (PMAPs and 2 pharmacist recommendation. Pharmacist management of heparin and warfarin appears to result in improvements in some surrogate outcomes (international normalized ratio [INR] stability and time in INR goal range, while results for others are mixed (time to therapeutic INR, length of stay, and activated partial thromboplastin time [aPTT] measures. There is also some indication that PMAPs may be associated with reduced patient mortality. When direct thrombin inhibitors are managed by pharmacists, there seems to be a shorter time to therapeutic aPTT and a greater percentage of time in the therapeutic range, as well as a decrease in the frequency of medication

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

Science.gov (United States)

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

[The study of anticoagulants selection in platelet-rich plasma preparation].

Science.gov (United States)

Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

2015-07-01

To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

Efficacy of protocol-based pharmacotherapy management on anticoagulation with warfarin for patients with cardiovascular surgery.

Science.gov (United States)

Katada, Y; Nakagawa, S; Minakata, K; Odaka, M; Taue, H; Sato, Y; Yonezawa, A; Kayano, Y; Yano, I; Nakatsu, T; Sakamoto, K; Uehara, K; Sakaguchi, H; Yamazaki, K; Minatoya, K; Sakata, R; Matsubara, K

2017-10-01

Anticoagulation therapy with warfarin requires periodic monitoring of prothrombin time-international normalized ratio (PT-INR) and adequate dose adjustments based on the data to minimize the risk of bleeding and thromboembolic events. In our hospital, we have developed protocol-based pharmaceutical care, which we called protocol-based pharmacotherapy management (PBPM), for warfarin therapy. The protocol requires pharmacists to manage timing of blood sampling for measuring PT-INR and warfarin dosage determination based on an algorithm. This study evaluated the efficacy of PBPM in warfarin therapy by comparing to conventional pharmaceutical care. From October 2013 to June 2015, a total of 134 hospitalized patients who underwent cardiovascular surgeries received post-operative warfarin therapy. The early series of patients received warfarin therapy as the conventional care (control group, n=77), whereas the latter received warfarin therapy based on the PBPM (PBPM group, n=68). These patients formed the cohort of the present study and were retrospectively analysed. The indications for warfarin included aortic valve replacement (n=56), mitral valve replacement (n=4), mitral valve plasty (n=22) and atrial fibrillation (n=29). There were no differences in patients' characteristics between both groups. The percentage time in therapeutic range in the first 10 days was significantly higher in the PBPM group (47.1%) than that in the control group (34.4%, PWarfarin therapy based on our novel PBPM was clinically safe and resulted in significantly better anticoagulation control compared to conventional care. © 2017 John Wiley & Sons Ltd.

New oral anticoagulant-induced bleeding: clinical presentation and management

NARCIS (Netherlands)

Levy, Jerrold H.; Levi, Marcel

2014-01-01

Bleeding is a significant complication of anticoagulant therapy. With the emergence of new oral anticoagulants (NOACs; ie, direct factor IIa or Xa inhibitors), this risk is further compounded by the lack of validated reversal strategies for these agents. Emerging postmarketing evidence suggests that

Disadvantages of VKA and requirements for novel anticoagulants.

Science.gov (United States)

Shameem, Raji; Ansell, Jack

2013-06-01

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

Hematometra secondary to anticoagulant rodenticide toxicity

International Nuclear Information System (INIS)

Padgett, S.L.; Stokes, J.E.; Tucker, R.L.; Wheaton, L.G.

1998-01-01

An adult, intact female Australian shepherd presented for frank vaginal bleeding of unknown duration. The only coagulation profile abnormality upon presentation was mild prolongation of the partial thromboplastin time (PTT). The uterus was removed at surgery and contained a large amount of coagulated blood. Clotting profiles were markedly abnormal48 hours postoperatively. Serum analysis was positive for brodifacoum, an anticoagulant rodenticide. Preoperative coagulation was most likely normalized by vitamin K-1 therapy administered prior to presentation. The only manifestation of anticoagulant rodenticide was hematometra. Rodenticide intoxication should be considered in the differential diagnosis list of hematometra or metrorrhagia

Standards of care issues with anticoagulation in real-world populations.

Science.gov (United States)

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

Vitamin K requirement in Danish anticoagulant-resistant Norway rats (Rattus norvegicus)

DEFF Research Database (Denmark)

Markussen, Mette D.; Heiberg, Ann-Charlotte; Nielsen, Robert

2003-01-01

Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement......Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement...

New anticoagulants for the prevention and treatment of venous thromboembolism

Directory of Open Access Journals (Sweden)

Simon J McRae

2005-04-01

Full Text Available Simon J McRae, Jeffrey S GinsbergDepartment of Medicine, McMaster University, Hamilton, ON, CanadaAbstract: Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety, ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism.Keywords: venous thromboembolism, anticoagulants, antithrombotic

Adherence to a new oral anticoagulant treatment prescription: dabigatran etexilate

Directory of Open Access Journals (Sweden)

L Bellamy

2009-07-01

Full Text Available L Bellamy1, N Rosencher1, BI Eriksson21Anaesthesiology Department, Hôpital Cochin (AP-HP, René Descartes University, Paris 75014 France; 2Orthopaedic Department, University Hospital Sahlgrenska/Ostra, Gothenburg, SwedenAbstract: The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.Keywords: oral anticoagulant, adherence, compliance, education, dabigatran

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

Science.gov (United States)

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pharmacology of new oral anticoagulants: mechanism of action, pharmacokinetics, pharmacodynamics

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Luca Masotti

2013-12-01

Full Text Available Due to their mechanism of action, the new oral anticoagulants are named direct oral anticoagulants (DOACs. Dabigatran is a selective, competitive, direct inhibitor of thrombin (Factor IIa while rivaroxaban, apixaban and edoxaban act by directly inhibiting the activated Factor X (FXa in a selective and competitive manner. DOACs have a relatively short half-life and almost immediate anticoagulant activity, and rapidly reach the plasma peak concentration. Therefore, they do not need a phase of overlapping with parenteral anticoagulants. After their withdrawal, their removal is sufficiently rapid, although influenced by renal function. Dabigatran is the only DOACs to be administered as a pro-drug and becomes active after drug metabolization. The route of elimination of dabigatran is primarily renal, whereas FXa inhibitors are mainly eliminated by the biliary-fecal route. The drug interactions of DOACs are mainly limited to drugs that act on P-glycoprotein for dabigatran and on P-glycoprotein and/or cytochrome P3A4 for anti-Xa. DOACs have no interactions with food. Given their linear pharmacodynamics, with a predictable dose/response relationship and anticoagulant effect, DOACs are administered at a fixed dose and do not require routine laboratory monitoring.

Atrial Fibrillation in Embolic Stroke: Anticoagulant Therapy at UNTH ...

African Journals Online (AJOL)

Objective: The decision to commence anticoagulation in a patient with embolic stroke and atrial fibrillation (AF) is often a difficult one for many clinicians. The result can have significant impact on the patient. This study was therefore undertaken to review the use of anticoagulation in embolic stroke in the setting of atrial ...

Survey of the use of warfarin and the newer anticoagulant dabigatran in patients with atrial fibrillation

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Choi JC

2014-02-01

Full Text Available Jiyoon C Choi,1 Marco d DiBonaventura,2 Lewis Kopenhafer,2 Winnie W Nelson31LifeScan, Inc, West Chester, PA, 2Health Sciences Practice, Kantar Health, New York, NY, 3Janssen Scientific Affairs LLC, Raritan, NJ, USABackground: Oral dabigatran was recently approved as an alternative to warfarin for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran has a fixed dosage and few drug interactions, and does not require anticoagulation monitoring or dietary restrictions.Methods: This study aimed to describe and compare characteristics of patients with atrial fibrillation who used dabigatran or only warfarin. Patients with a self-reported diagnosis of atrial fibrillation aged ≥18 years who were receiving (or had received warfarin or dabigatran completed an online survey. Differences in characteristics of dabigatran and warfarin users were tested using chi-squared tests and analysis of variance for categorical and continuous variables, respectively.Results: Overall, 364 patients were surveyed (204 warfarin users, 160 dabigatran users. The mean age was 65.1 years, and 68.7% were male. Dabigatran users were more likely than warfarin users to be female (36.9% versus 27.0% and to have experienced adverse events, including gastrointestinal bleeding, in the 3 months before the survey (21.9% versus 6.9%; P<0.05. Both groups reported high medication adherence (dabigatran users 0.65 versus warfarin users 0.63 missed doses/month. Dabigatran users were more likely than warfarin users to discuss treatment options with their physician before beginning therapy (36.9% versus 24.5%; P<0.05 and less likely to switch anticoagulant medication (10.7% versus 31.9%; P<0.05. Although dabigatran users were more likely to experience adverse events, they reported greater satisfaction with anticoagulation treatment than warfarin users.Conclusion: The efficacy and convenience reported by dabigatran users

The Interaction Effects of Program Training, Dosage, and Implementation Quality on Targeted Student Outcomes for The RULER Approach to Social and Emotional Learning

Science.gov (United States)

Reyes, Maria Regina; Brackett, Marc A.; Rivers, Susan E.; Elbertson, Nicole A.; Salovey, Peter

2012-01-01

This study examined how training, dosage, and implementation quality of a social and emotional learning program, The RULER Approach, were related to students' social and emotional competencies. There were no main effects for any of the variables on student outcomes, but students had more positive outcomes when their teachers (a) attended more…

Bleeding events associated with novel anticoagulants: a case series.

Science.gov (United States)

Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

2013-12-01

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

Science.gov (United States)

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-02

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

Bleeding in patients using new anticoagulants or antiplatelet agents: Risk factors and management

NARCIS (Netherlands)

Levi, M.M.; Eerenberg, E.; Löwenberg, E.; Kamphuisen, P.W.

2010-01-01

The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. in case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be

Anticoagulant rodenticides and wildlife: Introduction

Science.gov (United States)

van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

2018-01-01

Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

Science.gov (United States)

White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

2016-03-01

Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

Reproductive success of bromadiolone-resistant rats in absence of anticoagulant pressure

DEFF Research Database (Denmark)

Heiberg, Ann-Charlotte; Leirs, Herwig; Siegismund, Hans Redlef

2006-01-01

Resistance to anticoagulant rodenticides in brown rats (Rattus norvegicus Berk.) is associated with pleiotropic effects, notably with an increased dietary vitamin K requirement. Owing to this disadvantage, resistance is believed to be selected against if anticoagulant selection is absent. In small...... experimental populations of wild brown rats, an investigation was carried out to establish whether tolerance to anticoagulant exposure changed over a period of 2 years. In the same populations, DNA microsatellite markers were used to infer parentage, and this made it possible to estimate reproductive success...... of sensitive and resistant rats and estimate effective population size, Ne. Even though there was evidence for a selection against resistant rats with high vitamin K requirement, anticoagulant tolerance was not seen to be significantly influenced in the absence of bromadiolone selection. As the population size...

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

Science.gov (United States)

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

Utilization of oral anticoagulation in a teaching hospital in Nigeria ...

African Journals Online (AJOL)

The mean age of the patients was 53.4 years and more females than males were on anticoagulation and monitoring (F14:M12). The most common indications for anticoagulation include deep venous thrombosis/pulmonary embolism, congestive heart failure with atrial fibrillation and mitral valve disease with atrial fibrillation.

Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients

DEFF Research Database (Denmark)

Olesen, Jonas Bjerring; Sørensen, Rikke; Hansen, Morten Lock

2015-01-01

AIMS: Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. METHODS AND RESULTS: Using Danish nationwide administrative registers, we identif...

Hemorrhagic stroke and oral anticoagulants: What is to be done?

Directory of Open Access Journals (Sweden)

M. A. Domashenko

2016-01-01

Full Text Available Hemorrhagic stroke (HS is associated with high mortality and disability rates. Due to the introduction of the current guidelines for the prevention of systemic thromboembolic events in patients with atrial fibrillations and to an increase in the number of older patients, there has been a rise in the incidence of intracranial hemorrhage (ICH associated with the use of oral anticoagulants. The paper discusses medical treatment in patients with HS during therapy with vitamin K antagonists (warfarin and novel oral anticoagulants (dabigatran. rivaroxaban, apixaban, as well as an anticoagulant resumption policy after prior ICH in patients at high risk for thromboembolic events.

Anticoagulants Influence the Performance of In Vitro Assays Intended for Characterization of Nanotechnology-Based Formulations

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Edward Cedrone

2017-12-01

Full Text Available The preclinical safety assessment of novel nanotechnology-based drug products frequently relies on in vitro assays, especially during the early stages of product development, due to the limited quantities of nanomaterials available for such studies. The majority of immunological tests require donor blood. To enable such tests one has to prevent the blood from coagulating, which is usually achieved by the addition of an anticoagulant into blood collection tubes. Heparin, ethylene diamine tetraacetic acid (EDTA, and citrate are the most commonly used anticoagulants. Novel anticoagulants such as hirudin are also available but are not broadly used. Despite the notion that certain anticoagulants may influence assay performance, a systematic comparison between traditional and novel anticoagulants in the in vitro assays intended for immunological characterization of nanotechnology-based formulations is currently not available. We compared hirudin-anticoagulated blood with its traditional counterparts in the standardized immunological assay cascade, and found that the type of anticoagulant did not influence the performance of the hemolysis assay. However, hirudin was more optimal for the complement activation and leukocyte proliferation assays, while traditional anticoagulants citrate and heparin were more appropriate for the coagulation and cytokine secretion assays. The results also suggest that traditional immunological controls such as lipopolysaccharide (LPS are not reliable for understanding the role of anticoagulant in the assay performance. We observed differences in the test results between hirudin and traditional anticoagulant-prepared blood for nanomaterials at the time when no such effects were seen with traditional controls. It is, therefore, important to recognize the advantages and limitations of each anticoagulant and consider individual nanoparticles on a case-by-case basis.

APPLICATIONS OF PHARMACOGENETIC TESTING FOR PERSONALIZATION OF THERAPY WITH ORAL ANTICOAGULANTS IN RUSSIA

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D. A. Sychev

2013-01-01

Full Text Available The clinical significance of the patient genetic characteristics in the individual pharmacological response to oral anticoagulants is considered. Possible tactics of warfarin dosing and new oral anticoagulants choice on the basis of pharmacogenetic testing as well as indications for this approach in clinical practice are discussed. It should increase efficacy and safety of anticoagulant therapy.

Direct Oral Anticoagulants and Women

NARCIS (Netherlands)

Cohen, Hannah; Arachchillage, Deepa R. J.; Beyer-Westendorf, Jan; Middeldorp, Saskia; Kadir, Rezan A.

2016-01-01

Direct oral anticoagulants (DOACs) provide an effective, safe, and convenient therapeutic alternative to warfarin and other vitamin K antagonists (VKAs), and are now established for a wide range of indications. The use of DOACs in women merits special consideration due to two main situations: first,

Anticoagulation Quality and Complications of using Vitamin K Antagonists in the Cardiac Surgery Outpatient Clinic

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Mário Augusto Cray da Costa

Full Text Available ABSTRACT Introduction: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. Objective: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. Methods: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. Results: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli; 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001. Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04. Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03, less annual consultations (P=0.02 and less dose adjustments (P=0.003. Patients with longer duration of anticoagulation have more complications (P=0.001. Conclusion: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of

Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance.

Science.gov (United States)

Hagerty, Tracy; Rich, Michael W

2017-01-01

Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The most common reason physicians cite for withholding anticoagulation in older patients with atrial fibrillation is a perception of a high risk of falling and associated bleeding, especially intracranial hemorrhage. Copyright © 2017 Cleveland Clinic.

Hematin-derived anticoagulant. Generation in vitro and in vivo

OpenAIRE

1986-01-01

Prolongation of clotting times produced by hematin was investigated both in vitro and in vivo. Hematin-derived anticoagulant (HDA) was found to be due to a degradative product or derivative of hematin, and was generated in vitro in standing (aging) aqueous solutions of the parent compound. Generation of HDA in vitro was inhibited by antioxidants. The anticoagulant effect of HDA was inhibited by freshly prepared hematin, fresh Sn-protoporphyrin, imidazole, or the iron chelator desferrioxamine....

Heterofucans from Dictyota menstrualis have anticoagulant activity

Directory of Open Access Journals (Sweden)

I.R.L. Albuquerque

2004-02-01

Full Text Available Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml, whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.

D-dimer: a useful tool in gauging optimal duration of oral anticoagulant therapy?

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M. Silingardi

2013-05-01

Full Text Available BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT in idiopathic venous thromboembolism (VTE is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this

Oral Anticoagulation in Patients With Liver Disease.

Science.gov (United States)

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

Science.gov (United States)

Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

2017-08-01

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants

The effect anticoagulation status on geriatric fall trauma patients.

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Coleman, Julia; Baldawi, Mustafa; Heidt, David

2016-12-01

This research study aims to identify the effect of anticoagulation status on hospital course, complications, and outcomes among geriatric fall trauma patients. The study design is a retrospective cohort study, looking at fall trauma among patients aged 60 to 80 years from 2009 to 2013 at a university hospital in the United States. The statistical analysis, conducted with SPSS software with a threshold for statistical significance of P patients included in this study was 1,121. Compared with patients not on anticoagulation, there was a higher LOS among patients on anticoagulation (6.3 ± 6.2 vs 4.9 ± 5.2, P = .001). A higher LOS (7.2 ± 6.8 vs 5.0 ± 5.3, P = .001) and days in the ICU (2.1 ± 5.4 vs 1.1 ± 3.8, P = .010) was observed in patients on warfarin. A higher mortality (7.1% vs 2.8%, P = .013), LOS (6.3 ± 6.2 vs 5.1 ± 5.396, P = .036), and complication rate (49.1 vs 36.7, P = .010) was observed among patients on clopidogrel. In this study, a higher mortality and complication rate were seen among clopidogrel, and a greater LOS and number of days in the ICU were seen in patients on warfarin. These differences are important, as they can serve as a screening tool for triaging the severity of a geriatric trauma patient's condition and complication risk. For patients on clopidogrel, it is essential that these patients are recognized early as high-risk patients who will need to be monitored more closely. For patients on clopidogrel or warfarin, bridging a patient's anticoagulation should be initiated as soon as possible to prevent unnecessary increased LOS. At last, these data also provide support against prescribing patients clopidogrel when other anticoagulation options are available. Published by Elsevier Inc.

Will NOACs become the new standard of care in anticoagulation therapy?

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Ergene Oktay

2015-06-01

Full Text Available Atrial fibrillation is the most common cardiac arrhythmia in the general population, with a prevalence of 1–3%, which increases with age, reaching 15% in elderly people. Prophylaxis of ischemic stroke with warfarin was the gold standard of medical management for many years. On the other hand heparin and warfarin was the main pharmacologic agents for the prophylaxis/treatment of venous thromboembolism. In the last 5 years warfarin is getting replaced by non-vitamin K antagonist oral anticoagulants at least partly. In this article it is attempted to foresee whether new oral anticoagulants will become the new standard of care in anticoagulation therapy.

Citrate Anticoagulation for CRRT in Children: Comparison with Heparin

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Sara Nicole Fernández

2014-01-01

Full Text Available Regional anticoagulation with citrate is an alternative to heparin in continuous renal replacement therapies, which may prolong circuit lifetime and decrease hemorrhagic complications. A retrospective comparative cohort study based on a prospective observational registry was conducted including critically ill children undergoing CRRT. Efficacy, measured as circuit survival, and secondary effects of heparin and citrate were compared. 12 patients on CRRT with citrate anticoagulation and 24 patients with heparin anticoagulation were analyzed. Median citrate dose was 2.6 mmol/L. Median calcium dose was 0.16 mEq/kg/h. Median heparin dose was 15 UI/kg/h. Median circuit survival was 48 hours with citrate and 31 hours with heparin (P=0.028. 66.6% of patients treated with citrate developed mild metabolic alkalosis, which was directly related to citrate dose. There were no cases of citrate intoxication: median total calcium/ionic calcium index (CaT/I of 2.16 and a maximum CaT/I of 2.33, without metabolic acidosis. In the citrate group, 45.5% of patients developed hypochloremia and 27.3% hypomagnesemia. In the heparin group, 27.8% developed hypophosphatemia. Three patients were moved from heparin to citrate to control postoperatory bleeding. In conclusion citrate is a safe and effective anticoagulation method for CRRT in children and it achieves longer circuit survival than heparin.

Adverse effects of anticoagulation treatment: clinically significant upper gastrointestinal hemorrhage

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Pavel Skok

2006-12-01

Full Text Available Background: Over the last years, the use of oral anticoagulant treatment has increased dramatically, principally for the prevention of venous thrombosis and thrombembolic events. This treatment is demanding, especially among the elderly with concommitant diseases and different medication. Aim of the study to evaluate the rate of serious complications, clinically significant hemorrhage from upper gastointestinal tract in patients treated with oral antiocoagulants in a prospective cohort study.Patients and methods: Included were patients admitted to our institution between January 1, 1994 and December 31, 2003 due to gastrointestinal hemorrhage. Emergency endoscopy and laboratory testing was performed in all patients.Results: 6416 patients were investigated: 2452 women (38.2 % and 3964 men (61.8 %, mean age 59.1 years, SD 17.2. Among our patients, 55 % were aged over 60 years. In 86.4 % of patients the source of bleeding was confirmed in the upper gastrointestinal tract. In the last week prior to bleeding, 20.4 % (1309/6416 of all patients were regularly taking nonsteroidal anti-inflammatory drugs, anticoagulant therapy or antiplatelet agents in single daily doses at least. 6.3 % of patients (82/1309 with abundant hemorrhage from upper gastrointestinal tract were using oral anticoagulant therapy and had INR > 5 at admission, 25.6 % of them had INR > 10. The mortality of patients using oral anticoagulants and INR > 5 was 17.1 %.Conclusions: Upper gastrointestinal hemorrhage is a serious complication of different medications, particularly in elderly patients. Safe use of anticoagulant therapy is based on careful selection of patients and correct intake of the prescribed drugs.

Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?

Science.gov (United States)

Sciascia, S; Coloma-Bazán, E; Radin, M; Bertolaccini, M L; López-Pedrera, C; Espinosa, Gerard; Meroni, P L; Cervera, R; Cuadrado, M J

2017-11-01

The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion). We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed. To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparative assessment of efficacy of three anticoagulant rodenticides.

Science.gov (United States)

Renapurkar, D M

1982-01-01

Results are presented of feeding tests carried out with three common anticoagulant rodenticides viz., coumatetralyl, fumarin and warfarin on three common species of commensal rodents i.e., Rattus rattus, Rattus norvegicus and Bandicota bengalensis. All three species of rodents were susceptible to anticoagulant rodenticides. However, the action of these compounds in B. bengalensis was comparatively slow. Coumatetralyl was found to be the most effective rodenticide followed by fumarin and warfarin. Liquid baits of these compounds are more effective in comparison to food baits.

Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.

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Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D

2016-12-01

Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

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Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

2017-08-01

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of Periprocedural Anticoagulation: A Survey of Contemporary Practice.

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Flaker, Greg C; Theriot, Paul; Binder, Lea G; Dobesh, Paul P; Cuker, Adam; Doherty, John U

2016-07-12

Interruption of oral anticoagulation (AC) for surgery or an invasive procedure is a complicated process. Practice guidelines provide only general recommendations, and care of such patients occurs across multiple specialties. The availability of direct oral anticoagulants further complicates decision making and guidance here is limited. To evaluate current practice patterns in the United States for bridging AC, a survey was developed by the American College of Cardiology Anticoagulation Work Group. The goal of the survey was to assess how general and subspecialty cardiologists, internists, gastroenterologists, and orthopedic surgeons currently manage patients who receive AC and undergo surgery or an invasive procedure. The survey was completed by 945 physicians involved in the periprocedural management of AC. The results provide a template for educational and research projects geared toward the development of clinical pathways and point-of-care tools to improve this area of health care. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Use of antifibrinolytic mouthwash solution in anticoagulated oral surgery patients

OpenAIRE

Dimova, Cena; Evrosimovska, Biljana; Papakoca, Kiro; Georgiev, Zlatko; Angelovska, Bistra; Ristoska, Sonja

2012-01-01

Introduction:The ordinary treatment of anticoagulated patients includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may logically increase the risk of a potentially life-threatening thromboembolism, so this issue is still controversial. The aim of the study was to evaluate the antifibrinolitic mouthwash solution (tranexamic acid) as a local haemostatic modality after oral surgery interventions. Methods:To realize the a...

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation.

Science.gov (United States)

Marsh, E B; Llinas, R H; Hillis, A E; Gottesman, R F

2013-06-01

Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism

NARCIS (Netherlands)

Kuijer, P. M.; Hutten, B. A.; Prins, M. H.; Büller, H. R.

1999-01-01

OBJECTIVES: To construct and validate the bleeding risk prediction score, which is based on variables identified in the literature that can be easily obtained before the institution of anticoagulant therapy, in a large independent cohort of patients who were treated with anticoagulant therapy for

Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

Science.gov (United States)

Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

2018-01-01

Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

Science.gov (United States)

Kang, Jieun; Kim, Seon Ok; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Jae Seung

2018-05-17

Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

The Effects of High Level Magnesium Dialysis/Substitution Fluid on Magnesium Homeostasis under Regional Citrate Anticoagulation in Critically Ill.

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Mychajlo Zakharchenko

Full Text Available The requirements for magnesium (Mg supplementation increase under regional citrate anticoagulation (RCA because citrate acts by chelation of bivalent cations within the blood circuit. The level of magnesium in commercially available fluids for continuous renal replacement therapy (CRRT may not be sufficient to prevent hypomagnesemia.Patients (n = 45 on CRRT (2,000 ml/h, blood flow (Qb 100 ml/min with RCA modality (4% trisodium citrate using calcium free fluid with 0.75 mmol/l of Mg with additional magnesium substitution were observed after switch to the calcium-free fluid with magnesium concentration of 1.50 mmol/l (n = 42 and no extra magnesium replenishment. All patients had renal indications for CRRT, were treated with the same devices, filters and the same postfilter ionized calcium endpoint (<0.4 mmol/l of prefilter citrate dosage. Under the high level Mg fluid the Qb, dosages of citrate and CRRT were consequently escalated in 9h steps to test various settings.Median balance of Mg was -0.91 (-1.18 to -0.53 mmol/h with Mg 0.75 mmol/l and 0.2 (0.06-0.35 mmol/h when fluid with Mg 1.50 mmol/l was used. It was close to zero (0.02 (-0.12-0.18 mmol/h with higher blood flow and dosage of citrate, increased again to 0.15 (-0.11-0.25 mmol/h with 3,000 ml/h of high magnesium containing fluid (p<0.001. The arterial levels of Mg were mildly increased after the change for high level magnesium containing fluid (p<0.01.Compared to ordinary dialysis fluid the mildly hypermagnesemic fluid provided even balances and adequate levels within ordinary configurations of CRRT with RCA and without a need for extra magnesium replenishment.ClinicalTrials.gov Identifier: NCT01361581.

Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

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Tommaso Sacquegna

2015-12-01

Full Text Available Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF, with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (i.e., dabigatran and direct factor Xa inhibitors (i.e., apixaban and rivaroxaban have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

Direct anticoagulants and nursing: an approach from patient's safety.

Science.gov (United States)

Romero Ruiz, Adolfo; Romero-Arana, Adolfo; Gómez-Salgado, Juan

In recent years, a new line of treatment for the prevention of stroke in non-valvular atrial fibrillation, the so-called direct anticoagulants or new anticoagulants has appeared. The proper management and follow-up of these patients is essential to minimize their side effects and ensure patient safety. In this article, a description of these drugs is given, analyzing their characteristics, functioning and interactions together with the most habitual nursing interventions, as well as a reflection on the implications for the practice. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride.

Science.gov (United States)

Horns, W H; Rado, M; Goldstein, A

1975-06-01

Plasma methadone levels, symptom complaints, and urine tests for illicit opiate use were followed weekly in 17 patients on a methadone maintenance program. There were very large differences between patients in the plasma level established at a given dosage, implying large differences in the rate of methadone metabolism. Despite virtually constant daily dosage, the plasma methadone levels fluctuated greatly from week to week and from day to day in individual patients. With rate exceptions there was no relationship between plasma methadone level and symptom complaints or between weekly chamges in plasma methadone level and changes in symptom complaints. Except possible to identify the ocassional patient with unusually low plasam methadone levels, the determination of methadone levels is not likely to be or practical value in methadone programs.

Isolation and characterization of anticoagulant compound from ...

African Journals Online (AJOL)

GIS

2013-10-02

Oct 2, 2013 ... The structural characterization of anticoagulant GAG was analyzed by Fourier transform infrared ... for pharmaceutical use are currently not available. However ... methods and sold live in the market for human consump- tion.

Anticoagulation in adults with congenital heart disease

DEFF Research Database (Denmark)

Jensen, A S; Idorn, L; Nørager, B

2015-01-01

Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events....... Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable....... It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts...

[Seronegative antiphospholipid syndrome, catastrophic syndrome, new anticoagulants: learning from a difficult case report].

Science.gov (United States)

Joalland, F; de Boysson, H; Darnige, L; Johnson, A; Jeanjean, C; Cheze, S; Augustin, A; Auzary, C; Geffray, L

2014-11-01

The diagnosis of the antiphospholipid syndrome (APS) is based on clinical and biological criteria including the persistent presence of antiphospholipid antibodies and thrombotic events or pregnancy morbidity. Heparins relayed by vitamin K antagonists (VKA) are the gold standard treatment for thrombosis. We report a 17-year-old man who presented with an initially seronegative antiphospholipid syndrome, in whom the diagnosis was late, only obtained after anticoagulation withdrawing, when a catastrophic antiphospholipid syndrome (CAPS) with cutaneous lesions and disseminated intravascular coagulation syndrome occurred. For personal convenience, this patient was initially treated with fondaparinux followed by a new oral anticoagulant (rivaroxaban) before to return to the conventional VKA treatment. The "seronegative" APS is a controversial concept reflecting the heterogeneity of antigenic targets for aPL. This diagnosis may be considered after a rigorous work-up, with the help of haemostasis laboratories testing new emerging aPL assays. In APS, the new anticoagulants represent an attractive option needing nevertheless prospective studies to evaluate their safety and efficacy. Lupus anticoagulant detection in patients treated by new oral anticoagulants is not easy by usually recommended coagulation tests. Copyright © 2014. Published by Elsevier SAS.

Control of anticoagulant therapy and quality of life of patients with atrial fibrillation (review

Directory of Open Access Journals (Sweden)

Shvarts Y.G.

2012-06-01

Full Text Available The review presents the published data on the relevance of the problem of thromboembolic complications in atrial fibrillation, the peculiarities of anticoagulant therapy for this disease. The relationship of clinical characteristics of patients with anticoagulant dose adjustment algorithms has been described. The problem of ethical issues of out of clinical trials patients and the dynamics of their quality of life against the background of long-term use of anticoagulant have been considered.

Does novel oral anticoagulant improve anticoagulation for non-valvular atrial fibrillation associated stroke: An inpatient registration study in Shanghai

Directory of Open Access Journals (Sweden)

Feng-Di Liu

2015-12-01

Full Text Available Abstracts: Objective: To summarize the use rate, safety, efficacy of antithrombotics in stroke/transient ischemic attack (TIA prevention, and reasons for not using dabigatran etexilate (DE in Shanghai, China. Methods: Non-valvular atrial fibrillation (NVAF-associated stroke patients were prospectively registered as an electronic database. Use rate of antithrombotics and reasons for not using DE were extracted during follow-up. Patients' baseline characteristics, recurrent ischemic stroke/TIA events and bleeding complications were analyzed. Patients: From April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h Holter and echocardiography. Results: Before introduction of DE (April 2013, use rates of warfarin and antiplatelets were 28.9% (11/38 and 60.5% (23/38 respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8% (15/72, 12.5% (9/72, and 43.1% (31/72. The DE did not improve use of anticoagulants (P = 0.639. There were 19 (17.3% recurrent ischemic stroke events up to October 2015; two (9.5% in the non-user group, 10 (18.5% in the antiplatelet group, and seven (20.0% in the anticoagulants group (P = 0.570. Furthermore, recurrence rates were similar between the DE group (20.0% and the Warfarin group (20.0%, P = 1.000. The most common reason for not using DE was financial concerns (61.0%, followed by inconvenience to purchase (14.0% and hemorrhage concerns (11.0%. Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs. No bleeding event occurred in the other groups. Only one patient had side effects (dyspepsia and gastroesophageal reflux from DE. Conclusion: The use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance. Keywords

Spontaneous pharyngo-laryngeal hematoma and anticoagulation. A case report

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Marleny CASASOLA-GIRÓN

2016-03-01

Full Text Available Introduction and Objective: Spontaneous pharyngeal-laryngeal hematoma shows the importance of a complete ENT examination in the face of symptoms of banal appearance and a correct history that, in the case reported, unveiled the therapeutic use of anticoagulants. Case description: A 55 year old woman comes to emergency because of unexplained dysphagia. The inspection shows the presence of a hematoma in the pharyngeal-laryngeal region that, after the anticoagulant therapy was reversed, evolved favorably with conservative treatment. Discussion: In this case, apart from medical management performed by the hematology department, we focus our therapeutic approach in the protection of the airway and the prevention of a possible massive bleeding. Determining which patients require endotracheal intubation or tracheostomy and hemostatic surgery is the key to treatment. Conclusions: The anticoagulant therapy involves several complications that ENT specialists must consider in the face of clinical symptoms of dysphagia, dysphonia, dyspnea or signs of bleeding and they must know the possibilities of performance depending on the severity of each case.

Anticoagulant and antimicrobial finishing of non-woven polypropylene textiles

International Nuclear Information System (INIS)

Degoutin, S; Jimenez, M; Casetta, M; Bellayer, S; Chai, F; Blanchemain, N; Neut, C; Kacem, I; Traisnel, M; Martel, B

2012-01-01

The aim of this work is to prepare non-woven polypropylene (PP) textile functionalized with bioactive molecules in order to improve its anticoagulation and antibacterial properties. This paper describes the optimization of the grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated PP, the characterization of the modified substrates and the effect of these modifications on the in vitro biological response towards cells. Then, the immobilization of gentamicin (aminoglycoside antibiotic) and heparin (anticoagulation agent) has been carried out on the grafted samples by either ionic interactions or covalent linkages. Their bioactivity has been investigated and related to the nature of their interactions with the substrate. For gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction of 99% of the adhesion of Escherichia coli have been observed when gentamicin was linked by ionic interactions, allowing the release of the antibiotic. By contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the anticoagulant effect up to 35 min has been highlighted when heparin was covalently bonded on the substrate, by contact with the blood drop. (paper)

A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

Science.gov (United States)

Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

2012-10-05

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation.

Science.gov (United States)

Patel, Aarti A; Lennert, Barb; Macomson, Brian; Nelson, Winnie W; Owens, Gary M; Mody, Samir H; Schein, Jeff

2012-07-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF are at an increased risk for stroke. Thromboprophylaxis with vitamin K antagonists reduces the annual incidence of stroke by approximately 60%, but appropriate thromboprophylaxis is prescribed for only approximately 50% of eligible patients. Health plans may help to improve quality of care for patients with AF by analyzing claims data for care improvement opportunities. To analyze pharmacy and medical claims data from a large integrated commercial database to determine the risk for stroke and the appropriateness of anticoagulant use based on guideline recommendations for patients with AF. This descriptive, retrospective claims data analysis used the Anticoagulant Quality Improvement Analyzer software, which was designed to analyze health plan data. The data for this study were obtained from a 10% randomly selected sample from the PharMetrics Integrated Database. This 10% sample resulted in almost 26,000 patients with AF who met the inclusion criteria for this study. Patients with a new or existing diagnosis of AF between July 2008 and June 2010 who were aged ≥18 years were included in this analysis. The follow-up period was 1 year. Demographics, stroke risk level (CHADS2 and CHA2DS2-VASc scores), anticoagulant use, and inpatient stroke hospitalizations were analyzed through the analyzer software. Of the 25,710 patients with AF (CHADS2 score 0-6) who were eligible to be included in this study, 9093 (35%) received vitamin K antagonists and 16,617 (65%) did not receive any anticoagulant. Of the patients at high risk for stroke, as predicted by CHADS2, 39% received an anticoagulant medication. The rates of patients receiving anticoagulant medication varied by age-group-16% of patients aged <65 years, 22% of those aged 65 to 74 years, and 61% of elderly ≥75 years. Among patients hospitalized for stroke, only 28% were treated with an anticoagulant agent in the outpatient

Unexpected disappearance of portal cavernoma on long-term anticoagulation.

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Silva-Junior, Gilberto; Turon, Fanny; Hernandez-Gea, Virginia; Darnell, Anna; García-Criado, Ángeles; García-Pagán, Juan Carlos

2014-08-01

Idiopathic non-cirrhotic portal hypertension is a rare disease of unknown etiology. Patients with idiopathic non-cirrhotic portal hypertension have an increased risk of developing portal vein thrombosis and this is especially prevalent when HIV is also present. We describe a unique case of a patient with idiopathic non-cirrhotic portal hypertension associated to HIV, who developed acute portal vein thrombosis that despite anticoagulation transformed in portal cavernoma and disappeared completely after five years of follow-up on continuous anticoagulation. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hematology of Nile tilapia (Oreochromis niloticus subjected to anesthesia and anticoagulation protocols

Directory of Open Access Journals (Sweden)

Nadia Cristine Weinert

2015-12-01

Full Text Available Clinical hematology facilitates the diagnosis of disease and can act as a prognostic indicator of pathological conditions in fish. The aim of the present study was to evaluate hematological parameters of Nile tilapia (Oreochromis niloticus subjected to different anesthetics and anticoagulants. Thirty apparently healthy fishes (average weight of 473 ± 35. 50 g and mean total length of 29. 33 ± 0. 37 cm, were selected from the local commercial fish farm in the Lages municipality (Santa Catarina, Brazil. The animals were randomly divided into three groups of 10. In two groups, anesthesia was induced with eugenol (70 mg·L- 1 (EG and Benzocaine hydrochloride (100 mg·L-1 (BG, respectively. Anesthesia was not administered to fish of the third group (CG/control group. Blood samples were obtained by venipuncture of the caudal vessels and placed into microtubes containing sodium heparin or Na2EDTA for further analysis. The results were analyzed by Sigma Stat for Windows, the paired t-test for significant differences between anticoagulants of the same group, and analysis of variance followed by the Tukey test for comparison of means between groups (p ? 0. 05. Most of the observed changes in the erythrogram were significantly higher for the anticoagulant heparin and benzocaine group in comparison to the control group. However, the values obtained for the leukogram were significantly higher for all groups subjected to the Na2EDTA anticoagulant, suggesting that heparin may cause cell clumping. The results suggest that the anesthetics under investigation effectively minimizes the effects of stress caused by handling and invasive procedures, and that the anticoagulant heparin causes less hemolysis in comparison to Na2EDTA for Nile tilapia. Thus, the hematological variations attributed to different anesthetic protocols and/or different anticoagulants should be considered for the species Oreochromis niloticus.

Direct oral anticoagulants: what can we learn?

Science.gov (United States)

Marongiu, Francesco; Barcellona, Doris

2018-03-02

Direct oral anticoagulants (DOACs) represent an innovation because they avoid periodic laboratory monitoring, and also reduce cerebral bleeding. An examination of the performance of DOACs versus warfarin in randomized clinical trials dedicated to atrial fibrillation would reveal the poor performance of warfarin because the percentage of major bleeding is always above 3%; however, the percentage of major bleeding is less than half of that when the management is done in anticoagulation clinics (ACs). Several years ago, a common opinion was that ACs would disappear as soon as DOACs enter the market. We proposed then that ACs could be transformed into thrombosis centres (TCs) because we envisaged many new activities in terms of diagnostic tools and therapeutic choices. After the introduction of DOACs, the role of the ACs has been re-evaluated because their role may be crucial in selecting both the most appropriate diagnostic approach and the best therapeutic option (including anti-vitamin K drugs) for the single patient. TCs can organize a regular follow-up to improve patient adherence to DOACs. Marketing might have a role in the decision making of the single doctor. Efforts should be made for limiting the relationships between doctors and pharmaceutical companies. It seems reasonable to better prepare doctors, during their university courses, for them to develop a greater scientific culture that would enable them to critically read clinical studies and acquire an independent opinion. Ideally, an expert in haemostasis and thrombosis should handle new and old anticoagulants.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

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Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Lupus anticoagulants: first French interlaboratory Etalonorme survey.

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Roussi, J; Roisin, J P; Goguel, A

1996-06-01

In 1994, the, French National Quality Control Group for Hematology, Etalonorme, conducted a large-scale interlaboratory survey concerning the detection of lupus anticoagulants (LA) involving all the 4,500 French laboratories. Each laboratory received the same batch of a lyophilized citrated plasma (94B3) prepared from a patient with LA that had been confirmed by all the techniques used in the intralaboratory study. In the interlaboratory survey, the screening test was activated partial thromboplastin time (APTT); mean APTT calculated from the results reported by 4,029 labs was prolonged (clotting ratio = 1.44) with a large dispersion (coefficients of variation = 18.8%). APTT of the mixture 94B3 + normal plasma were performed by 2,698 laboratories. No correction of APTT was obtained (R = 1.36, Rosner index = 24) with a wide variation between reagents (17 kaolin. This survey allowed Etalonorme to inform French biologists and draft an educational program for the biologic detection of LA and the identification of its mechanism of action.

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

Science.gov (United States)

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist

Recent developments in separation of low molecular weight heparin anticoagulants.

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Sadowski, Radosław; Gadzała-Kopciuch, Renata; Buszewski, Bogusław

2017-10-05

The general function of anticoagulants is to prevent blood clotting and growing of the existing clots in blood vessels. In recent years, there has been a significant improvement in developing methods of prevention as well as pharmacologic and surgical treatment of thrombosis. For over the last two decades, low molecular weight heparins (LMWHs) have found their application in the antithrombotic diseases treatment. These types of drugs are widely used in clinical therapy. Despite the biological and medical importance of LMWHs, they have not been completely characterized in terms of their chemical structure. Due to both, the structural complexity of these anticoagulants and the presence of impurities, their structural characterization requires the employment of advanced analytical techniques. Since separation techniques play the key role in these endeavors, this review will focus on the presentation of recent developments in the separation of LMWH anticoagulants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Subdural hematoma and oral anticoagulant therapy

NARCIS (Netherlands)

Wintzen, A. R.; Tijssen, J. G.

1982-01-01

In a retrospective study of the period 1959 to 1978, the role of anticoagulant therapy (ACT) in the development of subdural hematoma (SH) was investigated. Of 212 cases, 46 were receiving ACT, a proportion highly in excess of the frequency of ACT in the general population of the Leiden area. In this

Evaluation of Oral Anticoagulant-Associated Intracranial Parenchymal Hematomas Using CT Findings.

Science.gov (United States)

Gökçe, E; Beyhan, M; Acu, B

2015-06-01

Intracranial hemorrhage (ICH) is one of the most serious and lethal complications of anticoagulants with a reported incidence of 5-18.5 %. Computed tomographic (CT) findings, should be carefully studied because early diagnosis and treatment of oral anticoagulant use-associated hematomas are vitally important. In the present study, CT findings of intraparenchymal hematomas associated with anticoagulant and antihypertensive use are presented. This study included 45 patients (25 men, 20 women) under anticoagulant (21 patients) or antihypertensive (24 patients) treatment who had brain CT examinations due to complaints and findings suggesting cerebrovascular disease during July 2010-October 2013 period. CT examinations were performed to determine hematoma volumes and presence of swirl sign, hematocrit effect, mid-line shift effect, and intraventricular extension. The patients were 40-89 years of age. In four cases, a total of 51 intraparenchymal hematomas (42 cerebral, 7 cerebellar and 2 brain stem) were detected in multiple foci. Hematoma volumes varied from 0.09 to 284.00 ml. Swirl sign was observed in 87.5 and 63.0 % of OAC-associated ICHs and non-OAC-associated ICHs, respectively. In addition, hematocrit effect was observed in 41.6 % of OAC-associated and in 3.7 % of non-OAC-associated ICHs. Volume increases were observed in all 19 hematomas where swirl sign was detected, and follow-up CT scanning was conducted. Mortality of OAC-associated ICHs was correlated with initial volumes of hematoma, mid-line shift amount, and intraventricular extension. Detection of hematocrit effect by CT scanning of intracranial hematomas should be cautionary in oral anticoagulant use, while detection of swirl sign should be suggestive of active hemorrhage.

[Use of non-vitamin K antagonist oral anticoagulants in Primary Care: ACTUA study].

Science.gov (United States)

Barrios, V; Escobar, C; Lobos, J M; Polo, J; Vargas, D

2017-10-01

Approximately 40% of patients with non-valvular auricular fibrillation (NVAF) who receive vitamin K antagonists (VKA) in Primary Care in Spain have poor anticoagulation control. The objective of the study Actuación en antiCoagulación, Tratamiento y Uso de anticoagulantes orales de acción directa (ACOD) en Atención primaria (ACTUA) (Action in Coagulation, Treatment and Use of direct oral anticoagulants [DOACs]) in Primary Care) was to analyse the current situation regarding the use of VKA and non-vitamin K antagonist oral anticoagulants (NOACs) in patients with NVAF in Primary Care in Spain and the possible issues arising from it. An online survey was created covering various aspects of the use of oral anticoagulants in NAFV. A two-round modified Delphi approach was used. Results were compiled as a set of practical guidelines. Forty-four experts responded to the survey. Consensus was reached in 62% (37/60) of the items. Experts concluded that a considerable number of patients with NVAF who receive VKA do not have a well-controlled INR and that a substantial group of patients who could benefit from being treated with NOACs do not receive them. The use of NOACs increases the probability of having good anticoagulation control and decreases the risk of severe and intracranial haemorrhage. Current limitations to the use of NOACs include administrative barriers, insufficient knowledge about the benefits and risks of NOACs, limited experience of doctors in using them, and their price. Renal insufficiency influences the choice of a particular anticoagulant. The ACTUA study highlights the existing controversies about the use of oral anticoagulants for the treatment of NVAF in Primary Care in Spain, and provides consensus recommendations that may help to improve the use of these medications. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Improvement in long-term ECMO by detailed monitoring of anticoagulation: a case report.

Science.gov (United States)

Sievert, Alicia; Uber, Walter; Laws, Stacey; Cochran, Joel

2011-01-01

The use of unfractionated heparin (UFH) as an anticoagulant during long-term extracorporeal support presents a unique challenge for the clinician in balancing the amount of anticoagulant to maintain adequate anticoagulation without causing excessive bleeding. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) are the most common modality to monitor UFH on extracorporeal membrane oxygenation (ECMO). Limitations to these tests include consumptive coagulopathies, clotting factor deficiencies, platelet dysfunction, and fibrinolysis. The following case report describes the use of alternative monitoring strategies to assess more accurately anticoagulation during ECMO. A 20-month-old female presented to the emergency department with a 5-6 day history of cough, fever, tachypnea, and respiratory distress. She was diagnosed with influenza A and B with pneumonia. The patient was placed on veno-venous ECMO (V-V ECMO) after mechanical ventilation failed. On ECMO day eight, the patient developed a thrombus in her inferior vena cava and pleural effusions, obstructing cannula flow. Laboratory tests revealed the ACT was within range, yet the aPTT was dropping, despite increased heparin. Heparin levels were low and antithrombin-III (AT) concentrations were 40%. Recombinant AT was given and subsequent aPTTs were within the therapeutic range. Later, the aPTT decreased to 475 mg/ dL, and Factor VIII >150 IU/dL, suggesting an acute phase reaction or ongoing systemic inflammation, increasing the risk for thrombosis. We maintained heparin assays between 0.5-0.7 IU/mL and AT >60% to assure heparin's effect. The patient showed no signs of excess bleeding, blood product administration, or clots in the circuit, suggesting proper anticoagulation. The patient was successfully weaned on day 33 and is currently alive and at home. Monitoring of anti-Xa UFH and AT proved effective for measuring anticoagulation and detecting inconsistencies in other anticoagulation

Comparative risk assessment of the first-generation anticoagulant rodenticide diphacinone to raptors

Science.gov (United States)

Rattner, Barnett A.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Horak, Katherine E.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Meteyer, Carol U.; Johnson, John J.

2012-01-01

New regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides in the United States, and in some situations this action may be offset by expanded use of first-generation compounds. We have recently conducted several studies with captive adult American kestrels and eastern screech-owls examining the toxicity of diphacinone (DPN) using both acute oral and short-term dietary exposure regimens. Diphacinone evoked overt signs of intoxication and lethality in these raptors at exposure doses that were 20 to 30 times lower than reported for traditionally used wildlife test species (mallard and northern bobwhite). Sublethal exposure of kestrels and owls resulted in prolonged clotting time, reduced hematocrit, and/or gross and histological evidence of hemorrhage at daily doses as low as 0.16 mg DPN/kg body weight. Findings also demonstrated that DPN was far more potent in short-term 7-day dietary studies than in single-day acute oral exposure studies. Incorporating these kestrel and owl data into deterministic and probabilistic risk assessments indicated that the risks associated with DPN exposure for raptors are far greater than predicted in analyses using data from mallards and bobwhite. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Statement on the safety of glucosamine for patients receiving coumarin anticoagulants

DEFF Research Database (Denmark)

Tetens, Inge

2011-01-01

The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products, Nutrition and Allergies to provide a scientific statement on the safety of glucosamine for patients receiving coumarin anticoagulants. More than 40 case reports have been collected by drug-monitoring agencies...... cases haemorrhage occurred in a variety of organs, and in one case this resulted in a persistent vegetative state. The evidence for an interaction between glucosamine and coumarin anticoagulants is strengthened by the observation that in the majority of cases the INR began to fall to normal values when...... glucosamine intake was discontinued. There is insufficient information to conclude on a mechanism for an interaction between glucosamine and coumarin anticoagulants. There are also insufficient data in the case reports to derive a dose-response relationship for glucosamine and to assess the level of risk...

Oral anticoagulants for stroke prevention in atrial fibrillation.

Science.gov (United States)

Senoo, Keitaro; Lane, Deirdre A; Lip, Gregory Y H

2014-09-01

The availability of 4 non-vitamin K oral anticoagulants (NOACs), that is, dabigatran, rivaroxaban, apixaban, and edoxaban, has changed the landscape of stroke prevention in patients with atrial fibrillation. This review article provides an overview of the 4 phase III studies that have compared these NOACs, examining major outcomes of efficacy and safety. A range of practical questions relating to the NOACs have emerged, including topics such as patient selection, treating patients with renal impairment, treating elderly patients, and combining anticoagulant therapy with antiplatelet drugs. We also address the interaction of various patient characteristics with the treatments and suggest the features can assist the physician in the choice of a particular NOAC for a particular patient(s). Copyright © 2014 Elsevier B.V. All rights reserved.

Transportation cost of anticoagulation clinic visits in an urban setting.

Science.gov (United States)

Hwang, Jamie M; Clemente, Jennifer; Sharma, Krishna P; Taylor, Thomas N; Garwood, Candice L

2011-10-01

Patients being managed on warfarin make frequent or regular visits to anticoagulation monitoring appointments. International studies have evaluated transportation cost and associated time related to anticoagulation clinic visits. To our knowledge, no studies have evaluated the cost of transportation to such clinic visits in the United States. To describe the methods of transportation and estimate the average total cost of transportation to and from an anticoagulation clinic in an urban setting. We prospectively conducted a survey of patients treated at the Harper Anticoagulation Clinic located in Detroit, Michigan, during November 2010. The survey was given to patients while waiting at their regularly scheduled clinic appointments and included questions regarding mode of transportation, distance traveled in miles, parking payment, and time missed from work for clinic appointments. The mean distance traveled was translated into cost assuming 50 cents per mile based on 2010 estimates by the Internal Revenue Service. Sixty patients responded to the 11-item survey; response rates for individual items varied because participants were instructed to skip questions that did not pertain to them. Of the 47 participants responding to demographic questions, 70.2% were female, and 46.8% were older than 60 years. Transportation by private vehicle (80.0%), either driven by patients (41.7%) or someone else (38.3%), was the most common method reported. Use of private automobile translated into a cost of $11.19 per round trip. Other means of transportation identified include a ride from a medical transportation service (10.0%), bus (5.0%), walking (3.3%), and taxi (1.7%). The mean (SD) distance traveled to the clinic for all methods of transportation was 8.34 (7.7) miles. We estimated the average cost of round-trip transportation to be $10.78 weighted for all transportation modes. This is a direct nonmedical cost that is paid for by most patients out of pocket. However, 9 of 44 (20

Real life anticoagulation treatment of patients with atrial fibrillation in Germany

DEFF Research Database (Denmark)

Wilke, Thomas; Groth, Antje; Pfannkuche, Matthias

2015-01-01

Oral anticoagulation (OAC) with either new oral anticoagulants (NOACs) or Vitamin-K antagonists (VKAs) is recommended by guidelines for patients with atrial fibrillation (AF) and a moderate to high risk of stroke. Based on a claims-based data set the aim of this study was to quantify the stroke-r...... that both patient/disease characteristics and treatment environment/general prescribing behaviour of physicians may explain the OAC under-use in AF patients....

Non arteritic anterior ischemic optic neuropathy; does anticoagulation help?

International Nuclear Information System (INIS)

Aftab, A.M.; Iqbal, M.; Ali, A.; Rauf, A.

2017-01-01

Non Arteritic Anterior Ischemic Optic Neuropathy (NAION) is the most common acute optic neuropathy in patients over 50 years of age. This study was conducted to determine the beneficial effects of anticoagulation with Heparin and Warfarin in patients with NAION presenting within 4 weeks of onset of symptoms Methods: A prospective, interventional, pilot study was conducted in Eye- A unit of Khyber Teaching Hospital from July 2010 onwards on patients with NAION presenting within 4 weeks of onset of symptoms. Patients underwent complete ophthalmological examination including Snellen's visual acuity (latter converted to Log MAR), pupil examination, fundus examination and automated Humphrey visual field analysis. Hematologic tests, Thrombophilia screening, Echocardiography and carotid Doppler ultrasound were carried on patients. All patients were anticoagulated with Heparin and Warfarin after obtaining informed written consent. Patients were examined at 1 Month, 3 months and 6 months' time period. Primary parameter measured was improvement in visual acuity. Results: Total number of patients in our study was 24. Regarding visual outcome total number of patients having significant improvement of visual acuity in our study was 16 (66.6 percent), while 4 (16.7 percent) patients had marginal improvement of visual acuity. Three (12.5 percent) patients maintained stable visual acuity of 6/6 throughout the study period in presence of thrombophilic disorders. One patient (4.1 percent) suffered a decline in visual acuity compared to VA at baseline presentation. Conclusions: Anticoagulation using heparin and warfarin does benefit patients with NAION presenting within 4 weeks of onset of symptoms. In our study a higher proportion of patients experienced significant improvement of visual acuity following anticoagulation as compared to the highest reported spontaneous improvement in such patients. (author)

Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

Science.gov (United States)

LaBonte, Michelle L

2014-09-01

Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Prevalence of Lupus Anticoagulant in Women with Spontaneous ...

African Journals Online (AJOL)

2017-10-26

Oct 26, 2017 ... ... pregnancy. Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, ... pregnancy outcomes such as preeclampsia/eclampsia and small for date deliveries. ... changes in a background of APL syndrome.

Are pharmacological properties of anticoagulants reflected in pharmaceutical pricing and reimbursement policy? Out-patient treatment of venous thromboembolism and utilization of anticoagulants in Poland.

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Bochenek, T; Czarnogorski, M; Nizankowski, R; Pilc, A

2014-06-01

Pharmacotherapy with vitamin K antagonists (VKA) and low-molecular-weight heparins (LMWH) is a major cost driver in the treatment of venous thromboembolism (VTE). Major representatives of anticoagulants in Europe include: acenocoumarol and warfarin (VKA), enoxaparin, dalteparin, nadroparin, reviparin, parnaparin and bemiparin (LMWH). Aim of this report is to measure and critically assess the utilization of anticoagulants and other resources used in the out-patient treatment of VTE in Poland. To confront the findings with available scientific evidence on pharmacological and clinical properties of anticoagulants. The perspectives of the National Health Fund (NHF) and the patients were adopted, descriptive statistics methods were used. The data were gathered at the NHF and the clinic specialized in treatment of coagulation disorders. Non-pharmacological costs of treatment were for the NHF 1.6 times higher with VKA than with LMWH. Daily cost of pharmacotherapy with LMWH turned out higher than with VKA (234 times for the NHF, 42 times per patient). Within both LMWH and VKA the reimbursement due for the daily doses of a particular medication altered in the manner inversely proportional to the level of patient co-payment. Utilization of long-marketed and cheap VKA was dominated by LMWH, when assessed both through the monetary measures and by the actual volume of sales. Pharmaceutical reimbursement policy favored the more expensive equivalents among VKA and LMWH, whereas in the financial terms the patients were far better off when remaining on a more expensive alternative. The pharmaceutical pricing and reimbursement policy of the state should be more closely related to the pharmacological properties of anticoagulants.

Treatment Changes among Users of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation

DEFF Research Database (Denmark)

Poulsen, Maja Hellfritzsch; Husted, Steen Elkjær; Grove, Erik Lerkevang

2017-01-01

Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on ...

Antiplatelet and Anticoagulant Drugs in Interventional Radiology

International Nuclear Information System (INIS)

Altenburg, Alexander; Haage, Patrick

2012-01-01

In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

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Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

A cost-analysis model for anticoagulant treatment in the hospital setting.

Science.gov (United States)

Mody, Samir H; Huynh, Lynn; Zhuo, Daisy Y; Tran, Kevin N; Lefebvre, Patrick; Bookhart, Brahim

2014-07-01

Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations. An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature. Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups. The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received. From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with

The Need for Anticoagulation Following Inferior Vena Cava Filter Placement: Systematic Review

International Nuclear Information System (INIS)

Ray, Charles E.; Prochazka, Allan

2008-01-01

Purpose. To perform a systemic review to determine the effect of anticoagulation on the rates of venous thromboembolism (pulmonary embolus, deep venous thrombosis, inferior vena cava (IVC) filter thrombosis) following placement of an IVC filter. Methods. A comprehensive computerized literature search was performed to identify relevant articles. Data were abstracted by two reviewers. Studies were included if it could be determined whether or not subjects received anticoagulation following filter placement, and if follow-up data were presented. A meta-analysis of patients from all included studies was performed. A total of 14 articles were included in the final analysis, but the data from only nine articles could be used in the meta-analysis; five studies were excluded because they did not present raw data which could be analyzed in the meta-analysis. A total of 1,369 subjects were included in the final meta-analysis. Results. The summary odds ratio for the effect of anticoagulation on venous thromboembolism rates following filter deployment was 0.639 (95% CI 0.351 to 1.159, p = 0.141). There was significant heterogeneity in the results from different studies [Q statistic of 15.95 (p = 0.043)]. Following the meta-analysis, there was a trend toward decreased venous thromboembolism rates in patients with post-filter anticoagulation (12.3% vs. 15.8%), but the result failed to reach statistical significance. Conclusion. Inferior vena cava filters can be placed in patients who cannot receive concomitant anticoagulation without placing them at significantly higher risk of development of venous thromboembolism

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study.

Science.gov (United States)

Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D

2017-05-01

To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Could Some Geriatric Characteristics Hinder the Prescription of Anticoagulants in Atrial Fibrillation in the Elderly?

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Paule Denoël

2014-01-01

Full Text Available Several studies have reported underprescription of anticoagulants in atrial fibrillation (AF. We conducted an observational study on 142 out of a total of 995 consecutive ≥75 years old patients presenting AF (14% when admitted in an emergency unit of a general hospital, in search of geriatric characteristics that might be associated with the underprescription of anticoagulation therapy (mostly antivitamin K at the time of the study. The following data was collected from patients presenting AF: medical history including treatment and comorbidities, CHADS2 score, ISAR scale (frailty, Lawton’s scale (ADL, GDS scale (mood status, MUST (nutrition, and blood analysis (INR, kidney function, and albumin. Among those patients for who anticoagulation treatment was recommended (73%, only 61% were treated with it. In the group with anticoagulation therapy, the following characteristics were observed more often than in the group without such therapy: a recent (≤6 months hospitalization and medical treatment including digoxin or based on >3 different drugs. Neither the value of the CHADS2 score, nor the geriatric characteristics could be correlated with the presence or the absence of an anticoagulation therapy. More research is thus required to identify and clarify the relative importance of patient-, physician-, and health care system-related hurdles for the prescription of oral anticoagulation therapy in older patients with AF.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

Science.gov (United States)

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

Reversing the Effect of Oral Anticoagulant Drugs: Established and Newer Options.

Science.gov (United States)

Ansell, Jack E

2016-06-01

The vitamin K antagonists (VKAs) have been the standard (and only) oral anticoagulants used for the long-term treatment or prevention of venous thromboembolism or stroke in patients with atrial fibrillation. The coagulopathy induced by VKAs can be reversed with vitamin K, and in urgent situations, the vitamin K-dependent coagulation factors can be replaced by transfusion. In the last decade, a new class of oral anticoagulants has been developed, direct oral anticoagulants that bind to a specific coagulation factor and neutralize it. These compounds were shown to be effective and safe compared with the VKAs and were licensed for specific indications, but without a specific reversal agent. The absence of a reversal agent is a barrier to more widespread use of these agents. Currently, for the management of major life-threatening bleeding with the direct oral anticoagulants, most authorities recommend the use of four factor prothrombin complex concentrates. There are now three reversal agents in development and poised to enter the market. Idarucizumab is a specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran, which was recently approved for use in the USA. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Ciraparantag is an antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.

Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration.

Science.gov (United States)

Wong, Y M; Quek, Y-N; Tay, J C; Chadachan, V; Lee, H K

2011-10-01

Anticoagulation consultations provided by a pharmacist-staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching hospital in Singapore, pharmacist-managed anticoagulation clinics have been in place since 1997. Pharmacist-managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist-managed inpatient anticoagulation service. This was a single-centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post-implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge. A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004). Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist-managed anticoagulation service. The time to therapeutic INR was

Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

Science.gov (United States)

Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

2015-01-01

Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or

Local hemostatic measures in anticoagulated patients undergoing oral surgery: a systematized literature review

Directory of Open Access Journals (Sweden)

Fábio Wildson Gurgel Costa

2013-01-01

Full Text Available PURPOSE: To conduct a systematized review of the literature about the main local hemostatic measures to control postoperative bleeding in anticoagulated patients. METHODS: A systematized review of literature was performed in the electronic database Medline (PubMed without restriction of the publication date. The eligibility criteria were studies involving maintenance of the anticoagulant therapy, prospective studies, retrospective studies, randomized clinical trials, controlled clinical studies, comparative studies, multicentric studies or case-control studies. Studies discontinuing anticoagulant therapy, case reports, literature reviews, in vitro studies, animal experiments and articles written in language not compatible with the search strategy adopted in this work were excluded. RESULTS: Twenty-four articles that met the adopted eligibility criteria were selected, enrolling 3891 subjects under anticoagulant therapy. A total of 171 cases of hemorrhage was observed. Tranexamic acid was the main local hemostatic measure used to controlling of postoperative bleeding. CONCLUSION: The local hemostatic measures proved to be effective according to previously published studies. Nevertheless, further clinical studies should be conducted to confirm this effectiveness.

SMART: self-management of anticoagulation, a randomised trial [ISRCTN19313375].

Science.gov (United States)

McCahon, Deborah; Fitzmaurice, David A; Murray, Ellen T; Fuller, Christopher J; Hobbs, Richard F D; Allan, Teresa F; Raftery, James P

2003-09-18

Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

SMART: Self-Management of Anticoagulation, a Randomised Trial [ISRCTN19313375

Directory of Open Access Journals (Sweden)

Murray Ellen T

2003-09-01

Full Text Available Abstract Background Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR. The development of reliable near patient testing (NPT systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. Method The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. Discussion The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

Energy Technology Data Exchange (ETDEWEB)

Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Radiology Department (United Kingdom); Shiach, Caroline, E-mail: caroline.shiach@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Haematology Department (United Kingdom)

2017-03-15

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

International Nuclear Information System (INIS)

Kumar, Pradesh; Ravi, Rajeev; Sundar, Gaurav; Shiach, Caroline

2017-01-01

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

Anticoagulation therapy a risk factor for the development of chronic subdural hematoma

DEFF Research Database (Denmark)

Aspegren, Oskar P.; Åstrand, Ramona; Lundgren, Maria I.

2013-01-01

Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy.......Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy....

Bioassay-guided fractionation of Melastoma malabathricum Linn. leaf solid phase extraction fraction and its anticoagulant activity.

Science.gov (United States)

Khoo, Li Teng; Abdullah, Janna Ong; Abas, Faridah; Tohit, Eusni Rahayu Mohd; Hamid, Muhajir

2015-02-24

The aims of this study were to examine the bioactive component(s) responsible for the anticoagulant activity of M. malabathricum Linn. leaf hot water crude extract via bioassay-guided fractionation and to evaluate the effect of bioactive component(s) on the intrinsic blood coagulation pathway. The active anticoagulant fraction of F3 was subjected to a series of chromatographic separation and spectroscopic analyses. Furthermore, the effect of the bioactive component(s) on the intrinsic blood coagulation pathway was studied through immediate and time incubation mixing studies. Through Activated Partial Thromboplastin Time (APTT) assay-guided fractionation, Subfraction B was considered the most potent anticoagulant fraction. Characterisation of Subfraction B indicated that anticoagulant activity could partly be due to the presence of cinnamic acid and a cinnamic acid derivative. APTT assays for both the immediate and time incubation mixing were corrected back into normal clotting time range (35.4-56.3 s). In conclusion, cinnamic acid and cinnamic acid derivative from Subfraction B were the first such compounds to be discovered from M. malabathricum Linn. leaf hot water crude extract that possess anticoagulant activity. This active anticoagulant Subfraction B prolonged blood clotting time by causing factor(s) deficiency in the intrinsic blood coagulation pathway.

Physicochemical properties and anticoagulant activity of polyphenols derived from Lachnum singerianum

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Shuai Zong

2017-10-01

Full Text Available In this study, polyphenols (LSP were obtained from the fermentation broth of Lachnum singerianum. Two fractions were isolated by Sephadex LH-20 chromatographic column, and the primary fraction (LSP-1 was collected. The comprehensive physicochemical properties of phenolic acids and polyhydroxy phenolic compounds of LSP-1 were determined by UV-visible spectroscopy, Fourier transform infrared spectroscopy, and gas chromatography–mass spectrometry. Results of anticoagulant activity assay in vitro showed that LSP-1 could lengthen prothrombin time, activated partial thromboplastin time, and thrombin time of mouse plasma. In addition, anticoagulant activity results in vivo showed that high dose of LSP-1 could significantly prolong bleeding time, coagulation time, prothrombin time, activated partial thromboplastin time, and thrombin time of hypercoagulable mice induced by adrenaline, reduce the content of fibrinogen and enhance antithrombin III activity. All results indicated that the LSP-1 could serve well as an anticoagulant, and might be used as a potential natural drug candidate for thrombosis.

Technology-assisted self-testing and management of oral anticoagulation therapy: a qualitative patient-focused study.

Science.gov (United States)

Kuljis, Jasna; Money, Arthur G; Perry, Mark; Barnett, Julie; Young, Terry

2017-09-01

Oral anticoagulation therapy requires regular blood testing to ensure therapeutic levels are maintained and excessive bleeding/clotting is avoided. Technology-assisted self-testing and management is seen as one of the key areas in which quality of care can be improved whilst reducing costs. Nevertheless, levels of patient engagement in self-testing and management remain low. To date, little research emphasis has been placed on understanding the patients' perspectives for low engagement. The typical approach adopted by healthcare providers is to provide patient education programmes, with the expectation that individual patients will change their behaviour and adopt new self-care strategies. However, if levels of patient engagement are to be increased, healthcare providers must also develop a better understanding of how their clinical service provision is perceived by patients and make adaptations. To explore patient views, needs and expectations of an anticoagulation service and the self-testing and management services provided. Interviews were conducted with 17 patients who currently engage in international normalised ratio (INR) self-testing and management. Thematic coding and analysis were carried out on the interview transcripts. Four high-level themes emerged from interviews: (i) role of clinic, (ii) motivations for self-testing, (iii) managing INR and (iv) trust. The clinic was seen as adding value in terms of specifying testing frequency, dosage profiles and calibrating equipment. Prompt communication from clinic to patient was also valued, although more personalised/real-time communication would help avoid feelings of isolation. Patients felt more in control as self-tester/managers and often took decisions about treatment adjustments themselves. However, some also manipulated their own test results to avoid 'unnecessary' interventions. More personalised/real-time communication, pragmatic and collaborative patient-clinician partnerships and recognition of

Oral anticoagulation for stroke prevention amongst atrial fibrillation patients with valvular heart disease: an update.

Science.gov (United States)

Ha, Andrew C T; Verma, Atul; Verma, Subodh

2017-03-01

The majority of evidence on the safety and efficacy of oral anticoagulation for stroke prevention amongst patients with atrial fibrillation is derived from those without significant valvular heart disease. This article will review current knowledge, areas of uncertainty and controversy, and ongoing research on oral anticoagulation for stroke prevention amongst patients with valvular heart disease. The rates of stroke, systemic embolism, and major bleeding were similar for patients with and without significant native valvular disease when treated with direct oral anticoagulants (DOACs) or vitamin K antagonists. There are very limited prospective data on the safety and efficacy of DOAC use for patients with bioprosthetic valves or rheumatic mitral stenosis. Atrial fibrillation patients with concomitant valvulopathies constitute a group with high thromboembolic risk and should be treated with oral anticoagulation. There is good supportive evidence that DOAC is well tolerated and effective in preventing thromboembolism amongst patients with native valvular disease. Further research is underway to better define the risks and benefits of DOAC use among patients with bioprosthetic valves or rheumatic mitral stenosis in preventing thromboembolic events. Until then, vitamin K antagonists remain the oral anticoagulant of choice for these patient subsets.

INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

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Rose, A J; Berlowitz, D R; Miller, D R; Hylek, E M; Ozonoff, A; Zhao, S; Reisman, J I; Ash, A S

2012-04-01

Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets. © 2012 International Society on Thrombosis and Haemostasis.

Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats:

DEFF Research Database (Denmark)

Markussen, Mette Drude; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

Anticoagulant resistance in Norway rats (Rattus norvegicus) has been suggested to be due to mutations in the VKORC1 gene, encoding the target protein of anticoagulant rodenticides such as warfarin and bromadiolone. Other factors, e.g. pharmacokinetics, may however also contribute to resistance. We...... that bromadiolone resistance in Norway rats involves enhanced anticoagulant clearance and metabolism catalyzed by specific cytochrome P450 enzymes, such as Cyp2e1, Cyp3a2 and Cyp3a3. This pharmacokinetically based resistance varies to some extend between the genders....

Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats

DEFF Research Database (Denmark)

Markussen, Mette Drude Kjær; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

Background: Anticoagulant resistance in Norway rats, Rattus norvegicus (Berk.), has been suggested to be conferred by mutations in the VKORC1 gene, encoding the target protein of anticoagulant rodenticides. Other factors, e.g. pharmacokinetics, may also contribute to resistance, however. To examine......, Cyp3a2 and Cyp3a3 genes. On exposure to bromadiolone, females had higher Cyp2e1 expression than males, which possibly explains why female rats are generally more tolerant to anticoagulants than male rats. Conclusion: results suggest that bromadiolone resistance in a Danish strain of Norway rats...

[Pharmaceutical advice concerning different pharmaceutical dosage forms].

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Szakonyi, Gergely; Zelkó, Romána

2010-01-01

The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

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Gudbjornsson B

2018-05-01

Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

Impact of Anticoagulation in Elderly Patients With Pulmonary Embolism That Undergo IVC Filter Placement: A Retrospective Cohort Study.

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Falatko, John M; Dalal, Bhavinkumar; Qu, Lihua

2017-12-01

Anticoagulation is the primary treatment for pulmonary embolism (PE). Inferior vena cava (IVC) filters are an adjunctive intervention to prevent recurrent pulmonary embolism. Long-term outcomes in elderly patients with contraindications to anticoagulation after IVC filter placement for prevention of recurrent pulmonary embolism have yet to be assessed. Patients ≥60years of age, that had an IVC filter placed between 1 January, 2008 and 2 February, 2013, with a primary diagnosis of pulmonary embolism, were included. Patients that died during index hospitalisation, were discharged to hospice, or had active malignancy were excluded. The primary endpoint was overall survival. Patients were divided depending on whether they were treated with an approved anticoagulant for VTE or had no anticoagulant. Of the 152 patients identified, 55 were not anti-coagulated after IVC filter placement. The incidence of death was 0.4 per 1000 filter days and 0.7 per 1000 filter days in the anti-coagulated and untreated groups respectively (p-value=0.06). After statistical correction for co-morbid conditions, the effect of anticoagulation was not significant (HR 0.82 CI 0.49-1.37, p-value 0.46). Age was a significant confounder that was associated with death. Increased BMI was protective. Indications for IVC filter placement were numerous, but similar between the two groups. Treatment with an approved anticoagulant is recommended after IVC filter placement for prevention of recurrent PE, however its effect may be attenuated by advanced age. In elderly patients that have undergone IVC filter placement for prevention of recurrent PE, survival may be more dependent on age and co-morbid conditions than exposure to anticoagulation. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

[Anticoagulation in the aged patient with atrial fibrillation: What are prescribing cardiologists, geriatricians and general practitioners?].

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Fuchs, P; Vogel, T; Lang, P-O

2015-08-01

To assess prescribing of anticoagulants in atrial fibrillation (AF) in the elderly, both a quantitative point of view (rate of anticoagulation) and qualitative (type of anticoagulation). Determinants of prescribing and non-prescribing were also analysed. Prospective survey of practice, based on one clinical case and questionnaire conducted in 60 practitioners (20 cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]). In reading the clinical case, 88.3% of physicians would have initiated a treatment; three types of treatments would have been chosen: AVK (68.3%), ODA (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to initiate anticoagulation varied according to the specialty. Cardiologists considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; PC: 90.0%, G: 60.0%, MG: 55.0%; PC: 85.0%, G: 55.0%, MG: 60.0%; PC: 80.0%, G: 35.0%, MG: 25.0%; PC: 15.0%, G: 5.0%, MG: 0.0%; PC: 35.0%, G: 5.0%, MG: 45.0%; PC: 70.0%, G: 75.0%, MG: 85.0%; P<0.05). This survey confirms that the FA remains under anticoagulated in the elderly and the barriers to the prescription of oral anticoagulation are often without rational basis. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Quality of Life analysis of patients in chronic use of oral anticoagulant: an observational study

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Almeida Geisa

2011-10-01

Full Text Available Abstract Background Treatment with oral anticoagulant may influence the quality of life perception as it promotes changes in the patient's life, not offering an evident symptomatic relief and presenting well defined risks, such as bleeding. In this trial, the influence of chronic use of anticoagulants on the quality of life perception has been analyzed in patients assisted at the anticoagulation outpatient unit. Methods The health related quality of life was evaluated through a cross-section study with a sample composed of 72 patients seen from July 23, 2009 to September 2, 2010 at the Anticoagulation Outpatient Unit of the Federal University of Bahia's University Hospital. The study's population was composed by patients with atrial fibrillation and mechanical heart valve. The patients were submitted to two quality of life evaluation questionnaires: a generic questionnaire - the Medical Outcomes Study SF-36 Health Survey (SF36 - and a specific questionnaire - the Duke Anticoagulation Satisfaction Scale (DASS. Results The quality of life perception of the patients studied, based on both the DASS and the SF36, was positive regarding the treatment with oral anticoagulant. The SF36 presented an average score of 62.2 (± 20.0. Among the SF36 evaluated domains, the physical-emotional aspect was the most compromised one regarding life quality perception. The DASS presented an average score of 67.1 (± 18.2 and the domain presenting a greater compromise was the one related to the treatment inconveniences (annoyances, burdens and obligations. Previous hemorrhagic event, comorbidities, drug interactions with medicines that increase the anticoagulant effect, lower education level in the SF36 and younger age group influence a more negative perception of the quality of life, whereas lower education level in the DASS and the duration of treatment for more than 1 year offer a more positive perception. Conclusion Patients seen at the anticoagulation outpatient

Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echis Carinatus) Venom

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Amrollahi Byoki, Elham; Zare Mirakabadi, Abbas

2013-01-01

Objective(s): Snake venoms contain complex mixture of proteins with biological activities. Some of these proteins affect blood coagulation and platelet function in different ways. Snake venom toxin may serve as a starting material for drug design to combat several pathophysiological problems such as cardiovascular disorders. In the present study, purification of anticoagulation factor from venom of snake (Echis carinatus) was studied. Materials and Methods: Anticoagulation activity of crude venom, fractions and purified peptide were determined by using prothrombin time (PT) and thrombin time (TT). Three fractions were partially purified from the venom of E. Carinatus by gel filtration on sephadex G-75 and final purification was performed by high-performance liquid chromatography (HPLC) with C18 column. A purified anticoagulant factor was derived which showed a single protein band in SDS-PAGE electrophoresis under reducing condition. Results: Results of PT and TT tests for purified peptide (EC217) were found to be 102±4.242 and < 5 min. respectively. Determination of molecular weight revealed that the active purified peptide (EC217) was about 30 KD. Conclusion: The present study showed that the venom of E. carinatus contains at least one anticoagulant factor. PMID:24494065

Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echis carinatus Venom

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Elham Amrollahi Byoki

2013-11-01

Full Text Available   Objective(s: Snake venoms contain complex mixture of proteins with biological activities. Some of these proteins affect blood coagulation and platelet function in different ways. Snake venom toxin may serve as a starting material for drug design to combat several pathophysiological problems such as cardiovascular disorders. In the present study, purification of anticoagulation factor from venom of snake (Echis carinatus was studied. Anticoagulation activity of crude venom, fractions and purified peptide were determined by using prothrombin time (PT and thrombin time (TT. Three fractions were partially purified from the venom of E. Carinatus by gel filtration on sephadex G-75 and final purification was performed by high-performance liquid chromatography (HPLC with C18 column. A purified anticoagulant factor was derived which showed a single protein band in SDS-PAGE electrophoresis under reducing condition. Results of PT and TT tests for purified peptide (EC217 were found to be 102±4.242 and < 5 min. respectively. Determination of molecular weight revealed that the active purified peptide (EC217 was about 30 KD. In conclusion, the present study showed that the venom of E. carinatus contains at least one anticoagulant factor.

Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

International Nuclear Information System (INIS)

Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

2008-01-01

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

Intelligent system for improving dosage control

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Fabio Cosme Rodrigues dos Santos

2017-02-01

Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action?

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Pereira, Maria G; Benevides, Norma M B; Melo, Marcia R S; Valente, Ana Paula; Melo, Fábio R; Mourão, Paulo A S

2005-09-05

Marine red algae are an abundant source of sulfated galactans with potent anticoagulant activity. However, the specific structural motifs that confer biological activity remain to be elucidated. We have now isolated and purified a sulfated galactan from the marine red alga, Gellidium crinale. The structure of this polysaccharide was determined using NMR spectroscopy. It is composed of the repeating structure -4-alpha-Galp-(1-->3)-beta-Galp1--> but with a variable sulfation pattern. Clearly 15% of the total alpha-units are 2,3-di-sulfated and another 55% are 2-sulfated. No evidence for the occurrence of 3,6-anhydro alpha-galactose units was observed in the NMR spectra. We also compared the anticoagulant activity of this sulfated galactan with a polysaccharide from the species, Botryocladia occidentalis, with a similar saccharide chain but with higher amounts of 2,3-di-sulfated alpha-units. The sulfated galactan from G. crinale has a lower anticoagulant activity on a clotting assay when compared with the polysaccharide from B. occidentalis. When tested in assays using specific proteases and coagulation inhibitors, these two galactans showed significant differences in their activity. They do not differ in thrombin inhibition mediated by antithrombin, but in assays where heparin cofactor II replaces antithrombin, the sulfated galactan from G. crinale requires a significantly higher concentration to achieve the same inhibitory effect as the polysaccharide from B. occidentalis. In contrast, when factor Xa instead of thrombin is used as the target protease, the sulfated galactan from G. crinale is a more potent anticoagulant. These observations suggest that the proportion and/or the distribution of 2,3-di-sulfated alpha-units along the galactan chain may be a critical structural motif to promote the interaction of the protease with specific protease and coagulation inhibitors.

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine

OpenAIRE

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2016-01-01

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity ...

Sulfated modification and anticoagulant activity of pumpkin (Cucurbita pepo, Lady Godiva) polysaccharide.

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Liang, Li; Ao, Le; Ma, Tao; Ni, Yuanying; Liao, Xiaojun; Hu, Xiaosong; Song, Yi

2018-01-01

Sulfated modification of pumpkin polysaccharide using CAS with pyridines as catalysts under different conditions was conducted to obtain different degrees of sulfation on a laboratory scale. Anticoagulant activities of pumpkin polysaccharide and its sulfated derivatives were also investigated employing various established in vitro systems. Results showed that addition of high ratio of CAS/pyridine under constant conditions could increase the degree of substitution. Sulfate substitution was further confirmed by the FT-IR and 13 C NMR analysis. The d f values between 2.11-2.73 indicated the relatively expanded conformation of the sulfated derivatives. The sulfated polysaccharides showed higher anticoagulant activities through activated partial thrombosis time (aPTT), thrombin time (TT), prothrombin time (PT) and anti-Xa activity assay, which revealed that better anticoagulant activities could be obtained when DS remained higher and M w maintained in a moderate range. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study.

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Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R

2016-08-30

Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N = 59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF versus standard care during a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14 ± 4 months of follow-up, 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy versus $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. © 2016 Wiley Periodicals, Inc.

Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on rebleeding and thromboembolism in acute gastrointestinal bleeding.

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Naoyoshi Nagata

Full Text Available Anticoagulant management of acute gastrointestinal bleeding (GIB during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB.Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs and warfarin users.Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users.Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

Science.gov (United States)

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-12-01

Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

Honey Bee Venom (Apis mellifera Contains Anticoagulation Factors and Increases the Blood-clotting Time

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Hossein Zolfagharian

2015-12-01

Full Text Available Objectives: Bee venom (BV is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50, and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Blood samples were obtained from 10 rabbits, and the prothrombin time (PT and the partial thromboplastin time (PTT tests were conducted. The approximate lethal dose (LD values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa, respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2 and melittin, and that can increase the blood clotting times in vitro.

Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

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Patel R

2016-05-01

Full Text Available Raj Patel Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, UK Abstract: Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE. For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. Keywords: venous thromboembolism, oral anticoagulant, prevention, treatment, primary

Evaluation of students' knowledge about paediatric dosage calculations.

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Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

2018-01-01

Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies.

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Galland, Joris; Mohamed, Shirine; Revuz, Sabine; de Maistre, Emmanuel; de Laat, Bas; Marie, Pierre-Yves; Zuily, Stéphane; Lévy, Bruno; Regnault, Véronique; Wahl, Denis

2016-07-01

Lupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant-hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

Science.gov (United States)

Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

2016-06-01

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

New Direct Oral Anticoagulants (DOAC and Their Use Today

Directory of Open Access Journals (Sweden)

Heike Schwarb

2016-03-01

Full Text Available The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC, we now have an alternative to the traditional vitamin K antagonists (VKA for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.

Advances in solid dosage form manufacturing technology.

Science.gov (United States)

Andrews, Gavin P

2007-12-15

Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation.

Aneurysmal subarachnoid hemorrhage in patients taking direct oral anticoagulants: A case series and discussion of management

Directory of Open Access Journals (Sweden)

Joseph H. McMordie, MD

2018-03-01

Full Text Available Direct oral anticoagulants are becoming more commonplace for the treatment of nonvalvular atrial fibrillation and deep vein thrombosis. Unfortunately, effective reversal agents are not widely available limiting options for neurosurgical intervention during active anticoagulation. We report a case series of 3 patients treated for aneurysmal subarachnoid hemorrhage while taking direct oral anticoagulants. All three underwent open surgical clipping after adequate time was allowed for drug metabolism. Decision-making must take into account timing of intervention, drug half-life, and currently available reversal agents.

Dosage sensitivity shapes the evolution of copy-number varied regions.

Directory of Open Access Journals (Sweden)

Benjamin Schuster-Böckler

2010-03-01

Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

Teachers' Perceptions of School Organizational Climate as Predictors of Dosage and Quality of Implementation of a Social-Emotional and Character Development Program.

Science.gov (United States)

Malloy, Margaret; Acock, Alan; DuBois, David L; Vuchinich, Samuel; Silverthorn, Naida; Ji, Peter; Flay, Brian R

2015-11-01

Organizational climate has been proposed as a factor that might influence a school's readiness to successfully implement school-wide prevention programs. The aim of this study was to evaluate the influence of teachers' perceptions of three dimensions of school organizational climate on the dosage and quality of teacher implementation of Positive Action, a social-emotional and character development (SECD) program. The dimensions measured were teachers' perceptions of (a) the school's openness to innovation, (b) the extent to which schools utilize participatory decision-making practices, and (c) the existence of supportive relationships among teachers (teacher-teacher affiliation). Data from 46 teachers in seven schools enrolled in the treatment arm of a longitudinal, cluster-randomized, controlled trial were analyzed. Teacher perceptions of a school's tendency to be innovative was associated with a greater number of lessons taught and self-reported quality of delivery, and teacher-teacher affiliation was associated with a higher use of supplementary activities. The findings suggest that perceptions of a school's organizational climate impact teachers' implementation of SECD programs and have implications for school administrators and technical assistance providers as they work to implement and sustain prevention programs in schools.

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

OpenAIRE

Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

1996-01-01

BACKGROUND: Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. AIM: To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as with...

Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss.

Science.gov (United States)

Mankee, Anil; Petri, Michelle; Magder, Laurence S

2015-01-01

Multiple factors, including proteinuria, antiphospholipid syndrome, thrombocytopenia and hypertension, are predictive of pregnancy loss in systemic lupus erythematosus (SLE). In the PROMISSE study of predictors of pregnancy loss, only a battery of lupus anticoagulant tests was predictive of a composite of adverse pregnancy outcomes. We examined the predictive value of one baseline lupus anticoagulant test (dilute Russell viper venom time) with pregnancy loss in women with SLE. From the Hopkins Lupus Cohort, there were 202 pregnancies from 175 different women after excluding twin pregnancies and pregnancies for which we did not have a first trimester assessment of lupus anticoagulant. We determined the percentage of women who had a pregnancy loss in groups defined by potential risk factors. The lupus anticoagulant was determined by dilute Russell viper venom time with appropriate mixing and confirmatory testing. Generalised estimating equations were used to calculate p values, accounting for repeated pregnancies in the same woman. The age at pregnancy was 40 (3%). 55% were Caucasian and 34% African-American. Among those with lupus anticoagulant during the first trimester, 6/16 (38%) experienced a pregnancy loss compared with only 16/186 (9%) of other pregnancies (p=0.003). In addition, those with low complement or higher disease activity had a higher rate of pregnancy loss than those without (p=0.049 and 0.005, respectively). In contrast, there was no association between elevated anticardiolipin in the first trimester and pregnancy loss. The strongest predictor of pregnancy loss in SLE in the first trimester is the lupus anticoagulant. In addition, moderate disease activity by the physician global assessment and low complement measured in the first trimester were predictive of pregnancy loss. These data suggest that treatment of the lupus anticoagulant could be considered, even in the absence of history of pregnancy loss.

The Italian START-Register on Anticoagulation with Focus on Atrial Fibrillation

Science.gov (United States)

2015-01-01

START-Register – Survey on anTicoagulated pAtients RegisTer – is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) START-Register data shows that two-third of patients who started chronic anticoagulant treatment had NVAF, one-third of them was > 80 years with high prevalence of renal failure. PMID:26001109

Platelet factor 4 impairs the anticoagulant activity of activated protein C.

LENUS (Irish Health Repository)

Preston, Roger J S

2012-02-01

Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

Platelet factor 4 impairs the anticoagulant activity of activated protein C.

LENUS (Irish Health Repository)

Preston, Roger J S

2009-02-27

Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

Generic switching of warfarin and risk of excessive anticoagulation

DEFF Research Database (Denmark)

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

2016-01-01

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...

Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants

Directory of Open Access Journals (Sweden)

Luger S

2015-11-01

Full Text Available Sebastian Luger,1 Carina Hohmann,2 Daniela Niemann,1 Peter Kraft,3 Ignaz Gunreben,3 Tobias Neumann-Haefelin,2 Christoph Kleinschnitz,3 Helmuth Steinmetz,1 Christian Foerch,1 Waltraud Pfeilschifter1 1Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, 2Department of Neurology, Klinikum Fulda gAG, Fulda, 3Department of Neurology, University Hospital Würzburg, Würzburg, Germany Background: Oral anticoagulant therapy (OAT potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods: All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients’ adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results: In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3% (n=209. A total of 92% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9%; NOAC, 74.8%; P=0.243 with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion: One-year adherence to OAT after stroke is strong (>90% and patients

Comparing new anticoagulants.

Science.gov (United States)

Wooten, James M

2012-12-01

For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio)

Science.gov (United States)

Rattner, Barnett A.; Horak, Katherine E.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Meteyer, Carol U.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Johnston, John J.

2012-01-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/ or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Malavefes: A computational voice-enabled malaria fuzzy informatics software for correct dosage prescription of anti-malarial drugs

Directory of Open Access Journals (Sweden)

Olugbenga O. Oluwagbemi

2018-04-01

Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription

Microbial quality of some herbal solid dosage forms

African Journals Online (AJOL)

STORAGESEVER

2010-03-15

Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

Atrial fibrillation and stroke prevention practices in patients with candidacy for anticoagulation therapy

International Nuclear Information System (INIS)

Ullah, I.; Ahmad, S.; Hayat, Y.

2015-01-01

Background: Stroke secondary to Atrial Fibrillation is usually due to thrombi formed in the left atrium and left atrial appendage embolizing to cause ischemic stroke. Therefore, in patients with Atrial Fibrillation, antithrombotic therapy is recommended to prevent stroke. Vitamin K antagonist therapy is most widely used antithrombotic therapy for patients with valvular and non valvular AF. Aspirin is recommended only in low risk patients. This study was conducted to determine the stroke prevention practices in local patients with atrial fibrillation who were candidates for anticoagulation therapy. Method: This was descriptive cross sectional study conducted at Cardiovascular Department Lady Reading Hospital Peshawar and Cardiology Department Hayatabad Medical Complex Peshawar. Sampling technique was non probability consecutive. Patients visiting OPD of respective hospitals with EKG evidence of AF and having CHADES VASC score 2 or more or having mitral stenosis and AF were included in the study. Patients with additional indications for anticoagulation were excluded from the study. Results: A total of 205 patients with atrial fibrillation were studied. Mean age was 60.7±14.7 years. Male were 55.6 percentage (n=114) while 44.4 percentage (n=91) were female. Of these 149 (72.7 percentage) were candidates for anticoagulation based on CHA2DS2 VASc score of 2 and more or mitral stenosis with AF. Only 27.5 percentage (n=41) patients were adequately treated with anticoagulant therapy using VKA or novel oral anticoagulant drugs. Majority of them were getting dual antiplatelet therapy (DAPT). Conclusion: Most patients with AF and high risk characteristics for thromboembolism are not receiving proper stroke prevention therapies. (author)

Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

Directory of Open Access Journals (Sweden)

Pauline E Jullien

2010-03-01

Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

Does small mammal prey guild affect the exposure of predators to anticoagulant rodenticides?

International Nuclear Information System (INIS)

Tosh, D.G.; McDonald, R.A.; Bearhop, S.; Lllewellyn, N.R.; Fee, S.; Sharp, E.A.; Barnett, E.A.; Shore, R.F.

2011-01-01

Ireland has a restricted small mammal prey guild but still includes species most likely to consume anticoagulant rodenticide (AR) baits. This may enhance secondary exposure of predators to ARs. We compared liver AR residues in foxes (Vulpes vulpes) in Northern Ireland (NI) with those in foxes from Great Britain which has a more diverse prey guild but similar agricultural use of ARs. Liver ARs were detected in 84% of NI foxes, more than in a comparable sample of foxes from Scotland and similar to that of suspected AR poisoned animals from England and Wales. High exposure in NI foxes is probably due to greater predation of commensal rodents and non-target species most likely to take AR baits, and may also partly reflect greater exposure to highly persistent brodifacoum and flocoumafen. High exposure is likely to enhance risk and Ireland may be a sentinel for potential effects on predator populations. - Highlights: → Exposure of a predator to anticoagulant rodenticides was compared in Britain and Ireland. → Exposure was higher in Ireland. → Differences driven by small mammal prey guilds. → Ireland a potential sentinel for predator exposure to anticoagulants. - Restriction of the small mammal prey guild is associated with enhanced exposure of predators to anticoagulant rodenticides.

Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

Science.gov (United States)

Miller, Michael P; Trujillo, Toby C; Nordenholz, Kristen E

2014-04-01

The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Gaps in monitoring during oral anticoagulation: insights into care transitions, monitoring barriers, and medication nonadherence.

Science.gov (United States)

Rose, Adam J; Miller, Donald R; Ozonoff, Al; Berlowitz, Dan R; Ash, Arlene S; Zhao, Shibei; Reisman, Joel I; Hylek, Elaine M

2013-03-01

Among patients receiving oral anticoagulation, a gap of > 56 days between international normalized ratio tests suggests loss to follow-up that could lead to poor anticoagulation control and serious adverse events. We studied long-term oral anticoagulation care for 56,490 patients aged 65 years and older at 100 sites of care in the Veterans Health Administration. We used the rate of gaps in monitoring per patient-year to predict percentage time in therapeutic range (TTR) at the 100 sites. Many patients (45%) had at least one gap in monitoring during an average of 1.6 years of observation; 5% had two or more gaps per year. The median gap duration was 74 days (interquartile range, 62-107). The average TTR for patients with two or more gaps per year was 10 percentage points lower than for patients without gaps (P < .001). Patient-level predictors of gaps included nonwhite race, area poverty, greater distance from care, dementia, and major depression. Site-level gaps per patient-year varied from 0.19 to 1.78; each one-unit increase was associated with a 9.2 percentage point decrease in site-level TTR (P < .001). Site-level gap rates varied widely within an integrated care system. Sites with more gaps per patient-year had worse anticoagulation control. Strategies to address and reduce gaps in monitoring may improve anticoagulation control.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

Science.gov (United States)

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS₂ [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS₂ and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse.

Dermatotoxicity of epicutaneously applied anticoagulant warfarin

International Nuclear Information System (INIS)

Kataranovski, Milena; Prokic, Vera; Kataranovski, Dragan; Zolotarevski, Lidija; Majstorovic, Ivana

2005-01-01

Dermatotoxic effects of epicutaneous application of a first-generation anticoagulant, warfarin (WF) were examined in rats. Selected parameters of skin activity were determined 24 h following warfarin application, including metabolic viability of skin explants, some aspects of oxidative activity in skin tissue homogenates and inflammatory/immune relevant activity of epidermal cells from warfarin-treated skin. No changes in skin metabolic viability (MTT reduction) were noted ex vivo following WF application, suggesting the absence of immediate toxicity for skin. In contrast, increased formation of malondialdehyde (MDA), with a decrease in protein and non-protein thiols in homogenates of warfarin-treated skin was demonstrated, pointing to prooxidant activity in warfarin-treated skin. Increased costimulatory activity of epidermal cells isolated from warfarin-exposed skin in Con-A-stimulated T-cell activation/proliferation assay was noted, reflecting proinflammatory and immune-modulating capacity of warfarin for epidermis. No evident differences in skin histology between control and warfarin-treated skin were found at that time point, while striking changes in tissue integrity, cellularity and appearance 72 h following WF application were noted. The observed histological picture probably reflects a regenerative/inflammatory program related to oxidant/inflammation-type warfarin-evoked injury to the skin. Presented data demonstrate the potential of epicutaneously applied warfarin to modulate local skin activity in rats

Poor anticoagulation control in patients taking warfarin at a tertiary and districtlevel prothrombin clinic in Cape Town South Africa

Directory of Open Access Journals (Sweden)

I Ebrahim

2018-05-01

urgent need to improve anticoagulation control of patients receiving warfarin in SA. Validated dosing algorithms are required, and access to lower warfarin dosage formulations may optimise individual dose titration. Advocacy for these formulations is advised. 

School-based early childhood education and age-28 well-being: effects by timing, dosage, and subgroups.

Science.gov (United States)

Reynolds, Arthur J; Temple, Judy A; Ou, Suh-Ruu; Arteaga, Irma A; White, Barry A B

2011-07-15

Advances in understanding the effects of early education have benefited public policy and developmental science. Although preschool has demonstrated positive effects on life-course outcomes, limitations in knowledge on program scale, subgroup differences, and dosage levels have hindered understanding. We report the effects of the Child-Parent Center Education Program on indicators of well-being up to 25 years later for more than 1400 participants. This established, publicly funded intervention begins in preschool and provides up to 6 years of service in inner-city Chicago schools. Relative to the comparison group receiving the usual services, program participation was independently linked to higher educational attainment, income, socioeconomic status (SES), and health insurance coverage, as well as lower rates of justice-system involvement and substance abuse. Evidence of enduring effects was strongest for preschool, especially for males and children of high school dropouts. The positive influence of four or more years of service was limited primarily to education and SES. Dosage within program components was mostly unrelated to outcomes. Findings demonstrate support for the enduring effects of sustained school-based early education to the end of the third decade of life.

Scoring and psychometric validation of the Perception of Anticoagulant Treatment Questionnaire (PACT-Q©

Directory of Open Access Journals (Sweden)

Essers B

2009-04-01

Full Text Available Abstract Background The 'Perception of Anti-Coagulant Treatment Questionnaire' (PACT-Q was developed to assess patients' expectations of, and satisfaction with their anticoagulant treatment. This questionnaire needs to be finalised and psychometrically validated. Methods The PACT-Q was included in the United States, the Netherlands and France into three phase III multinational clinical trials conducted to evaluate efficacy and safety of a new long-acting anticoagulant drug (idraparinux compared to vitamin K antagonist (VKA. PACT-Q was administered to patients with deep venous thrombosis (DVT, atrial fibrillation (AF or pulmonary embolism (PE at Day 1, to assess patients' expectations, and at 3 and 6 months to assess patients' satisfaction and treatment convenience and burden. The final structure of the PACT-Q (Principal Component Analysis – PCA – with Varimax Rotation was first determined and its psychometric properties were then measured with validity of the structure (Multitrait analysis, internal consistency reliability (Cronbach's alpha coefficients and known-group validity. Results PCA and multitrait analyses showed the multidimensionality of the "Treatment Expectations" dimension, comprising 7 items that had to be scored independently. The "Convenience" and "Burden of Disease and Treatment" dimensions of the hypothesised original structure of the questionnaire were combined, thus resulting in 13 items grouped into the single dimension "Convenience". The "Anticoagulant Treatment Satisfaction" dimension remained unchanged and included 7 items. All items of the "Convenience" and "Anticoagulant Treatment Satisfaction" dimensions displayed good convergent and discriminant validity. The internal consistency reliability was good, with a Cronbach's alpha of 0.84 for the "Convenience" dimension, and 0.76 for the "Anticoagulant Treatment Satisfaction" dimension. Known-group validity was good, especially with regard to occurrence of

Characterization and structural analysis of a potent anticoagulant phospholipase A2 from Pseudechis australis snake venom.

Science.gov (United States)

Du, Qianyun Sharon; Trabi, Manuela; Richards, Renée Stirling; Mirtschin, Peter; Madaras, Frank; Nouwens, Amanda; Zhao, Kong-Nan; de Jersey, John; Lavin, Martin F; Guddat, Luke W; Masci, Paul P

2016-03-01

Pseudechis australis is one of the most venomous and lethal snakes in Australia. Numerous phospholipase A2 (PLA2) isoforms constitute a major portion of its venom, some of which have previously been shown to exhibit not only enzymatic, but also haemolytic, neurotoxic and anticoagulant activities. Here, we have purified a potent anticoagulant PLA2 (identified as PA11) from P. australis venom to investigate its phospholipase, anticoagulant, haemolytic and cytotoxic activities and shown that addition of 11 nM PA11 resulted in a doubling of the clotting time of recalcified whole blood. We have also demonstrated that PA11 has high PLA2 enzymatic activity (10.9 × 10(4) Units/mg), but low haemolytic activity (0.6% of red blood cells hydrolysed in the presence of 1 nM PA11). PA11 at a concentration lower than 600 nM is not cytotoxic towards human cultured cells. Chemical modification experiments using p-bromophenacyl bromide have provided evidence that the catalytic histidine of PA11 is critical for the anticoagulant activity of this PLA2. PA11 that was subjected to trypsin digestion without previous reduction and alkylation of the disulfide bonds maintained enzymatic and anticoagulant activity, suggesting that proteolysis alone cannot abolish these properties. Consistent with these results, administration of PA11 by gavage in a rabbit stasis thrombosis model increased the clotting time of recalcified citrated whole blood by a factor of four. These data suggest that PA11 has potential to be developed as an anticoagulant in a clinical setting. Copyright © 2015. Published by Elsevier Ltd.

21 CFR 520.905 - Fenbendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy.

Science.gov (United States)

Labovitz, Daniel L; Shafner, Laura; Reyes Gil, Morayma; Virmani, Deepti; Hanina, Adam

2017-05-01

This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. © 2017 American Heart Association, Inc.

Buccal Dosage Forms: General Considerations for Pediatric Patients.

Science.gov (United States)

Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

2017-02-01

The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

Safety and efficacy of anticoagulation for secondary stroke prevention in atrial fibrillation patients: The AMADEUS trial

NARCIS (Netherlands)

Lane, D.A.; Kamphuisen, P.W.; Minini, P.; Buller, H.R.; Lip, G.Y.H.

2010-01-01

ackground: Patients with atrial fibrillation (AF) and previous ischemic stroke are at high risk of recurrent stroke, but are also perceived to be at increased bleeding risk while treated with anticoagulants. Methods: Post-hoc analyses examined the efficacy and safety of anticoagulation of 4576 AF

Major cerebral events in Staphylococcus aureus infective endocarditis: is anticoagulant therapy safe?

DEFF Research Database (Denmark)

Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars

2009-01-01

OBJECTIVES: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). METHODS: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset...... of admission and during hospitalization. RESULTS: Overall, 70 out of 175 patients (40%; 95% CI: 33-47%) experienced major cerebral events during the course of the disease, cerebral ischaemic stroke occured in 59 patients (34%; 95% CI: 27-41%), cerebral infection in 23 patients (14%; 95% CI: 9...

The first pharmacist-managed anticoagulation clinic under a collaborative practice agreement in Qatar: clinical and patient-oriented outcomes.

Science.gov (United States)

Elewa, H F; AbdelSamad, O; Elmubark, A E; Al-Taweel, H M; Mohamed, A; Kheir, N; Mohamed Ibrahim, M I; Awaisu, A

2016-08-01

Optimal outpatient anticoagulation management requires a systematic and coordinated approach. Extensive evidence regarding the benefits of pharmacist-managed anticoagulation services has been reported in the literature. The quality and outcomes associated with pharmacist-managed anticoagulation clinics under collaborative practice agreements in the Middle East have rarely been reported. The first pharmacist-managed ambulatory anticoagulation clinic in Qatar was launched at Al-Wakrah Hospital in March 2013. The objectives of this study were to: (i) describe the practice model of the clinic, (ii) evaluate the quality of the clinic [i.e. the time in therapeutic range (TTR)] and the clinical outcomes (i.e. the efficacy and safety), and (iii) determine the patients' satisfaction and overall quality of life (QoL). Clinical outcome data were collected through a retrospective chart review of all patients managed from March 2013 to October 2014 at the pharmacist-managed anticoagulation clinic. Furthermore, the patient-oriented outcomes data were prospectively collected using the 24-item Duke Anticoagulation Satisfaction Scale (DASS). Each item was assessed using a 7-point Likert-type scale on which lower scores indicated better QoL and greater satisfaction. The clinical outcome data analyses included 119 patients who were enrolled at the clinic during the 19-month study period. The mean number of international normalized ratio (INR) tests/month was 65 ± 9, the average testing frequency was 2·7 ± 1·6 weeks, and the average %TTR was 76·8 ± 22·9%. There was one major bleeding event (0·67%/year), 12 minor bleeding events (8%/year) and two thromboembolic events (1·35%/year) recorded during the study period. Of the 119 patients, 50 participated in the satisfaction and QoL survey. The median (IQR) total QoL score of these subjects was 63 (48) (minimum-maximum achievable score: 24-168). Seventy-six per cent of the patients indicated 'a lot to very much' in terms of their

The risk of venous thromboembolism with aspirin compared to anticoagulants after hip and knee arthroplasty.

Science.gov (United States)

Chu, Janet N; Maselli, Judith; Auerbach, Andrew D; Fang, Margaret C

2017-07-01

Recent guidelines include aspirin as an option to prevent venous thromboembolism (VTE) in selected patients undergoing hip or knee replacement surgery. However, the efficacy of aspirin after arthroplasty has not been well-defined, particularly in more contemporary patient populations. We compared rates of post-operative VTE between patients who received aspirin-only versus anticoagulants after hip or knee arthroplasty, using data from a large US-based administrative database. We conducted a retrospective cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621 who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery. We compared the risk of post-operative VTE between patients receiving aspirin-only vs. anticoagulants, controlling for clinical and hospital characteristics using multivariable logistic regression with propensity score adjustment. Aspirin-only prophylaxis was administered to 7.5% of patients after knee arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in 2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip arthroplasty. Compared to anticoagulants, aspirin was not associated with a higher risk for post-operative VTE either after knee arthroplasty (adjusted odds ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR 0.82 [0.45-1.51]). Aspirin was uncommonly administered as the sole prophylactic agent after hip or knee arthroplasty in this study. However, patients who received aspirin-only had similar rates of post-operative VTE compared to patients who received anticoagulants. Further research should focus on distinguishing which patients benefit more from anticoagulants versus aspirin after arthroplasty. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intercavitary implants dosage calculation

International Nuclear Information System (INIS)

Rehder, B.P.

The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

Fatal rebleeding following coil embolization of cerebral aneurysms: the role of long-term systemic anticoagulation

International Nuclear Information System (INIS)

Sinson, G.; Bagley, L.J.; Hurst, R.W.; Flamm, E.S.

2001-01-01

Embolization of cerebral aneurysms has become a common technique. Its impact on subsequent medical management of the patient is not well known. We report two patients who presented in a poor neurological grade after subarachnoid hemorrhage from posterior communicating artery aneurysms. Both were treated by coil embolization and both developed subclavian vein thrombosis, requiring systemic anticoagulation, initiated 11 and 21 days after embolization, respectively. Both developed a large, fatal intracranial hemorrhage adjacent to the embolized aneurysm in the fourth week of anticoagulation. Systemic anticoagulation of patients who have had a ruptured aneurysm treated by coil embolization may carry a significant risk of rebleeding. Alternate management strategies should be considered in these patients. (orig.)

Fatal rebleeding following coil embolization of cerebral aneurysms: the role of long-term systemic anticoagulation

Energy Technology Data Exchange (ETDEWEB)

Sinson, G. [Dept. of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Bagley, L.J.; Hurst, R.W. [Dept. of Radiology-Neuroradiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Flamm, E.S. [Hyman-Newman Institute for Neurology and Neurosurgery, New York, NY (United States)

2001-05-01

Embolization of cerebral aneurysms has become a common technique. Its impact on subsequent medical management of the patient is not well known. We report two patients who presented in a poor neurological grade after subarachnoid hemorrhage from posterior communicating artery aneurysms. Both were treated by coil embolization and both developed subclavian vein thrombosis, requiring systemic anticoagulation, initiated 11 and 21 days after embolization, respectively. Both developed a large, fatal intracranial hemorrhage adjacent to the embolized aneurysm in the fourth week of anticoagulation. Systemic anticoagulation of patients who have had a ruptured aneurysm treated by coil embolization may carry a significant risk of rebleeding. Alternate management strategies should be considered in these patients. (orig.)

Intermittent vs. Continuous Anticoagulation theRapy in patiEnts with Atrial Fibrillation (iCARE-AF): a randomized pilot study.

Science.gov (United States)

Stavrakis, Stavros; Stoner, Julie A; Kardokus, Joel; Garabelli, Paul J; Po, Sunny S; Lazzara, Ralph

2017-01-01

We hypothesized that intermittent anticoagulation based on daily rhythm monitoring using the novel oral anticoagulants (NOACs) is feasible and safe among patients with paroxysmal atrial fibrillation (AF). Patients with paroxysmal AF and ≥1 risk factors for stroke were randomized to either intermittent or continuous anticoagulation. Those in the intermittent group were instructed to transmit a daily ECG using an iPhone-based rhythm monitoring device. If AF was detected, patients received one of the NOACs for 48 h-1 week. Patients who failed to transmit an ECG for three consecutive days or more than 7 days total were crossed over to continuous anticoagulation. Patients in the continuous group received one of the NOACs. Fifty-eight patients were randomized to either intermittent (n = 29) or continuous anticoagulation (n = 29). Over a median follow-up of 20 months, 20 patients in the intermittent group failed to submit a daily ECG at least once (median three failed submissions). Four patients (14 %) crossed over to continuous anticoagulation due to failure to submit an ECG for three consecutive days. One stroke (continuous group) occurred during the study. Major bleeding occurred in two patients in the continuous and one patient in the intermittent group, after crossing over to continuous anticoagulation. In a prespecified per-protocol analysis, gastrointestinal bleeding was more frequent in the continuous group (16 vs. 0 %; p = 0.047). Intermittent anticoagulation based on daily rhythm monitoring is feasible and may decrease bleeding in low-risk patients with paroxysmal AF. A larger trial, adequately powered to detect clinical outcomes, is warranted.

[Clinical scores for the risk of bleeding with or without anticoagulation].

Science.gov (United States)

Junod, Alain

2016-09-14

The assessment of hemorragic risk related to therapeutic anticoagulation is made difficult because of the variety of existing drugs, the heterogeneity of treatment strategies and their duration. Six prognostic scores have been analyzed. For three of them, external validations have revealed a marked decrease in the discrimination power. One British study, Qbleed, based on the data of more than 1 million of ambulatory patients, has repeatedly satisfied quality criteria. Two scores have also studied the bleeding risk during hospital admission for acute medical disease. The development of new and effective anticoagulants with fewer side-effects is more likely to solve this problem than the production of new clinical scores.

Bleeding complications during anticoagulant treatment in patients with cancer

NARCIS (Netherlands)

Kamphuisen, Pieter W.; Beyer-Westendorf, Jan

Patients with cancer have an increased risk of bleeding complications, of which some are fatal. This risk is influenced by chemotherapy, cancer type and stage, thrombocytopenia, renal function, and previous bleeding. Since many cancer patients receive anticoagulant treatment for prophylaxis or

Self-management of oral anticoagulant therapy in two centers

DEFF Research Database (Denmark)

Nilsson, Hanna; Grove, E; Larsen, Torben Bjerregaard

of Cardiology, Aarhus University Hospital, Aarhus; 3Department of Cardiology, Aalborg Hospital & Department of Health Science and Technology, Aalborg University, Aalborg, Denmark haana_86@hotmail.com Objectives: Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists have...

Comprehensive review on additives of topical dosage forms for drug delivery.

Science.gov (United States)

Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-12-01

Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

Radiation dosage of various CT-methods in lung diagnostics

International Nuclear Information System (INIS)

Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

1996-01-01

Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

Hydraulic Modular Dosaging Systems for Machine Drives

Directory of Open Access Journals (Sweden)

A. J. Kotlobai

2005-01-01

Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

Science.gov (United States)

Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

2018-02-01

Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quality of Vitamin K Antagonist Anticoagulation in Spain: Prevalence of Poor Control and Associated Factors.

Science.gov (United States)

Anguita Sánchez, Manuel; Bertomeu Martínez, Vicente; Cequier Fillat, Ángel

2015-09-01

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011). There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Vitamin K and stability of oral anticoagulant therapy

NARCIS (Netherlands)

Rombouts, Eva Karolien

2011-01-01

One of the causes of unstable anticoagulation is a variable vitamin K intake. The main objective of this thesis was to test the hypothesis that the INR is particularly sensitive to changes in vitamin K intake when vitamin K status is low, and that patients with a low vitamin K intake would therefore

Non-vitamin K antagonist oral anticoagulants (NOAC) in the treatment of venous thromboembolism

OpenAIRE

Sebastian Werth; Jan Beyer-Westendorf

2015-01-01

In case of venous thromboembolism (VTE) e ective anticoagulation is needed. The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) for VTE therapy o ers new treatment options and, in general, simpli es VTE therapy compared to the concept of LMWH/ VKA. At the same time, NOACs may help to improve the clinical outcome of patients with VTE as trial results consistently indicated the reduction in major bleeding complications. There are several reasons to use NOAC in special p...

Diagnostic imaging of severe rectus sheath hematoma complicating anticoagulant therapy

International Nuclear Information System (INIS)

Blum, A.; Bui, P.; Boccaccini, H.; Bresler, L.; Claudon, M.; Boissel, P.; Regent, D.

1995-01-01

CT were performed in thirteen patients (12 women, 1 man) aged from 53 to 90 (mean age, 74) with severe RSH. Five patients also underwent ultrasound examination and three MR examination. Nine patients (69%) were receiving subcutaneous injection of heparin, three (23%) oral anticoagulant therapy and one continuous IV infusion of heparin. Clinical diagnosis was reached in 6 cases. Excessive activity of anticoagulant therapy was noted in 4 cases. The location of the RSH, their densities and their signals were analysed. All the RSH were mostly developed in the lower third of the abdominal wall, had a large spreading into the Retzius space and compressed the bladder and/or the bowels. RSH were all hyperdense and in 8 cases (61%) a fluid-fluid level due to the hematocrit effect was noted. In one case, a retroperitoneal hematoma was discovered. The extension of the RSH was well delineated with MRI. The RSH showed itself with heterogeneous signal intensities with areas of high-signal-intensity on T1-weighted images. Fluid-fluid levels and a concentric ring sign were also noted. Older women with subcutaneous injection of heparin are especially prone to RSH even though there is no overall excessive activity of anticoagulant therapy. Clinical and biological diagnosis may be difficult. CT scan is the exam of choice to reach a precise and acute diagnosis of RSH. (authors). 34 refs., 8 figs

Renal Infarction during Anticoagulant Therapy after Living Donor Liver Transplantation

Directory of Open Access Journals (Sweden)

Shinji Onda

2018-04-01

Full Text Available Introduction: Liver transplant recipients are at risk for complications of vascular thrombosis. The reconstructed hepatic artery and portal vein thrombosis potentially result in hepatic failure and graft loss. Renal infarction is a rare clinical condition, but in severe cases, it may lead to renal failure. We herein report a case of renal infarction after living donor liver transplantation (LDLT during anticoagulant therapy. Case Presentation: A 60-year-old woman with end-stage liver disease due to primary biliary cholangitis underwent LDLT with splenectomy. Postoperatively, tacrolimus, mycophenolate mofetil, and steroid were used for initial immunosuppression therapy. On postoperative day (POD 5, enhanced computed tomography (CT revealed splenic vein thrombosis, and anticoagulant therapy with heparin followed by warfarin was given. Follow-up enhanced CT on POD 20 incidentally demonstrated right renal infarction. The patient’s renal function was unchanged and the arterial flow was good, and the splenic vein thrombosis resolved. At 4 months postoperatively, warfarin was discontinued, but she developed recurrent splenic vein thrombosis 11 months later, and warfarin was resumed. As of 40 months after transplantation, she discontinued warfarin and remains well without recurrence of splenic vein thrombosis or renal infarction. Conclusion: Renal infarction is a rare complication of LDLT. In this case, renal infarction was incidentally diagnosed during anticoagulant therapy and was successfully treated.

Emergency management of major bleeding in a case of maxillofacial trauma and anticoagulation: utility of prothrombin complex concentrates in the shock room

Directory of Open Access Journals (Sweden)

Alessandro Morotti

2015-03-01

Full Text Available Life-threatening bleeding in anticoagulation with Warfarin is an emergency challenging issue. Several approaches are available to treat bleeding in either over-anticoagulation or propeanticoagulation, including vitamin K, fresh frozen plasma and prothrombin complex concentrates (PCC administration. In coexisting trauma-induced bleeding and anticoagulation, reversal of anticoagulation must be a rapid and highly effective procedure. Furthermore the appropriate treatment must be directly available in each shock rooms to guarantee the rapid management of the emergency. PCC require a simple storage, rapid accessibility, fast administration procedures and high effectiveness. Here we report the utility of PCC in management of a craniofacial trauma in proper-anticoagulation.

Safety of percutaneous nephrolithotomy in patients on chronic anticoagulant or antiplatelet therapy.

Science.gov (United States)

Fernández-Baltar, C; Pérez-Fentes, D; Sánchez-García, J F; García-Freire, C

2018-01-22

In developed countries, the incidence of cardiovascular disease is increasing, therefore, anticoagulant and antiplatelet drugs are a widespread treatment nowadays. Percutaneous nephrolithotomy (PNL) is the first-line treatment for large or complex stones (> 2 cm) and remains an alternative for the smaller ones. The objective of this study is to analyze whether PNL surgery is a safe procedure in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. We retrospectively studied 301 patients who underwent PNL in our hospital between 2008 and 2016 and identified 46 patients on chronic antiplatelet or anticoagulation treatment. With respect to PNL outcomes, the stone-free rate was similar (78 vs 74%, p = 0.762) in both groups, without any significant differences in the overall postoperative complications (17 vs 26%, p = 0.203). The incidence of hemorrhagic complications was similar between groups (12 vs 9%, p = 0.492), as demonstrated by the mean drop in hemoglobin (Hb), which was comparable in both cohorts (2.2 ± 1.3 vs 2.0 ± 1.4 p = 0.270) and the blood transfusion rate (14% in group A and 8% in group B, p = 0.205). No thromboembolic events were found within the year after the PNL procedure. PNL is a safe and effective intervention in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. Although our study demonstrates the feasibility of this protocol, new scientific evidence aims to stratify the thromboembolic and bleeding risk of each patient to individualize the perioperative management thereafter.

Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

Science.gov (United States)

Maddula, Surekha; Ansell, Jack

2013-08-01

The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant and antiproliferative properties through straightforward chemical modifications.

Science.gov (United States)

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2018-02-01

The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'-GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions, previously investigated. The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones. Copyright © 2017 Elsevier Inc. All rights reserved.

Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial.

Science.gov (United States)

Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A

2007-02-01

Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin. In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070). The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75). Oral

Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation

DEFF Research Database (Denmark)

Fosbøl, Emil L; Vinding, Naja Emborg; Lamberts, Morten

2017-01-01

Aims: After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran...

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

Science.gov (United States)

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

2017-07-01

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

Standardisation of the Laboratory Control of Anticoagulant Therapy

African Journals Online (AJOL)

1974-09-11

Sep 11, 1974 ... Anticoagulant therapy with the coumarin group of drugs has been used in clinical practice for more than a quarter of a century. The most widely used form of laboratory control of the treatment is the Quick one-stage prothrom·- bin time. I. This simple test proved to be satisfactory in most cases, but discrepant ...

Factors Affecting Outcome in Treatment of Chronic Subdural Hematoma in ICU Patients: Impact of Anticoagulation.

Science.gov (United States)

Szczygielski, Jacek; Gund, Sina-Maria; Schwerdtfeger, Karsten; Steudel, Wolf-Ingo; Oertel, Joachim

2016-08-01

The use of anticoagulants and older age are the main risk factors for chronic subdural hematoma (CSDH). Because the age of the population and use of anticoagulants are increasing, a growing number of CSDH cases is expected. To address this issue, we analyzed the impact of anticoagulants on postsurgical outcome in patients in the intensive care unit (ICU). Demographic data, coagulation parameters, surgical details, radiologic appearance of hematoma, Glasgow Coma Scale (GCS) score on admission, and Glasgow Outcome Scale (GOS) score on discharge were retrieved and retrospectively analyzed in 98 patients with CSDH treated in the neurosurgical ICU using correlation coefficient tests and multivariate analysis test. Overall outcome was good (GOS score 4 and 5) in 55.1% of patients. Overall mortality was 9.1%. There was a correlation between GCS score on admission and GOS score. There was no correlation between hematoma thickness/radiologic appearance and impaired coagulation. Disturbance in thrombocyte function (usually resulting from aspirin intake) correlated with improved outcome, whereas warfarin-related coagulopathy correlated with poor recovery. Nevertheless, patients with thrombocytopathy presented with better initial GCS scores. Neither hematoma size nor recurrence rate affected the outcome. The size of CSDH was not associated with poor outcome and is not necessarily determined by the use of anticoagulants. Coagulopathy does not rule out a good outcome, but the impact of anticoagulation on treatment results in CSDH varies between the main groups of drugs (warfarin vs. antiplatelet drugs). Patients in good neurologic condition on ICU admission have better chances of recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Language, literacy, and communication regarding medication in an anticoagulation clinic: a comparison of verbal vs. visual assessment.

Science.gov (United States)

Schillinger, Dean; Machtinger, Edward L; Wang, Frances; Palacios, Jorge; Rodriguez, Maytrella; Bindman, Andrew

2006-01-01

Despite the importance of clinician-patient communication, little is known about rates and predictors of medication miscommunication. Measuring rates of miscommunication, as well as differences between verbal and visual modes of assessment, can inform efforts to more effectively communicate about medications. We studied 220 diverse patients in an anticoagulation clinic to assess concordance between patient and clinician reports of warfarin regimens. Bilingual research assistants asked patients to (1) verbalize their prescribed weekly warfarin regimen and (2) identify this regimen from a digitized color menu of warfarin pills. We obtained clinician reports of patient regimens from chart review. Patients were categorized as having regimen concordance if there were no patient-clinician discrepancies in total weekly dosage. We then examined whether verbal and visual concordance rates varied with patient's language and health literacy. Fifty percent of patients achieved verbal concordance and 66% achieved visual concordance with clinicians regarding the weekly warfarin regimen (P visual discordance. Shifting from verbal to visual modes was associated with greater patient-provider concordance across all patient subgroups, but especially for those with communication barriers.Clinician-patient discordance regarding patients' warfarin regimen was common but occurred less frequently when patients used a visual aid. Visual aids may improve the accuracy of medication assessment, especially for patients with communication barriers.

Pulsed electric field extraction enhanced anti-coagulant effect of fungal polysaccharide from Jew's ear (Auricularia auricula).

Science.gov (United States)

Li, Changtian; Mao, Xinxin; Xu, Baojun

2013-01-01

As a Chinese herbal medicine, Jew's ear has been known for its anti-coagulant effects. Hence it is worthwhile developing an effective technique to extract active components. To find the optimal extraction condition and to identify the best strain to yield fungal polysaccharide with anti-coagulant activity. Three strains of Jew's ear from Jilin Province, named as 988, DY 18 and FS 02, and three extraction techniques, namely, high intensity pulsed electric fields (HIPEF), microwave-assisted extraction method (MAEM) and ultrasonic-assisted extraction method (UAEM), were applied to optimise the extraction conditions. The crude extracts and polysaccharides were further determined for anti-coagulant activities. All extracts prolonged blood clotting time as compared to reagent control. The HIPEF exhibited the most remarkable effect among the three extraction techniques. The anti-coagulant activities of extracts were enhanced with increasing electric field strength when the field strength reached 24 kV/cm. Current results suggest that the HIPEF technique will be an effective method in the manufacture of bioactive natural polysaccharide. Copyright © 2012 John Wiley & Sons, Ltd.

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

Science.gov (United States)

Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R

2016-01-01

Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the

The Anticoagulation of Calf Thrombosis (ACT project: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Horner Daniel

2012-04-01

Full Text Available Abstract Background Half of all lower limb deep vein thrombi (DVT in symptomatic ambulatory patients are located in the distal (calf veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis. Methods ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1 a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2 the incidence of major and minor bleeding episodes; (3 the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4 the incidence of venous thromboembolism (VTE recurrence at 2 years. Discussion The ACT trial

21 CFR 520.1696 - Penicillin oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

Science.gov (United States)

Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

2014-10-01

The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

Science.gov (United States)

Lee, Taewoo; Biddle, Andrea K.; Lionaki, Sofia; Derebail, Vimal K.; Barbour, Sean J.; Tannous, Sameer; Hladunewich, Michelle A.; Hu, Yichun; Poulton, Caroline J.; Mahoney, Shannon L.; Jennette, J. Charles; Hogan, Susan L.; Falk, Ronald J.; Cattran, Daniel C.; Reich, Heather N.; Nachman, Patrick H.

2014-01-01

Primary membranous nephropathy is associated with increased risk of venous thromboembolic events, which are inversely correlated with serum albumin levels. To evaluate the potential benefit of prophylactic anticoagulation (venous thromboembolic events prevented) relative to the risk (major bleeds), we constructed a Markov decision model. The venous thromboembolic event risk according to serum albumin was obtained from an inception cohort of 898 patients with primary membranous nephropathy. Risk estimates of hemorrhage were obtained from a systematic literature review. Benefit-to-risk ratios were predicted according to bleeding risk and serum albumin. This ratio increased with worsening hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity analysis, to account for uncertainty in risk estimates, confirmed these trends. From these data, we constructed a tool to estimate the likelihood of benefit based on an individual’s bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio (http://www.gntools.com). This tool provides an approach to the decision of prophylactic anticoagulation personalized to the individual’s needs and adaptable to dynamic changes in health status and risk profile. PMID:24336031

Electroconvulsive therapy and anticoagulation after pulmonary embolism: a case report

Directory of Open Access Journals (Sweden)

Julio Cesar Lazaro

2014-07-01

Full Text Available Introduction Electroconvulsive therapy (ECT is considered the most effective treatment for catatonia regardless its underlying condition. The rigid fixed posture and immobility observed in catatonia may lead to several clinical complications, of which, pulmonary embolism (PE is one of the most severe. The rapid improvement of the psychiatric condition in catatonia-related PE is essential, since immobility favors the occurrence of new thromboembolic events and further complications. In that scenario, ECT should be considered, based on a risk-benefit analysis, aiming at the faster resolution of the catatonia. Methods Case report and literature review. Results A 66-years-old woman admitted to the psychiatric ward with catatonia due to a depressive episode presented bilateral PE. Clinically stable, but still severely depressed after a trial of antidepressants, she was treated with ECT in the course of full anticoagulation with enoxaparin. After five ECT sessions, her mood was significantly better and she was walking and eating spontaneously. She did not present complications related either to PE or to anticoagulation. After the eighth ECT session, she evolved with hypomania, which was managed with oral medication adjustments. The patient was completely euthymic at discharge. Conclusion The case we presented provides further evidence to the anecdotal case reports on the safety of ECT in the course of concomitant full anticoagulant therapy after PE, and illustrates how, with the proper precautions, the benefits of ECT in such condition might outweigh its risks.

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

Science.gov (United States)

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

Anticoagulant drugs increase natural killer cell activity in lung cancer

Czech Academy of Sciences Publication Activity Database

Bobek, M.; Boubelík, Michael; Fišerová, Anna; Luptovcová, Martina; Vannucci, Luca; Kacprzak, G.; Kolodzej, J.; Majewski, A.M.; Hoffman, R. M.

2005-01-01

Roč. 47, č. 2 (2005), s. 215-223 ISSN 0169-5002 Institutional research plan: CEZ:AV0Z5052915 Keywords : anticoagulant drugs * lung cancer * NK cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.172, year: 2005

Self-monitoring and self-management of oral anticoagulation.

Science.gov (United States)

Heneghan, Carl J; Garcia-Alamino, Josep M; Spencer, Elizabeth A; Ward, Alison M; Perera, Rafael; Bankhead, Clare; Alonso-Coello, Pablo; Fitzmaurice, David; Mahtani, Kamal R; Onakpoya, Igho J

2016-07-05

The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010. To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions . Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics and used GRADE methodology to assess the quality of evidence. We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0

Congenital Malformations Associated with the Administration of Oral Anticoagulants During Pregnancy

Science.gov (United States)

Pettifor, J. M.; Benson, R.

1975-01-01

Reported are case histories of three infants with congenital malformations (including defective formation of the nose and hands) associated with ingestion of oral anticoagulants during the first trimester of pregnancy. (CL)

beta. -Amyloid gene dosage in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

1988-01-11

The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

Utilization of Oral Anticoagulation in a Teaching Hospital in Nigeria

African Journals Online (AJOL)

optimal antithrombotic effect. The oral drugs ... vitamin K-dependent clotting factors, which include factors. II, VII, IX, and X, ... hyperthyroidism) and those that decrease INR (pharmacokinetic: Barbiturates ... of anticoagulation, drug dosing, treatment outcome and .... national guidelines, and performance on quality measures.

Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

Science.gov (United States)

Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

2005-09-01

Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin.

Science.gov (United States)

Pan, Chang-Jiang; Hou, Yan-Hua; Zhang, Bin-Bin; Zhang, Lin-Cai

2014-01-01

This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Current practice of antiplatelet and anticoagulation management in post-cardiac surgery patients: a national audit.

Science.gov (United States)

Hosmane, Sharath; Birla, Rashmi; Marchbank, Adrian

2012-04-01

The Audit and Guidelines Committee of the European Association for Cardio-Thoracic Surgery recently published a guideline on antiplatelet and anticoagulation management in cardiac surgery. We aimed to assess the awareness of the current guideline and adherence to it in the National Health Service through this National Audit. We designed a questionnaire consisting of nine questions covering various aspects of antiplatelet and anticoagulation management in post-cardiac surgery patients. A telephonic survey of the on-call cardiothoracic registrars in all the cardiothoracic centres across the UK was performed. All 37 National Health Service hospitals in the UK with 242 consultants providing adult cardiac surgical service were contacted. Twenty (54%) hospitals had a unit protocol for antiplatelet and anticoagulation management in post-cardiac surgery. Only 23 (62.2%) registrars were aware of current European Association for Cardio-Thoracic Surgery guidelines. Antiplatelet therapy is variable in the cardiac surgical units across the country. Low-dose aspirin is commonly used despite the recommendation of 150-300 mg. The loading dose of aspirin within 24 h as recommended by the guideline is followed only by 60.7% of surgeons. There was not much deviation from the guideline with respect to the anticoagulation therapy.

Purification, structural characterization and anticoagulant properties of fucosylated chondroitin sulfate isolated from Holothuria mexicana.

Science.gov (United States)

Mou, Jiaojiao; Wang, Cong; Li, Wenjing; Yang, Jie

2017-05-01

A novel fucosylated chondroitin sulfate (HmG) was isolated from sea cucumber Holothuria mexicana, the structure of which was characterized by monosaccharide composition, disaccharide composition, IR, 1 H and 13 C NMR spectrum, additionally with two dimensional NMR spectrum of degraded HmG (DHmG). The backbone of HmG was identified as chondroitin 6-O sulfate, while the major O-4 sulfated fucose branches linked to O-3 position of glucuronic acid in almost every disaccharide unit. The anticoagulant activities of HmG and DHmG were assessed and compared with heparin and low molecular weight heparin. The results indicated that HmG and DHmG both could significantly prolong the activated partial thrombo-plastin time, and the properties were well related to its molecular weight. DHmG showed similar anticoagulant properties to low molecular weight heparin with less bleeding risks, making it a safer anticoagulant drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.

Science.gov (United States)

Hofmann, Eveline; Faller, Nicolas; Limacher, Andreas; Méan, Marie; Tritschler, Tobias; Rodondi, Nicolas; Aujesky, Drahomir

2016-01-01

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.

Cost evaluation of two methods of post tooth extraction hemostasis in patients on anticoagulant therapy.

Science.gov (United States)

Zusman, S P; Lustig, J P; Bin Nun, G

1993-06-01

The classical management of patients on oral anticoagulant therapy included hospitalisation, cessation of the anticoagulant agent, and extraction of teeth when the prothrombine levels rise. This method was substituted in the High Risk Dental Clinic at Barzilai Medical Center in Ashkelon by use of a tissue sealant (Tisseel) which does not need hospitalisation nor cessation of the anticoagulant therapy. In comparing the last 23 sessions employing the former method to the first 23 sessions using the new method there were significant differences in the cost effectiveness for the health system, provider, insurer and patient. Despite the fact that from the health system point of view the new method is much more cost effective, there is no financial incentive for the provider (hospital) nor awareness on the part of the insurer (General Sick Fund) to embrace it and 'market' it.

Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

Science.gov (United States)

Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

2017-07-01

Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

Enhancing anticoagulation and endothelial cell proliferation of titanium surface by sequential immobilization of poly(ethylene glycol) and collagen

International Nuclear Information System (INIS)

Pan, Chang-Jiang; Hou, Yan-Hua; Ding, Hong-Yan; Dong, Yun-Xiao

2013-01-01

In the present study, poly(ethylene glycol) (PEG) and collagen I were sequentially immobilized on the titanium surface to simultaneously improve the anticoagulation and endothelial cell proliferation. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy analysis confirmed that PEG and collagen I were successfully immobilized on the titanium surface. Water contact angle results suggested the excellent hydrophilic surface after the immobilization. The anticoagulation experiments demonstrated that the immobilized PEG and collagen I on the titanium surface could not only obviously prevent platelet adhesion and aggregation but also prolong activated partial thromboplastin time (APTT), leading to the improved blood compatibility. Furthermore, immobilization of collagen to the end of PEG chain did not abate the anticoagulation. As compared to those on the pristine and PEG-modified titanium surfaces, endothelial cells exhibited improved proliferative profiles on the surface modified by the sequential immobilization of PEG and collagen in terms of CCK-8 assay, implying that the modified titanium may promote endothelialization without abating the blood compatibility. Our method may be used to modify the surface of blood-contacting biomaterials such as titanium to promote endothelialization and improve the anticoagulation, it may be helpful for development of the biomedical devices such as coronary stents, where endothelializaton and excellent anticoagulation are required.

Anticoagulant Prairie Dog Bait Risk Mitigation Measures to Protect Endangered Species

Science.gov (United States)

This Web page contains information on how certified pesticide applicators can use anticoagulant prairie dog bait products such as Rozol and Kaput-D while minimizing exposure risks to listed and non-target species.

Use of Non-Vitamin K Antagonist Oral Anticoagulants 2008-2016

DEFF Research Database (Denmark)

Haastrup, Simone; Hellfritzsch, Maja; Rasmussen, Lotte

2018-01-01

We aimed to provide detailed utilization data on the total use of non-vitamin K antagonist oral anticoagulants (NOACs) since their introduction in 2008. Using the nationwide Danish National Prescription Registry, we identified all individuals filling prescriptions for NOACs 2008-2016. We reported...

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

Stratifying the risks of oral anticoagulation in patients with liver disease.

Science.gov (United States)

Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

2014-05-01

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American

Investigation of contrast agent dosage for perfusion-weighted MRI

International Nuclear Information System (INIS)

Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

1997-01-01

Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

The recent clinical trials on use of the novel direct oral anticoagulants in patients with venous thromboembolism: a review

Directory of Open Access Journals (Sweden)

Gualtiero Palareti

2014-10-01

Full Text Available Venous thromboembolism (VTE, encompassing deep vein thrombosis and pulmonary embolism, requires an immediate anticoagulation, that has been carried out so far by administering a parenteral anticoagulant drug (heparin or derivatives overlapped with an oral vitamin K antagonist (VKA, more often warfarin. Several new direct oral anticoagulants (DOACs, with a mechanism of action completely different than VKA, have been developed in recent years. Recent clinical trials have investigated their use in VTE patients showing results at least equal for efficacy and safety, and sometime even better, as the standard anticoagulant treatment. There are differences in the design of the trials. In two cases the involved DOAC was administered immediately after VTE diagnosis as a single drug treatment (rivaroxaban and apixaban, whereas in the other trials (involving dabigatran and edoxaban the DOAC was administered after an initial course of approximately 7 days with heparin or derivatives. Some clinical trials have also investigated the use of DOACs for extended anticoagulant treatment after the acute phase. Aim of this article is to review the results of the currently available clinical trials that have compared the use of DOACs versus the standard of care in patients with VTE.

Na2EDTA anticoagulant impaired blood samples from the teleost Piaractus mesopotamicus

Directory of Open Access Journals (Sweden)

Thaís Heloisa Vaz Farias

2016-05-01

Full Text Available Abstract: The present study aimed to evaluate the effects of Na heparin and Na2EDTA on blood of Piaractus mesopotamicus (360.7±42.4g, 26.4±1.0cm. Twenty fishes were sampled in two experiment trials, ten for erythrocyte fragility analysis and ten for hematologic and plasma biochemical study. The blood collected by venous-caudal puncture was fractioned and stored in anticoagulants solution: Na2EDTA 10%, Na2EDTA 3%, Na heparin 5000 IU and Na heparin 100 IU. Plasmatic levels of calcium presented in the Na2EDTA stored samples were about 80% lower than both heparin groups. Blood samples of P. mesopotamicus stored with Na2EDTA demonstrated increase in the hematocrit and MCV, and decrease in MCHC. The dose-response effect was observed in this study. The results are reinforced by the higher levels of plasmatic protein and hemolysis presented in the Na2EDTA 10% stored blood, confirming the deleterious effect of this anticoagulant treatment on the quality of blood samples. Na2EDTA is not indicated to store P. mesopotamicus blood samples, but sodium heparin at 100 IU is the most recommended anticoagulant, since this treatment presented the lower rate of alterations in the stored blood.

[Pathogenesis and Laboratory Findings in Antiphospholipid Syndrome, Especially Associated with Lupus Anticoagulant].

Science.gov (United States)

Ieko, Masahiro; Naito, Sumiyoshi; Yoshida, Mika; Takahashi, Nobuhiko

2015-10-01

Antiphospholipid syndrome (APS), an acquired thrombotic condition, is a complex clinical state characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Revised APS classification criteria are used for diagnosis, which include at least one clinical criterion (thrombosis or pregnancy loss) and at least one of the laboratory criteria [anticardiolipin antibodies, anti-β2GPI antibodies, lupus anticoagulant (LA)]. LA is also an independent risk factor for developing thrombosis, though some LA-positive cases have been reported to have a bleeding symptom. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disorder characterized by a bleeding tendency due to low prothrombin activity in patients with LA, and has recently been reported not only in children but also in adults We have encountered LA cases with bleeding and low coagulation factor activities except for prothrombin. Based on our findings, we propose that LA-positive cases with a bleeding symptom and characterized by low coagulation factor activity including prothrombin be termed lupus anticoagulant-associated coagulopathy (LAAC). Furthermore, coagulation factor autoantibodies are often detected in LAAC patients; thus, correct measurement of LA is important to distinguish LAAC patients from those possessing an inhibitor to coagulation factors such as acquired hemophilia A as well as to select the optimal therapeutic strategy.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

Science.gov (United States)

Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

2015-12-01

A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Management of anticoagulation in hip fractures: A pragmatic approach.

Science.gov (United States)

Yassa, Rafik; Khalfaoui, Mahdi Yacine; Hujazi, Ihab; Sevenoaks, Hannah; Dunkow, Paul

2017-09-01

Hip fractures are common and increasing with an ageing population. In the United Kingdom, the national guidelines recommend operative intervention within 36 hours of diagnosis. However, long-term anticoagulant treatment is frequently encountered in these patients which can delay surgical intervention. Despite this, there are no set national standards for management of drug-induced coagulopathy pre-operatively in the context of hip fractures.The aim of this study was to evaluate the management protocols available in the current literature for the commonly encountered coagulopathy-inducing agents.We reviewed the current literature, identified the reversal agents used in coagulopathy management and assessed the evidence to determine the optimal timing, doses and routes of administration.Warfarin and other vitamin K antagonists (VKA) can be reversed effectively using vitamin K with a dose in the range of 2 mg to 10 mg intravenously to correct coagulopathy.The role of fresh frozen plasma is not clear from the current evidence while prothrombin complex remains a reliable and safe method for immediate reversal of VKA-induced coagulopathy in hip fracture surgery or failed vitamin K treatment reversal.The literature suggests that surgery should not be delayed in patients on classical antiplatelet medications (aspirin or clopidogrel), but spinal or regional anaesthetic methods should be avoided for the latter. However, evidence regarding the use of more novel antiplatelet medications (e.g. ticagrelor) and direct oral anticoagulants remains a largely unexplored area in the context of hip fracture surgery. We suggest treatment protocols based on best available evidence and guidance from allied specialties.Hip fracture surgery presents a common management dilemma where semi-urgent surgery is required. In this article, we advocate an evidence-based algorithm as a guide for managing these anticoagulated patients. Cite this article: EFORT Open Rev 2017;2:394-402. DOI: 10.1302/2058-5241.2.160083.

Concurrent use of tramadol and oral vitamin K antagonists and the risk of excessive anticoagulation

DEFF Research Database (Denmark)

Pottegård, Anton; Meegaard, P. M.; Holck, L. H.

2013-01-01

.9-5.2). This corresponds to, on average, one excess case per 250 treatment years (CI 125-584). The result is potentially confounded by concomitant paracetamol use and the presence of acute illness. CONCLUSION: Caution is advised when using tramadol in patients using VKA, and if possible, an alternative pain......OBJECTIVES: The objective was to assess whether the concurrent use of tramadol and vitamin K antagonists (VKAs) leads to an increased risk of excessive anticoagulation. DESIGN: The study was designed as a case-control study, nested within users of VKA and with tramadol use as our main exposure. We...... anticoagulation attributable to the use of tramadol. RESULTS: A total of 178 patients were included, 30 of which were exposed to tramadol, along with 2643 controls, 114 of which were exposed to tramadol. The adjusted odds-ratio for experiencing excessive anticoagulation during use of tramadol was 3.1 (1...

Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants.

Science.gov (United States)

Moustafa, Farès; Pesavento, Raffaele; di Micco, Pierpaolo; González-Martínez, José; Quintavalla, Roberto; Peris, Maria-Luisa; Porras, José Antonio; Falvo, Nicolas; Baños, Pilar; Monreal, Manuel

2018-04-01

We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Anticoagulant use for the prevention of stroke in patients with atrial fibrillation: findings from a multi-payer analysis.

Science.gov (United States)

Lang, Kathleen; Bozkaya, Duygu; Patel, Aarti A; Macomson, Brian; Nelson, Winnie; Owens, Gary; Mody, Samir; Schein, Jeff; Menzin, Joseph

2014-07-28

Oral anticoagulation is recommended for stroke prevention in intermediate/high stroke risk atrial fibrillation (AF) patients. The objective of this study was to demonstrate the usefulness of analytic software tools for descriptive analyses of disease management in atrial AF; a secondary objective is to demonstrate patterns of potential anticoagulant undertreatment in AF. Retrospective data analyses were performed using the Anticoagulant Quality Improvement Analyzer (AQuIA), a software tool designed to analyze health plan data. Two-year data from five databases were analyzed: IMS LifeLink (IMS), MarketScan Commercial (MarketScanCommercial), MarketScan Medicare Supplemental (MarketScanMedicare), Clinformatics™ DataMart, a product of OptumInsight Life Sciences (Optum), and a Medicaid Database (Medicaid). Included patients were ≥ 18 years old with a new or existing diagnosis of AF. The first observed AF diagnosis constituted the index date, with patient outcomes assessed over a one year period. Key study measures included stroke risk level, anticoagulant use, and frequency of International Normalized Ratio (INR) monitoring. High stroke risk (CHADS2 ≥ 2 points) was estimated in 54% (IMS), 22% (MarketScanCommercial), 64% (MarketscanMedicare), 42% (Optum) and 62% (Medicaid) of the total eligible population. Overall, 35%, 29%, 38%, 39% and 16% of all AF patients received an anticoagulant medication in IMS, MarketScanCommercial, MarketScanMedicare, Optum and Medicaid, respectively. Among patients at high risk for stroke, 19% to 51% received any anticoagulant. The AQuIA provided a consistent platform for analysis across multiple AF populations with varying baseline characteristics. Analyzer results show that many high-risk AF patients in selected commercial, Medicare-eligible, and Medicaid populations do not receive appropriate thromboprophylaxis, as recommended by treatment guidelines.

Cross-cultural adaptation and psychometric properties of the Brazilian-Portuguese version of the Duke Anticoagulation Satisfaction Scale.

Science.gov (United States)

Pelegrino, Flávia M; Dantas, Rosana A S; Corbi, Inaiara S A; da Silva Carvalho, Ariana R; Schmidt, André; Pazin Filho, Antônio

2012-09-01

The aim of this study was to evaluate the internal reliability and validity of the Brazilian-Portuguese version of Duke Anticoagulation Satisfaction Scale (DASS) among cardiovascular patients. Oral anticoagulation is widely used to prevent and treat thromboembolic events in several conditions, especially in cardiovascular diseases; however, this therapy can induce dissatisfaction and reduce the quality of life. Methodological and cross-sectional research design. The cultural adaptation of the DASS included the translation and back-translation, discussions with healthcare professionals and patients to ensure conceptual equivalence, semantic evaluation and instrument pretest. The Brazilian-Portuguese version of the DASS was tested among subjects followed in a university hospital anticoagulation outpatient clinic. The psychometric properties were assessed by construct validity (convergent, known groups and dimensionality) and internal consistency/reliability (Cronbach's alpha). A total of 180 subjects under oral anticoagulation formed the baseline validation population. DASS total score and SF-36 domain correlations were moderate for General health (r=-0.47, pDASS score and most of the subscales, except Limitation (r=-0.375, pscale, and it ranged from 0.76 (hassles and burdens)-0.46 (psychological impact) among the domains, confirming the internal consistency reliability. The Brazilian-Portuguese version of the DASS has shown levels of reliability and validity comparable with the original English version. Healthcare practitioners and researchers need internationally validated measurement tools to compare outcomes of interventions in clinical management and research tools in oral anticoagulation therapy. © 2011 Blackwell Publishing Ltd.

The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity.

LENUS (Irish Health Repository)

Preston, Roger J S

2012-02-01

We report a kindred with heritable protein C (PC) deficiency in which two siblings with severe thrombosis showed a composite type I and IIb PC deficiency phenotype, identified using commercial PC assays (proband: PC antigen 42 u\\/dl, amidolytic activity 40 u\\/dl, anticoagulant activity 9 u\\/dl). The independent PROC nucleotide variations c.669C>A (predictive of Ser181Arg) and c.131C>T (predictive of Asn2Ile) segregated with the type I and type IIb PC deficiency phenotypes respectively, but co-segregated in the siblings with severe thrombosis. Soluble thrombomodulin (sTM)-mediated inhibition of plasma thrombin generation from an individual with PC-Asn2Ile was lower (endogenous thrombin potential (ETP) 56 +\\/- 1% that of ETP determined without sTM) than control plasma (ETP 15 +\\/- 2%) indicating reduced PC anticoagulant activity. Recombinant APC-Asn2Ile exhibited normal amidolytic activity but impaired anticoagulant activity. Protein S (PS)-dependent anticoagulant activity of recombinant APC-Asn2Ile and binding of recombinant APC-Asn2Ile to endothelial protein C receptor (EPCR) were reduced compared to recombinant wild-type APC. Asn2 lies within the omega-loop of the PC\\/APC Gla domain and this region is critical for calcium-induced folding and subsequent interactions with anionic phospholipids, EPCR and PS. The disruption of these interactions in this naturally-occurring PC variant highlights their collective importance in mediating APC anticoagulant activity in vivo.

Anticoagulation: Where have we come from and where are we going ...

African Journals Online (AJOL)

is its predictable renal excretion, with low inter- and intra-individual variability.[11] Clinically, this ... recent meta-analysis of 50 000 patients requiring anticoagulation ... data supporting the use of NOACs in secondary stroke prevention in. NVAF.

Initiation of anticoagulation in atrial fibrillation

DEFF Research Database (Denmark)

Gundlund, A.; Staerk, L.; Fosbøl, E. L.

2017-01-01

Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Methods: Using Danish nationwide registry data, we...... compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28–1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67–0.77). Conclusions: Atrial fibrillation patients who were initiated...

Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement.

Science.gov (United States)

Del Trigo, María; Muñoz-García, Antonio J; Latib, Azeem; Auffret, Vincent; Wijeysundera, Harindra C; Nombela-Franco, Luis; Gutierrez, Enrique; Cheema, Asim N; Serra, Vicenç; Amat-Santos, Ignacio J; Kefer, Joelle; Benitez, Luis Miguel; Leclercq, Florence; Mangieri, Antonio; Le Breton, Hervé; Jiménez-Quevedo, Pilar; Garcia Del Blanco, Bruno; Dager, Antonio; Abdul-Jawad Altisent, Omar; Puri, Rishi; Pibarot, Philippe; Rodés-Cabau, Josep

2018-05-01

To evaluate the changes in transvalvular gradients and the incidence of valve haemodynamic deterioration (VHD) following transcatheter aortic valve replacement (TAVR), according to use of anticoagulation therapy. This multicentre study included 2466 patients (46% men; mean age 81±7 years) who underwent TAVR with echocardiography performed at 12-month follow-up. Anticoagulation therapy was used in 707 patients (28.7%) following TAVR (AC group). A total of 663 patients received vitamin K antagonists, and 44 patients received direct oral anticoagulants. A propensity score matching analysis was performed to adjust for intergroup (AC vs non-AC post-TAVR) differences. A total of 622 patients per group were included in the propensity-matched analysis. VHD was defined as a ≥10 mm Hg increase in the mean transprosthetic gradient at follow-up (vs hospital discharge). The mean clinical follow-up was 29±18 months. The mean transvalvular gradient significantly increased at follow-up in the non-AC group within the global cohort (P=0.003), whereas it remained stable over time in the AC group (P=0.323). The incidence of VHD was significantly lower in the AC group (0.6%) compared with the non-AC group (3.7%, P<0.001), and these significant differences remained within the propensity-matched populations (0.6% vs 3.9% in the AC and non-AC groups, respectively, P<0.001). The occurrence of VHD did not associate with an increased risk of all-cause death (P=0.468), cardiovascular death (P=0.539) or stroke (P=0.170) at follow-up. The lack of anticoagulation therapy post-TAVR was associated with significant increments in transvalvular gradients and a greater risk of VHD. VHD was subclinical in most cases and did not associate with major adverse clinical events. Future randomised trials are needed to determine if systematic anticoagulation therapy post-TAVR would reduce the incidence of VHD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

Science.gov (United States)

Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

1996-09-01

Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

Energy Technology Data Exchange (ETDEWEB)

Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

International Nuclear Information System (INIS)

Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

1982-01-01

A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

Inhibition of adhesion breast cancer cells by anticoagulant drugs and cimetidine

Czech Academy of Sciences Publication Activity Database

Bobek, V.; Boubelík, Michael; Kovařík, J.; Taltynov, O.

2003-01-01

Roč. 50, č. 2 (2003), s. 148-151 ISSN 0028-2685 Institutional research plan: CEZ:AV0Z5052915 Keywords : cimetidine * breast cancer * anticoagulants Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.782, year: 2003

Percutaneous left atrial appendage occlusion in atrial fibrillation patients with a contraindication to oral anticoagulation: a focused review.

Science.gov (United States)

Nishimura, Marin; Sab, Shiv; Reeves, Ryan R; Hsu, Jonathan C

2017-12-08

Stroke is the most feared complication of atrial fibrillation (AF). Although oral anticoagulation with non-vitamin K antagonist and non-vitamin K antagonist oral anticoagulants (NOACs) have been established to significantly reduce risk of stroke, real-world use of these agents are often suboptimal due to concerns for adverse events including bleeding from both patients and clinicians. Particularly in patients with previous serious bleeding, oral anticoagulation may be contraindicated. Left atrial appendage occlusion (LAAO), mechanically targeting the source of most of the thrombi in AF, holds an immense potential as an alternative to OAC in management of stroke prophylaxis. In this focused review, we describe the available evidence of various LAAO devices, detailing data regarding their use in patients with a contraindication for oral anticoagulation. Although some questions of safety and appropriate use of these new devices in patients who cannot tolerate anticoagulation remain, LAAO devices offer a significant step forward in the management of patients with AF, including those patients who may not be able to be prescribed OAC at all. Future studies involving patients fully contraindicated to OAC are warranted in the era of LAAO devices for stroke risk reduction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Synthesis and in Vitro and in Vivo Anticoagulant and Antiplatelet Activities of Amidino- and Non-Amidinobenzamides

Directory of Open Access Journals (Sweden)

Soo Hyun Lee

2016-05-01

Full Text Available Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1–13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin time (aPTT and prothrombin time (PT in vitro. From the aPTT results obtained, two amidinobenzamides, N-(3′-amidinophenyl-3-(thiophen-2′′-ylcarbonylamino benzamide (1, 33.2 ± 0.7 s and N-(4′-amidinophenyl-3-(thiophen-2′′-ylcarbonylamino benzamide (2, 43.5 ± 0.6 s were selected to investigate the further anticoagulant and antiplatelet activities. The aPTT results of 1 (33.2 ± 0.7 s and 2 (43.5 ± 0.6 s were compared with heparin (62.5 ± 0.8 s in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity (ex vivo and on tail bleeding time (in vivo on mice. A tail cutting/bleeding time assay revealed that both 1 and 2 prolonged bleeding time in mice at a dose of 24.1 g/mouse and above. Compounds 1 and 2 dose-dependently inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In addition, 1 and 2 were evaluated on the inhibitory activities of thrombin and FXa as well as the generation of thrombin and FXa in human umbilical vein endothelial cells (HUVECs. Collectively, 1 and 2 possess some antiplatelet and anticoagulant activities and offer a basis for development of a novel antithrombotic product.

Improved circulating microparticle analysis in acid-citrate dextrose (ACD) anticoagulant tube.

Science.gov (United States)

György, Bence; Pálóczi, Krisztina; Kovács, Alexandra; Barabás, Eszter; Bekő, Gabriella; Várnai, Katalin; Pállinger, Éva; Szabó-Taylor, Katalin; Szabó, Tamás G; Kiss, Attila A; Falus, András; Buzás, Edit I

2014-02-01

Recently extracellular vesicles (exosomes, microparticles also referred to as microvesicles and apoptotic bodies) have attracted substantial interest as potential biomarkers and therapeutic vehicles. However, analysis of microparticles in biological fluids is confounded by many factors such as the activation of cells in the blood collection tube that leads to in vitro vesiculation. In this study we aimed at identifying an anticoagulant that prevents in vitro vesiculation in blood plasma samples. We compared the levels of platelet microparticles and non-platelet-derived microparticles in platelet-free plasma samples of healthy donors. Platelet-free plasma samples were isolated using different anticoagulant tubes, and were analyzed by flow cytometry and Zymuphen assay. The extent of in vitro vesiculation was compared in citrate and acid-citrate-dextrose (ACD) tubes. Agitation and storage of blood samples at 37 °C for 1 hour induced a strong release of both platelet microparticles and non-platelet-derived microparticles. Strikingly, in vitro vesiculation related to blood sample handling and storage was prevented in samples in ACD tubes. Importantly, microparticle levels elevated in vivo remained detectable in ACD tubes. We propose the general use of the ACD tube instead of other conventional anticoagulant tubes for the assessment of plasma microparticles since it gives a more realistic picture of the in vivo levels of circulating microparticles and does not interfere with downstream protein or RNA analyses. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Comparison of quality and hemorragic risk of oral anticoagulant therapy using acenocoumarol versus warfarin].

Science.gov (United States)

Oliva Berini, Elvira; Galán Alvarez, Pilar; Pacheco Onrubia, Ana María

2008-06-21

Long half life oral anticoagulants have shown a higher anticoagulation stability and a lower hemorragic risk than those of a short half life. We have compared therapeutic stability and hemorragic risk of acenocoumarol versus warfarin in 2 groups of patients on preventive anticoagulation because of atrial fibrilation (international normalised ratio [INR]: 2-3). Data on 120 patients treated with acenocoumarol and 120 on warfarin treatment who had started and continued treatment in our hospital for a minimum of a year was collected. The percentage of visits within the intended range of INR (2 to 3) was 65.5% with warfarin and 63.4% with acenocoumarol. Thirty percent of patients on warfarin had 75% or more of their controls within range, while for those treated with acenocoumarol this percentage was 22.5%. In the acenocoumarol group, 0.3 visits/patient/year presented an INR > or = 6 versus 0.07 in the warfarin group (p = 0.003). Patients treated with acenocoumarol show a higher risk of presenting with an INR > or = 6, but no statistically significant differences are observed in therapeutic stability.

Anticoagulant resistance: a relevant issue in sewer rat (Rattus norvegicus) control?

DEFF Research Database (Denmark)

Heiberg, Ann-Charlotte

2009-01-01

the resistant rats, had resistance-related mutations in the VKORC1 gene. CONCLUSION: The results of this study suggest that the genetic background of anticoagulant resistance may have to be redefined in respect of resistance-related changes in the VKORC1 gene. Copyright © 2009 Society of Chemical Industry......BACKGROUND: The majority of rat problems in cities are thought to be related to defective sewers, and the use of anticoagulant rodenticides in such places is often implemented as part of regular urban rodent control. Knowledge pertaining to the resistance status of sewer rat populations is non......-existent, which may be leading to control problems in cities. It has become crucial to provide knowledge on the prevalence of resistance and how different control strategies have affected its prevalence among sewer rat populations. The prevalence of resistance was investigated in six sewer locations in Copenhagen...

Evolution of vertebrate sex chromosomes and dosage compensation.

Science.gov (United States)

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Quantitative method for analysis of six anticoagulant rodenticides in faeces, applied in a case with repeated samples from a dog.

Science.gov (United States)

Seljetun, Kristin Opdal; Eliassen, Elin; Karinen, Ritva; Moe, Lars; Vindenes, Vigdis

2018-01-17

Accidental poisoning with anticoagulant rodenticides is not uncommon in dogs, but few reports of the elimination kinetics and half-lives in this species have been published. Our objectives were to develop and validate a new method for the quantification of anticoagulant rodenticides in canine blood and faeces using reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and apply the method on a case of anticoagulant rodenticide intoxication. Sample preparation was liquid-liquid extraction. Six anticoagulant rodenticides were separated using a UPLC ® BEH C 18 -column with a mobile phase consisting of 5 mM ammonium formate buffer pH 10.2 and methanol. MS/MS detection was performed with positive electrospray ionization and two multiple reaction monitoring transitions. The limits of quantification were set at the levels of the lowest calibrator (1.5-2.7 ng/mL or ng/g). The method was successfully applied to a case from a dog accidentally poisoned with anticoagulant rodenticide. Coumatetralyl and brodifacoum concentrations were determined from serial blood and faecal samples. A terminal half-life of at least 81 days for coumatetralyl in blood was estimated, which is longer than previous reported in other species. A slow elimination of brodifacoum from the faeces was found, with traces still detectable in the faeces at day 513. This study offers a new method of detection and quantification of six frequently used anticoagulant rodenticides in canine faeces. Such drugs might cause serious health effects and it is important to be able to detect these drugs, to initiate proper treatment. The very long elimination half-lives detected in our study is important to be aware of in assessment of anticoagulant rodenticide burden to the environment.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus Vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation: A Meta-Analysis.

Directory of Open Access Journals (Sweden)

Giuseppe Santarpia

Full Text Available Use of the non-vitamin K antagonist oral anticoagulants (NOACs is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF. However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA of AF has not been well established yet.To perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs in patients undergoing RFCA.Studies were searched for in PubMed and Google Scholar databases.Studies were considered eligible if: they evaluated the clinical impact of NOACs versus VKAs; they specifically analyzed the use of anticoagulants during periprocedural phase of RFCA; they reported clinical outcome data.25 studies were selected, including 9881 cases. The summary measure used was the risk ratio (RR with 95% confidence interval (CI. The random-effects or the fixed effect model were used to synthesize results from the selected studies.There was no significant difference in thromboembolic complications (RR 1.39; p=0.13. Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001. Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns. In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002 and major bleeding (RR=0.41; p=0.01 events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02.As with every meta-analysis, no patients-level data were available.The use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no

Semi-solid dosage form of clonazepam for rapid oral mucosal absorption.

Science.gov (United States)

Sakata, Osamu; Machida, Yoshiharu; Onishi, Hiraku

2011-07-01

In order to obtain an alternative to the intravenous (i.v.) dosage form of clonazepam (CZ), an oral droplet formulation of CZ was developed previously; however, the droplet was physically unstable. Therefore, in the present study, it was attempted to develop an easily-handled dosage form, which was more physically stable and allowed rapid drug absorption from oral mucosa. A semi-solid dosage form, composed of polyethylene glycol 1500 (PEG), CZ, and oleic acid (OA) at 37/1/2 (w/w) and named PEG/CZ/OA, and a semi-solid dosage form containing PEG and CZ at 39/1 (w/w), called PEG/CZ, were prepared. Their physical stability in air at room temperature and oral mucosal absorption in rats were investigated. The semi-solid dosage forms were much more stable physically than the droplet, that is, no recrystallization of CZ was observed for at least 8 days. The effective concentration for humans and rats (20 ng/mL or more) was achieved within 30 min after buccal administration for both PEG/CZ/OA and PEG/CZ. The plasma concentration increased gradually and less varied at each time point for PEG/CZ/OA. PEG/CZ/OA was found to show more rapid and higher absorption of CZ in buccal administration than in sublingual administration. Buccal administration with the semi-solid dosage PEG/CZ with or without OA was suggested to be a possibly useful novel dosage form as an alternative to i.v. injection.

Feasibility Study of a Mobile Health Intervention for Older Adults on Oral Anticoagulation Therapy

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Jung-Ah Lee PhD, RN

2016-10-01

Full Text Available Background: Oral anticoagulation treatment (OAT such as warfarin therapy is recommended for older adults with atrial fibrillation, heart failure, or who are at risk for venous thromboembolism. Despite its proven benefits, older adults report both dissatisfaction with OAT and reduced quality of life that can potentially lead to low adherence to OAT and decreased treatment efficacy. Objective: To test the feasibility of Mobile Applications for Seniors to enhance Safe anticoagulation therapy (MASS, a mobile-based health technology intervention designed to promote independence and self-care. Method s: This pilot study used a single-arm experimental pre–post design to test the feasibility of a 3-month intervention using MASS in 18 older adults (male: n = 14; White: n = 9; Hispanic: n = 7; Other: n = 2; M age = 67. MASS was available in English or Spanish. Participants completed surveys about their OAT knowledge, attitudes, quality of life with OAT, and adherence at baseline and at a 3-month follow-up. Satisfaction with the MASS intervention was also assessed at follow-up. Results: Anticoagulation knowledge significantly improved from baseline to follow-up ( M base = 12.5 ± 5.51, M follow-up = 14.78 ± 3.93, p = .007. Other outcomes were not different, pre- and post-tests. Participants reported they were generally satisfied with MASS, its ease of use and its usefulness. Conclusion: The results showed use of MASS improved older adults’ knowledge of OAT. Using mHealth apps may enhance self-care among older adults with chronic conditions who are also taking oral anticoagulants.

Evaluation of insecticides in different dosages to control cicadas in parica plantations

Directory of Open Access Journals (Sweden)

Odineila Martins Monteiro

2014-07-01

Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs Versus Direct Oral Anticoagulants (DOACs

Directory of Open Access Journals (Sweden)

Rick H. van Gorp

2015-11-01

Full Text Available Vitamin K-antagonists (VKA are the most widely used anticoagulant drugs to treat patients at risk of arterial and venous thrombosis for the past 50 years. Due to unfavorable pharmacokinetics VKA have a small therapeutic window, require frequent monitoring, and are susceptible to drug and nutritional interactions. Additionally, the effect of VKA is not limited to coagulation, but affects all vitamin K-dependent proteins. As a consequence, VKA have detrimental side effects by enhancing medial and intimal calcification. These limitations stimulated the development of alternative anticoagulant drugs, resulting in direct oral anticoagulant (DOAC drugs, which specifically target coagulation factor Xa and thrombin. DOACs also display non-hemostatic vascular effects via protease-activated receptors (PARs. As atherosclerosis is characterized by a hypercoagulable state indicating the involvement of activated coagulation factors in the genesis of atherosclerosis, anticoagulation could have beneficial effects on atherosclerosis. Additionally, accumulating evidence demonstrates vascular benefit from high vitamin K intake. This review gives an update on oral anticoagulant treatment on the vasculature with a special focus on calcification and vitamin K interaction.

Discontinuation risk comparison among 'real-world' newly anticoagulated atrial fibrillation patients

DEFF Research Database (Denmark)

Lip, Gregory Y H; Pan, Xianying; Kamble, Shital

2018-01-01

Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran,...

Recommendations for the anticoagulation of pregnant patients with mechanical heart valves

NARCIS (Netherlands)

Schapkaitz, Elise; Jacobson, Barry Frank; Manga, Pravin; Chitsike, Rufaro Saeed; Benade, Estee; Haas, Sylvia; Buller, Harry R.

2015-01-01

The management of pregnant patients with mechanical heart valves remains challenging because there are no large randomised studies to provide guidelines for effective anticoagulant therapy. Both vitamin K antagonists and heparins may be associated with maternal and foetal adverse events. The

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

21 CFR 330.3 - Imprinting of solid oral dosage form drug products.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Imprinting of solid oral dosage form drug products... AS SAFE AND EFFECTIVE AND NOT MISBRANDED General Provisions § 330.3 Imprinting of solid oral dosage form drug products. A requirement to imprint an identification code on solid oral dosage form drug...

Outcome after discontinuing anticoagulant therapy in women with venous thromboembolism during hormonal use.

Science.gov (United States)

Blanco-Molina, Ángeles; Trujillo-Santos, Javier; Pesavento, Raffaele; Rosa, Vladimir; Falgá, Conxita; Tolosa, Carles; Mazzolai, Lucia; Sampériz, Ángel; Duce, Rita; Monreal, Manuel

2017-03-01

Whether women developing venous thromboembolism (VTE) while using hormonal therapy should be classified as having "unprovoked" or "provoked" VTE is controversial. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic VTE recurrences after discontinuing anticoagulation in 3 subgroups of women aged ≤50years without cancer, pregnancy or puerperium: (1) those with hormonal therapy and no additional risk factors (hormonal users only); (2) those with unprovoked VTE; and (3) those with additional risk factors, with or without hormonal therapy. As of March 2016, 1513 women had been followed-up for at least one month after discontinuing anticoagulation. Of these, 654 (43%) were hormonal users only, 390 (26%) had unprovoked VTE and 469 (31%) had transient risk factors with or without hormonal therapy. After discontinuing anticoagulation, the rate of VTE recurrences in women with hormonal use only (2.44 per 100 patient-years; 95% CI: 1.53-3.69) was significantly lower than in those with unprovoked VTE (6.03; 95% CI: 3.97-8.77) and similar to those with transient risk factors (2.58; 95% CI: 1.50-4.13). Interestingly, the rate of VTE recurrences presenting as pulmonary embolism in women with hormonal use only (0.55 per 100 patient-years; 95% CI: 0.18-1.29) was similar to those with transient risk factors (0.46; 95% CI: 0.09-1.33) and 4-fold lower than in women with unprovoked VTE (2.23; 95% CI: 1.07-4.10). After discontinuing anticoagulation, the rate of VTE recurrences in hormonal users only was significantly lower than in women with unprovoked VTE and similar to the rate in women with additional risk factors. © 2017 Elsevier Ltd. All rights reserved.

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

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Qian Li

Full Text Available BACKGROUND: Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. METHODOLOGY: We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671 between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. CONCLUSIONS: This article proposes a network-based multi-target computational estimation

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

Science.gov (United States)

Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-03-22

Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by

Tailoring of TiO2 films by H2SO4 treatment and UV irradiation to improve anticoagulant ability and endothelial cell compatibility.

Science.gov (United States)

Liao, Yuzhen; Li, Linhua; Chen, Jiang; Yang, Ping; Zhao, Ansha; Sun, Hong; Huang, Nan

2017-07-01

Surfaces with dual functions that simultaneously exhibit good anticoagulant ability and endothelial cell (EC) compatibility are desirable for blood contact materials. However, these dual functions have rarely been achieved by inorganic materials. In this study, titanium dioxide (TiO 2 ) films were treated by sulphuric acid (H 2 SO 4 ) and ultraviolet (UV) irradiation successively (TiO 2 H 2 SO 4 -UV), resulting in good anticoagulant ability and EC compatibility simultaneously. We found that UV irradiation improved the anticoagulant ability of TiO 2 films significantly while enhancing EC compatibility, though not significantly. The enhanced anticoagulant ability could be related to the oxidation of surface-adsorbed hydrocarbons and increased hydrophilicity. The H 2 SO 4 treatment improved the anticoagulant ability of TiO 2 films slightly, while UV irradiation improved the anticoagulant ability strongly. The enhanced EC compatibility could be related to the increased surface roughness and positive charges on the surface of the TiO 2 films. Furthermore, the time-dependent degradation of the enhanced EC compatibility and anticoagulant ability of TiO 2 H 2 SO 4 -UV was observed. In summary, TiO 2 H 2 SO 4 -UV expressed both excellent anticoagulant ability and good EC compatibility at the same time, which could be desirable for blood contact materials. However, the compatibility of TiO 2 H 2 SO 4 -UV with smooth muscle cells (SMCs) and macrophages was also improved. More effort is still needed to selectively improve EC compatibility on TiO 2 films for better re-endothelialization. Copyright © 2017 Elsevier B.V. All rights reserved.

The impact of pre-injury anticoagulation therapy in the older adult patient experiencing a traumatic brain injury: A systematic review.

Science.gov (United States)

Smith, Karen; Weeks, Susan

2012-01-01

The objective of this systematic review is to synthesize the best available evidence on the impact of pre-injury anticoagulation therapy in the older adult patient who experiences a traumatic brain injury. Trauma in the elderly remains one of the most challenging problems for healthcare providers in the 21 century. The most recent United States (U.S.) census estimates that by the year 2020 more than 52 million Americans will be age 65 years or older, and one million of those will live to be over 100 years of age. In the older adult population, classified as age 65 years or greater, the two leading causes of injury were reported as motor vehicle crashes (MVC) and falls. We have become increasingly aware of the unique physiologic changes in this population that make them more susceptible to succumb to traumatic injuries than their younger counterparts. This is especially true in the anticoagulated patient with a traumatic brain injury.Traumatic brain injury (TBI) is defined as an injury occurring when an external force traumatizes the brain. It may also be known as an intracranial or head injury. TBI is classified depending on the mechanism of injury (blunt or penetrating), severity, and location of the assault. Damage to the brain, skull, and/or scalp transpires. TBI is the leading cause of death and disability in the U.S, and persons of all ages, races, ethnicities, and incomes are affected. In the past five to ten years, trauma services have recorded an increase in major trauma admissions of patients age 65 years and older. In review of the literature to date, it is recognized that outcomes following moderate to severe TBI in older adults are poor, with high rates of significant disability and mortality reported. A recent Australian study reported that 28% of older adults died in the hospital following a TBI and in Finland adults aged 75 years and older had the highest rates of TBI related hospitalizations and death. According to a systematic review of European

Automatic identification and normalization of dosage forms in drug monographs

Science.gov (United States)

2012-01-01

Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

Andexanet alfa effectively reverses edoxaban anticoagulation effects and associated bleeding in a rabbit acute hemorrhage model

Science.gov (United States)

Lu, Genmin; Pine, Polly; Leeds, Janet M.; DeGuzman, Francis; Pratikhya, Pratikhya; Lin, Joyce; Malinowski, John; Hollenbach, Stanley J.; Curnutte, John T.

2018-01-01

Introduction Increasing use of factor Xa (FXa) inhibitors necessitates effective reversal agents to manage bleeding. Andexanet alfa, a novel modified recombinant human FXa, rapidly reverses the anticoagulation effects of direct and indirect FXa inhibitors. Objective To evaluate the ability of andexanet to reverse anticoagulation in vitro and reduce bleeding in rabbits administered edoxaban. Materials and methods In vitro studies characterized the interaction of andexanet with edoxaban and its ability to reverse edoxaban-mediated anti-FXa activity. In a rabbit model of surgically induced, acute hemorrhage, animals received edoxaban vehicle+andexanet vehicle (control), edoxaban (1 mg/kg)+andexanet vehicle, edoxaban+andexanet (75 mg, 5-minute infusion, 20 minutes after edoxaban), or edoxaban vehicle+andexanet prior to injury. Results Andexanet bound edoxaban with high affinity similar to FXa. Andexanet rapidly and dose-dependently reversed the effects of edoxaban on FXa activity and coagulation pharmacodynamic parameters in vitro. In edoxaban-anticoagulated rabbits, andexanet reduced anti-FXa activity by 82% (from 548±87 to 100±41 ng/ml; P<0.0001), mean unbound edoxaban plasma concentration by ~80% (from 100±10 to 21±6 ng/ml; P<0.0001), and blood loss by 80% vs. vehicle (adjusted for control, 2.6 vs. 12.9 g; P = 0.003). The reduction in blood loss correlated with the decrease in anti-FXa activity (r = 0.6993, P<0.0001) and unbound edoxaban (r = 0.5951, P = 0.0035). Conclusion These data demonstrate that andexanet rapidly reversed the anticoagulant effects of edoxaban, suggesting it could be clinically valuable for the management of acute and surgery-related bleeding. Correlation of blood loss with anti-FXa activity supports the use of anti-FXa activity as a biomarker for assessing anticoagulation reversal in clinical trials. PMID:29590221

Dental Procedures in Patients with Atrial Fibrillation and New Oral Anticoagulants

Science.gov (United States)

2014-01-01

This review discusses the basic pharmacology of new oral anticoagulants that are used for prevention of thromboembolism in patients with atrial fibrillation. It presents available evidence, and provides recommendations for the management of patients requiring invasive procedures in dental practice. PMID:26835072

Evaluation of the effect of torsemide on warfarin dosage requirements.

Science.gov (United States)

Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

2017-08-01

Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

Managing direct oral anticoagulants in patients undergoing dentoalveolar surgery.

Science.gov (United States)

Patel, J P; Woolcombe, S A; Patel, R K; Obisesan, O; Roberts, L N; Bryant, C; Arya, R

2017-02-24

Our objective was to describe our experience of managing a cohort of adult patients prescribed direct oral anticoagulants (DOACs) undergoing dentoalveolar procedures between November 2012 and May 2016. Prior to conducting a procedure a formal assessment was made of each patient's anticoagulation treatment. A specific plan was then formulated, balancing the risk of bleeding with the risk of thrombosis. Patients received a telephone consultation one week following treatment to assess any post-operative bleeding. Eighty-two patients underwent 111 oral surgical procedures, the majority of which were dental extractions. In the case of 35 (32%) procedures, advice was given to omit the DOAC, either before or after treatment. There was no bleeding following the majority of procedures. Persistent bleeding followed 15 (13.5%) procedures, of which 7 (6.3%) procedures required specific intervention. The majority of patients prescribed DOACs can undergo dentoalveolar procedures safely. Important considerations when planning treatment are: (i) when the patient usually takes their dose of DOAC, (ii) the time the procedure is performed and, (iii) when the DOAC is taken post-procedure. In our experience, if these factors are considered carefully, omission of DOAC doses is unlikely to be required for most patients.

Haemorrhage in the labyrinth caused by anticoagulant therapy: case report

International Nuclear Information System (INIS)

Callonnec, F.; Gerardin, E.; Thiebot, J.; Marie, J.P.; Andrieu Guitrancourt, J.; Marsot-Dupuch, K.

1999-01-01

We report a patient who experienced a severe vertiginous episode with bilateral tinnitus and progressive right-sided hearing loss. She had Marfan's disease and was on anticoagulant treatment. The fluid in the labyrinth gave higher signal than cerebrospinal fluid on T1-weighted images, suggesting haemorrhage. The radiological follow-up is discussed. (orig.)

Portuguese Observational Study of Ischaemic Stroke in Patients Medicated with Non-Vitamin K Antagonist Oral Anticoagulants.

Science.gov (United States)

Beato-Coelho, José; Marto, João Pedro; Alves, José Nuno; Marques-Matos, Cláudia; Calado, Sofia; Araújo, José; Cunha, Luís; Pinho, João; Azevedo, Elsa; Viana-Baptista, Miguel; Sargento-Freitas, João

2018-01-01

Clinical trials and subsequent meta-analyses showed advantages of non-vitamin K antagonists oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation. The impact of preadmission anticoagulation in acute ischaemic stroke (AIS) has not been established. To compare functional outcome of patients with AIS with preadmission NOACs vs. VKAs. A retrospective analysis was conducted on consecutive AIS patients under oral anticoagulation (VKAs or NOACs) admitted in 4 Portuguese hospitals within a period of 30 months. Two primary outcomes were defined and compared between VKA and NOAC groups: symptomatic intracerebral hemorrhage transformation (sICH) and modified Rankin Scale (mRS) at 3 months. Four hundred sixty-nine patients were included, of whom 332 (70.8%) were treated with VKA and 137 (29.2%) with NOAC. Patients' median age was 78.0 and 234 (49.9%) were male. NOAC-treated patients had a higher median CHA2DS2-VASc score than those under VKA (5.0 vs. 4.0, p = 0.023). The two primary outcomes showed no statistical differences between the VKAs' group and the NOACs' group (sICH: 5.4 vs. 5.4% [p = 0.911]; mRS at 3 months: 3.0 vs. 3.0 [p = 0.646], respectively). Preadmission anticoagulation with NOACs in AIS has a functional impact similar to that of VKAs. © 2018 S. Karger AG, Basel.

Anticoagulation After Biological Aortic Valve Replacement: Is There An Optimal Regimen?

Science.gov (United States)

Owais, Tamer; Rouman, Mina; Breuer, Martin; Hüter, Lars; Fuchs, Jürgen; Lauer, Bernward; Kuntze, Thomas

2016-03-01

The anticoagulation of biological heart valves remains a 'hot spot' of discussion in various domains due to the risk of developing valve thrombosis and arterial thromboembolism. The situation has always been controversial, especially during the early postoperative phase. The American College of Cardiology/ American Heart Association and European Society of Cardiology guidelines recommend the use of warfarin for the first three months after biological aortic valve replacement (BAVR), although the American College of Chest Physicians guidelines suggest that these recommendations are experience-based and that the risk/benefit is unclear. The aim of the present study was to compare the efficacy of aspirin and warfarin in patients after BAVR. A total of 863 patients who underwent BAVR between 2008 and 2015 was allocated to two groups. Each group was managed with a specific anticoagulation regimen, with 430 patients receiving warfarin during the first three postoperative months, and 433 receiving aspirin. The major study end points were bleeding, cerebral ischemic events, and survival. In total, 10 and 15 postoperative cerebral ischemic events occurred between 24 h and three months after surgery in patients treated with aspirin and warfarin, respectively. After three months the incidence of cerebral ischemic events did not differ greatly between the two groups. The rate of major bleeding events and rates of stroke-free survival and overall survival were not statistically significant between the warfarin and aspirin groups. Plasma anticoagulation with warfarin during the early postoperative phase was shown statistically to be inferior to platelet aggregation inhibition by aspirin with regards to postoperative bleeding risk, cerebral ischemic events, and survival.

Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

NARCIS (Netherlands)

Diener, H.C.; Aisenberg, J.; Ansell, J.; Atar, D.; Breithardt, G.; Eikelboom, J.; Ezekowitz, M.D.; Granger, C.B.; Halperin, J.L.; Hohnloser, S.H.; Hylek, E.M.; Kirchhof, P.; Lane, D.A.; Verheugt, F.W.A.; Veltkamp, R.; Lip, G.Y.

2017-01-01

Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic

Conservatively managed pineal apoplexy in an anticoagulated patient

International Nuclear Information System (INIS)

Werder, Gabriel M.; Razdan, Rahul S.; Gagliardi, Joseph A.; Chaddha, Shashi K.B.

2008-01-01

We present a case of pineal apoplexy in an anticoagulated and hypertensive 56-year-old Hispanic male. At presentation, the patient's international normalized ratio (INR) was 10.51 and his blood pressure was 200/130 mmHg. His presenting symptoms included acute onset of headache, chest pain, nausea, vomiting, vertigo, and visual disturbance. Neuroimaging demonstrated hemorrhage into a morphologically normal pineal gland. Under conservative management, the patient experienced gradual resolution of all symptoms excluding the disturbance of upward gaze

Histones Differentially Modulate the Anticoagulant and Profibrinolytic Activities of Heparin, Heparin Derivatives, and Dabigatran.

Science.gov (United States)

Ammollo, Concetta Tiziana; Semeraro, Nicola; Carratù, Maria Rosaria; Colucci, Mario; Semeraro, Fabrizio

2016-02-01

The antithrombin activity of unfractionated heparin (UFH) is offset by extracellular histones, which, along with DNA, represent a novel mediator of thrombosis and a structural component of thrombi. Here, we systematically evaluated the effect of histones, DNA, and histone-DNA complexes on the anticoagulant and profibrinolytic activities of UFH, its derivatives enoxaparin and fondaparinux, and the direct thrombin inhibitor dabigatran. Thrombin generation was assessed by calibrated automated thrombinography, inhibition of factor Xa and thrombin by synthetic substrates, tissue plasminogen activator-mediated clot lysis by turbidimetry, and thrombin-activatable fibrinolysis inhibitor (TAFI) activation by a functional assay. Histones alone delayed coagulation and slightly stimulated fibrinolysis. The anticoagulant activity of UFH and enoxaparin was markedly inhibited by histones, whereas that of fondaparinux was enhanced. Histones neutralized both the anti-Xa and anti-IIa activities of UFH and preferentially blocked the anti-IIa activity of enoxaparin. The anti-Xa activity of fondaparinux was not influenced by histones when analyzed by chromogenic substrates, but was potentiated in a plasma prothrombinase assay. Histones inhibited the profibrinolytic activity of UFH and enoxaparin and enhanced that of fondaparinux by acting on the modulation of TAFI activation by anticoagulants. Histone H1 was mainly responsible for these effects. Histone-DNA complexes, as well as intact neutrophil extracellular traps, impaired the activities of UFH, enoxaparin, and fondaparinux. Dabigatran was not noticeably affected by histones and/or DNA, whatever the assay performed. In conclusion, histones and DNA present in the forming clot may variably influence the antithrombotic activities of anticoagulants, suggesting a potential therapeutic advantage of dabigatran and fondaparinux over heparins. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Application of DBNPA dosage for biofouling control in spiral wound membrane systems

KAUST Repository

Siddiqui, Amber

2017-05-30

Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

Quality of 'Climax' blueberries after low dosage electron beam irradiation

International Nuclear Information System (INIS)

Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

1994-01-01

Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

Economic evaluation of the new oral anticoagulants for the prevention of thromboembolic events: a cost-minimization analysis

Directory of Open Access Journals (Sweden)

Milena Soriano Marcolino

Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Randomized clinical trials have shown that the new oral anticoagulants have at least similar impact regarding reduction of thromboembolic events, compared with warfarin, with similar or improved safety profiles. There is little data on real costs within clinical practice. Our aim here was to perform economic analysis on these strategies from the perspective of Brazilian society and the public healthcare system. DESIGN AND SETTING: Cost-minimization analysis; anticoagulation clinic of Hospital Municipal Odilon Behrens, Belo Horizonte, MG, Brazil. METHODS: Patients at the anticoagulation clinic were recruited between August and October 2011, with minimum follow-up of four weeks. Operational and non-operational costs were calculated and corrected to 2015. RESULTS: This study included 633 patients (59% women of median age 62 years (interquartile range 49-73. The mean length of follow-up was 64 ± 28 days. The average cost per patient per month was $ 54.26 (US dollars. Direct costs accounted for 32.5% of the total cost. Of these, 69.5% were related to healthcare professionals. With regards to indirect costs, 52.4% were related to absence from work and 47.6% to transportation. Apixaban, dabigatran and rivaroxaban were being sold to Brazilian public institutions, on average, for $ 49.87, $ 51.40 and $ 52.16 per patient per month, respectively, which was lower than the costs relating to warfarin treatment. CONCLUSION: In the Brazilian context, from the perspective of society and the public healthcare system, the cumulative costs per patient using warfarin with follow-up in anticoagulation clinics is currently higher than the strategy of prescribing the new oral anticoagulants.

Traumatic events involving elderly patients treated with anticoagulants for atrial fibrillation: the downside of stroke prevention

Directory of Open Access Journals (Sweden)

Alessandro Riccardi

2016-08-01

Full Text Available A group of oral anticoagulant-treated patients affected by permanent atrial fibrillation was evaluated after their access to the emergency room as a result of a traumatic accident. In these patients, the re-evaluation of their risk of thromboembolism and bleeding was performed together with the evaluation of their risk of falling and institutionalization. Results show that the emergency department identifies a cohort of very elderly frail patients, who should be carefully reconsidered for anticoagulant therapy after a traumatic event.

Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome

NARCIS (Netherlands)

Kaandorp, Stef; Di Nisio, Marcello; Goddijn, Mariette; Middeldorp, Saskia

2009-01-01

Background Since hypercoagulability might result in recurrent miscarriage, anticoagulant agents could potentially increase the live-birth rate in subsequent pregnancies in women with either inherited thrombophilia or unexplained recurrent miscarriage. Objectives To evaluate the efficacy and safety

Effectiveness of a Clinical Skills Workshop for drug-dosage calculation in a nursing program.

Science.gov (United States)

Grugnetti, Anna Maria; Bagnasco, Annamaria; Rosa, Francesca; Sasso, Loredana

2014-04-01

Mathematical and calculation skills are widely acknowledged as being key nursing competences if patients are to receive care that is both effective and safe. Indeed, weaknesses in mathematical competence may lead to the administration of miscalculated drug doses, which in turn may harm or endanger patients' lives. However, little attention has been given to identifying appropriate teaching and learning strategies that will effectively facilitate the development of these skills in nurses. One such approach may be simulation. To evaluate the effectiveness of a Clinical Skills Workshop on drug administration that focused on improving the drug-dosage calculation skills of second-year nursing students, with a view to promoting safety in drugs administration. A descriptive pre-post test design. Educational. Simulation center. The sample population included 77 nursing students from a Northern Italian University who attended a 30-hour Clinical Skills Workshop over a period of two weeks. The workshop covered integrated teaching strategies and innovative drug-calculation methodologies which have been described to improve psychomotor skills and build cognitive abilities through a greater understanding of mathematics linked to clinical practice. Study results showed a significant improvement between the pre- and the post-test phases, after the intervention. Pre-test scores ranged between 0 and 25 out of a maximum of 30 points, with a mean score of 15.96 (SD 4.85), and a median score of 17. Post-test scores ranged between 15 and 30 out of 30, with a mean score of 25.2 (SD 3.63) and a median score of 26 (pstudy shows that Clinical Skills Workshops may be tailored to include teaching techniques that encourage the development of drug-dosage calculation skills, and that training strategies implemented during a Clinical skills Workshop can enhance students' comprehension of mathematical calculations. Copyright © 2013 Elsevier Ltd. All rights reserved.

New oral anticoagulant and antiplatelet agents for neurosurgeons.

Science.gov (United States)

Kimpton, George; Dabbous, Bassam; Leach, Paul

2015-01-01

Until recently, warfarin, clopidogrel and aspirin have provided the mainstay for prevention of thrombotic disease in cardiac patients. However, new classes of drugs have recently emerged that promise better clinical outcomes and lower risks. Use of such agents has increased, but increased risk and severity of intra-cranial haemorrhage (ICH) still remain. These cases of intra-cranial bleeds present as emergencies to neurosurgical units. It is of paramount importance that neurosurgical practitioners are aware of those new drugs, useful monitoring tests and available emergency reversal options in case the patient needs emergency intervention. In this review we survey newly available agents in the U.K. at the time of publication. We look at the data provided by the manufacturers, related publications and international guidelines for their use and reversal. New anticoagulants offer a lower incidence of ICH compared with warfarin. Advanced and accurate monitoring tests are emerging, as are prospective data on reversal of anticoagulation in bleeding. Some standard coagulation tests may be of use, whilst reversal agents are available and being evaluated. The trial data shows that new antiplatelet agents have similar or increased incidence and severity of intra-cranial ICH compared with clopidogrel. There is currently limited data on monitoring or reversal. We suggest they may be managed similarly to clopidogrel by using platelet reactivity assays, optimising platelet count and using platelet transfusion with adjunctive agents.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

Science.gov (United States)

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered

Preventive Strategies against Bleeding due to Nonvitamin K Antagonist Oral Anticoagulants

Directory of Open Access Journals (Sweden)

Lessire Sarah

2014-01-01

Full Text Available Dabigatran etexilate (DE, rivaroxaban, and apixaban are nonvitamin K antagonist oral anticoagulants (NOACs that have been compared in clinical trials with existing anticoagulants (warfarin and enoxaparin in several indications for the prevention and treatment of thrombotic events. All NOACs presented bleeding events despite a careful selection and control of patients. Compared with warfarin, NOACs had a decreased risk of intracranial hemorrhage, and apixaban and DE (110 mg BID had a decreased risk of major bleeding from any site. Rivaroxaban and DE showed an increased risk of major gastrointestinal bleeding compared with warfarin. Developing strategies to minimize the risk of bleeding is essential, as major bleedings are reported in clinical practice and specific antidotes are currently not available. In this paper, the following preventive approaches are reviewed: improvement of appropriate prescription, identification of modifiable bleeding risk factors, tailoring NOAC’s dose, dealing with a missed dose as well as adhesion to switching, bridging and anesthetic procedures.

Self-management of oral anticoagulant therapy for mechanical heart valve patients

DEFF Research Database (Denmark)

Christensen, Thomas D; Attermann, Jørn; Pilegaard, Hans K

2001-01-01

.4%–2.9%) for the control group. Conclusion: Self-management of OAT is a feasible and safe concept for selected patients with mechanical heart valve prostheses also on a long-term basis. It provides at least as good and most likely better quality of anticoagulant therapy than conventional management assessed by time within......Objective: Self-management of oral anticoagulant therapy (OAT) has shown good results on a short-term basis. We hypothesize that self-management of OAT provides a better quality of treatment than conventional management also on a long-term basis. The aim of this study was to assess the quality...... of conventionally managed heart valve patients (control group) was used as reference. Results: The median observation time was 1175 days (range: 174–1428 days). The self-managed patients were within therapeutic INR target range for a mean of 78.0% (range: 36.1%–93.9%) of the time compared with 61.0% (range 37...

Guideline-related barriers to optimal prescription of oral anticoagulants in primary care

NARCIS (Netherlands)

Beukenhorst, A. L.; Arts, D. L.; Lucassen, W.; Jager, K. J.; van der Veer, S. N.

2016-01-01

Guidelines provide recommendations for antithrombotic treatment to prevent stroke in people with atrial fibrillation, but oral anticoagulant prescriptions in Dutch primary care are often discordant with these recommendations. Suboptimal guideline features (i.e. format and content) have been

Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants.

Science.gov (United States)

Lanas, Ángel; Carrera-Lasfuentes, Patricia; Arguedas, Yolanda; García, Santiago; Bujanda, Luis; Calvet, Xavier; Ponce, Julio; Perez-Aísa, Ángeles; Castro, Manuel; Muñoz, Maria; Sostres, Carlos; García-Rodríguez, Luis A

2015-05-01

Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants. We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis. Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9-6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4-3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6-2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0-3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0-1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding. Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Haemorrhage in the labyrinth caused by anticoagulant therapy: case report

Energy Technology Data Exchange (ETDEWEB)

Callonnec, F; Gerardin, E; Thiebot, J [Department of Radiology, Rouen University Hospital, 1 rue de Germont, F-76031 Rouen cedex (France); Marie, J P; Andrieu Guitrancourt, J [Department of Otolaryngology, Rouen University Hospital (France); Marsot-Dupuch, K [Department of Radiology, St. Antoine, Paris University Hospital (France)

1999-06-01

We report a patient who experienced a severe vertiginous episode with bilateral tinnitus and progressive right-sided hearing loss. She had Marfan`s disease and was on anticoagulant treatment. The fluid in the labyrinth gave higher signal than cerebrospinal fluid on T1-weighted images, suggesting haemorrhage. The radiological follow-up is discussed. (orig.) With 2 figs., 11 refs.

Impact of CHA2DS2VASc Score on Candidacy for Anticoagulation in Patients With Atrial Fibrillation: A Multi-payer Analysis.

Science.gov (United States)

Patel, Aarti A; Nelson, Winnie W; Schein, Jeff

2016-10-01

The purpose of this study is to report on the effect of using CHA 2 DS 2 VASc (congestive heart failure, hypertension, age ≥75 years [doubled], type 1 or type 2 diabetes mellitus, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) rather than CHADS 2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke) to determine candidacy for anticoagulant prophylaxis in insured patients with atrial fibrillation (AF). Six administrative claims databases that included medical and pharmacy claims for patients aged ≥18 years with a new or existing diagnosis of AF and patient outcomes assessed for 1 year after diagnosis were analyzed. Retrospective health plan data analyses were performed using a software tool (Anticoagulant Quality Improvement Analyzer). Study measures included stroke risk (identified by CHADS 2 and CHA 2 DS 2 VASc scores), bleeding risk (identified by the Anticoagulation and Risk Factors in Atrial Fibrillation score), and anticoagulant use. A total of 115,906 patients with AF (range of mean ages among the 6 databases, 56-79 years) met the inclusion criteria. All ranges reported represent the minimum and maximum values among the 6 databases. Using the CHA 2 DS 2 VASc compared with the CHADS 2 index to assess stroke risk resulted in a 23% to 32% increase in patients considered potential candidates for anticoagulant prophylaxis. This translated to a 38% to 114% increase in the number of ostensibly undertreated patients. Among patients with high stroke and low bleeding risk, 18% to 28% more patients were considered potential candidates for anticoagulation treatment using CHA 2 DS 2 VASc compared with CHADS 2 , or a 57% to 151% increase in the number of undertreated patients. Use of the CHA 2 DS 2 VASc score to determine the risk of stroke increased the number of AF patients for

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

Science.gov (United States)

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality

Conservatively managed pineal apoplexy in an anticoagulated patient

Energy Technology Data Exchange (ETDEWEB)

Werder, Gabriel M. [William Beaumont Hospital, Department of Radiology, 3600 West Thirteen Mile Road, Royal Oak, MI 48073 (United States); St Christopher Iba Mar Diop College of Medicine, Luton (United Kingdom)], E-mail: gabriel_werder@yahoo.com; Razdan, Rahul S.; Gagliardi, Joseph A.; Chaddha, Shashi K.B. [St Vincent' s Medical Center, Bridgeport, CT (United States)

2008-02-15

We present a case of pineal apoplexy in an anticoagulated and hypertensive 56-year-old Hispanic male. At presentation, the patient's international normalized ratio (INR) was 10.51 and his blood pressure was 200/130 mmHg. His presenting symptoms included acute onset of headache, chest pain, nausea, vomiting, vertigo, and visual disturbance. Neuroimaging demonstrated hemorrhage into a morphologically normal pineal gland. Under conservative management, the patient experienced gradual resolution of all symptoms excluding the disturbance of upward gaze.

Recent developments in the use of oral anticoagulants

DEFF Research Database (Denmark)

Lassen, Michael R

2009-01-01

, such as their subcutaneous route of administration or the need for coagulation monitoring. Research was challenged to develop new drugs that would simplify thromboprophylaxis while showing equivalent or better efficacy. Rivaroxaban and dabigatran are now available in some countries for the prevention of venous......For many years, vitamin K antagonists, unfractionated heparins, low-molecular-weight heparins and a pentasaccharide were the only anticoagulant drugs available for the prevention of venous thromboembolism after surgery. However, their benefits were associated with disadvantages...

Anticoagulant therapy for venous thromboembolism detected by Doppler ultrasound in patients with metastatic colorectal cancer receiving bevacizumab

Directory of Open Access Journals (Sweden)

Suenaga M

2015-01-01

Full Text Available Mitsukuni Suenaga, Nobuyuki Mizunuma, Eiji Shinozaki, Satoshi Matsusaka, Masato Ozaka, Mariko Ogura, Keisho Chin, Toshiharu Yamaguchi Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan Background: Doppler ultrasound imaging is useful for management of venous thromboembolism associated with a subclavicular implantable central venous access system in patients receiving bevacizumab (Bev. We investigated the efficacy and safety of our anticoagulant regimen based on Doppler findings.Methods: Patients aged ≤75 years with metastatic colorectal cancer, no history of thromboembolism, and no prior use of Bev received chemotherapy plus Bev. Doppler ultrasound imaging of the deep venous system to detect thrombosis was performed after the first course of Bev and repeated after the third course in patients with asymptomatic thrombosis. Indications for anticoagulant therapy in patients with asymptomatic thrombosis were as follows: enlarging thrombus (E, thrombus >40 mm in diameter (S, thrombus involving the superior vena cava (C, and decreased blood flow (V.Results: Among 79 patients enrolled in this study, asymptomatic thrombosis was detected in 56 patients (70.9% by Doppler ultrasound imaging after the first course of Bev and there was no thrombus in 23 patients (29.1%. Of these 56 patients, 11 (19.6% received anticoagulant therapy with warfarin, including eight after the first course and three after follow-up imaging. S + V was observed in four of 11 patients (36.4%, as well as V in two (18.2%, S + V + C in one (9.1%, E + S + V in one (9.1%, E + C in one (9.1%, E in one (9.1%, and C in one (9.1%. All patients resumed chemotherapy, including seven who resumed Bev. Improvement or stabilization of thrombi was achieved in ten patients (90.9%. Only one patient had symptomatic thromboembolism. Mild bleeding due to anticoagulant therapy occurred in six patients (54.5%, but there were no treatment

Highlights from the Ninth International Symposium of Thrombosis and Anticoagulation (ISTA IX), October 15, 2016, Salvador, Bahia, Brazil.

Science.gov (United States)

Lopes, Renato D; Guimarães, Patricia O; Hylek, Elaine; Feitosa-Filho, Gilson S; Ritt, Luiz; Filgueiras, Nivaldo; Darzé, Eduardo; Rocha, Mario S; Magalhães, Luis P; Sousa, Antonio Carlos Sobral; Correia, Luis Claudio; Oliveira, Lucas Hollanda; Garcia, David A

2017-11-01

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Ninth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, on October 15, 2016. This scientific program was developed by clinicians for clinicians and was promoted by two major clinical research institutes-the Brazilian Clinical Research Institute and the Duke Clinical Research Institute of the Duke University School of Medicine. Comprising academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Intensive Versus Distributed Aphasia Therapy: A Nonrandomized, Parallel-Group, Dosage-Controlled Study.

Science.gov (United States)

Dignam, Jade; Copland, David; McKinnon, Eril; Burfein, Penni; O'Brien, Kate; Farrell, Anna; Rodriguez, Amy D

2015-08-01

Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia. Thirty-four adults with chronic, poststroke aphasia were recruited to participate in an intensive (n=16; 16 hours per week; 3 weeks) versus distributed (n=18; 6 hours per week; 8 weeks) therapy program. Treatment included 48 hours of impairment, functional, computer, and group-based aphasia therapy. Distributed therapy resulted in significantly greater improvements on the Boston Naming Test when compared with intensive therapy immediately post therapy (P=0.04) and at 1-month follow-up (P=0.002). We found comparable gains on measures of participants' communicative effectiveness, communication confidence, and communication-related quality of life for the intensive and distributed treatment conditions at post-therapy and 1-month follow-up. Aphasia Language Impairment and Functioning Therapy resulted in superior clinical outcomes on measures of language impairment when delivered in a distributed versus intensive schedule. The therapy progam had a positive effect on participants' functional communication and communication-related quality of life, regardless of treatment intensity. These findings contribute to our understanding of the effect of treatment intensity in aphasia rehabilitation and have important clinical implications for service delivery models. © 2015 American Heart Association, Inc.

Limited evidence on persistence with anticoagulants, and its effect on the risk of recurrence of venous thromboembolism: a systematic review of observational studies

Directory of Open Access Journals (Sweden)

Vora P

2016-08-01

Full Text Available Pareen Vora, Montse Soriano-Gabarró, Kiliana Suzart, Gunnar Persson Brobert Department of Epidemiology, Bayer Pharma AG, Berlin, Germany Purpose: The risk of venous thromboembolism (VTE recurrence is high following an initial VTE event, and it persists over time. This recurrence risk decreases rapidly after starting with anticoagulation treatment and reduces by ~80%–90% with prolonged anticoagulation. Nonpersistence with anticoagulants could lead to increased risk of VTE recurrence. This systematic review aimed to estimate persistence at 3, 6, and 12 months with anticoagulants in patients with VTE, and to evaluate the risk of VTE recurrence in nonpersistent patients.Methods: PubMed and Embase® were searched up to May 3, 2014 and the search results updated to May 31, 2015. Studies involving patients with VTE aged ≥18 years, treatment with anticoagulants intended for at least 3 months or more, and reporting data for persistence were included. Proportions were transformed using Freeman–Tukey double arcsine transformation and pooled using the DerSimonian–Laird random-effects approach.Results: In total, 12 observational studies (7/12 conference abstracts were included in the review. All 12 studies either reported or provided data for persistence. The total number of patients meta-analyzed to estimate persistence at 3, 6, and 12 months was 71,969 patients, 58,940 patients, and 68,235 patients, respectively. The estimated persistence for 3, 6, and 12 months of therapy was 83% (95% confidence interval [CI], 78–87; I2=99.3%, 62% (95% CI, 58–66; I2=98.1%, and 31% (95% CI, 22–40; I2=99.8%, respectively. Only two studies reported the risk of VTE recurrence based on nonpersistence – one at 3 months and the other at 12 months.Conclusion: Limited evidence showed that persistence was suboptimal with an estimated 17% patients being nonpersistent with anticoagulants in the crucial first 3 months. Persistence declined over 6 and 12 months

Dosage compensation and demasculinization of X chromosomes in Drosophila.

Science.gov (United States)

Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

2010-08-24

The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use.

Science.gov (United States)

Martinelli, Ida; Lensing, Anthonie W A; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A; Cohen, Alexander T; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S; Prins, Martin H

2016-03-17

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an "unacceptable health risk" during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. © 2016 by The American Society of Hematology.

The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

Science.gov (United States)

Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

2013-10-02

Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

Institute of Scientific and Technical Information of China (English)

Somsri Wiwanitkit; Viroj Wiwanitkit

2017-01-01

Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

Dosage of boron traces in graphite, uranium and beryllium oxide

International Nuclear Information System (INIS)

Coursier, J.; Hure, J.; Platzer, R.

1955-01-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

Science.gov (United States)

Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

2018-01-01

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

Directory of Open Access Journals (Sweden)

Qiyuan He

2014-09-01

Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

Current guidelines and prospects for using novel oral anticoagulants for nonvalvular atrial fibrillation

Directory of Open Access Journals (Sweden)

A. V. Fonyakin

2014-01-01

Full Text Available The capabilities of antithrombotic therapy to prevent systemic thromboembolic events in nonvalvular atrial fibrillation (AF are substantially extended after clinically introducing novel oral anticoagulants (NOACs, such as dabigatran, rivaroxaban, and apixaban. World clinical experience with NOACs in AF has confirmed their efficacy and safety in both primary and secondary stroke prevention. At the same time, apixaban additionally reduces the risk of fatal outcomes and it is the safest among the NOACs against hemorrhagic events. The low risks of intracranial hemorrhage typical of NOACs should be taken into account when choosing oral anticoagulant therapy after hemorrhagic stroke in patients athigh risk for thromboembolic events due to AF. Whether NOACs may be used in acute myocardial infarction and during coronary stenting in the presence of nonvalvular AF, left ventricular thromboses, and cardiomyopathies is considered. In real clinical practice, nonvalvular AF may be accompanied by different cardiovascular diseases, by creating the situations where there are no specific guidelines for the use of NOACs. The results of comparing the clinical efficiency of different antithrombotic therapy regimens, the subanalysis of randomized trials, and experts’ opinions may assist a physician to substantiate their decisions. Thus, just a few NOACs that are similar and/or superior to warfarin in efficacy and safety have emerged to date. There are grounds to believe that many physicians will prefer direct anticoagulants to warfarin not only because of their proven efficacy, but also the rapid onset of their anticoagulant effect, neither interaction with a number of foods or drugs, and above all, nor need for regular laboratory blood testing. World post-marketingsurveillance and new clinical tests will be helpful in better estimating the benefits and risks of treatment with NOACs and in expanding indications for their use, which will considerably

Economic evaluation of strategies for restarting anticoagulation therapy after a first event of unprovoked venous thromboembolism.

Science.gov (United States)

Monahan, M; Ensor, J; Moore, D; Fitzmaurice, D; Jowett, S

2017-08-01

Essentials Correct duration of treatment after a first unprovoked venous thromboembolism (VTE) is unknown. We assessed when restarting anticoagulation was worthwhile based on patient risk of recurrent VTE. When the risk over a one-year period is 17.5%, restarting is cost-effective. However, sensitivity analyses indicate large uncertainty in the estimates. Background Following at least 3 months of anticoagulation therapy after a first unprovoked venous thromboembolism (VTE), there is uncertainty about the duration of therapy. Further anticoagulation therapy reduces the risk of having a potentially fatal recurrent VTE but at the expense of a higher risk of bleeding, which can also be fatal. Objective An economic evaluation sought to estimate the long-term cost-effectiveness of using a decision rule for restarting anticoagulation therapy vs. no extension of therapy in patients based on their risk of a further unprovoked VTE. Methods A Markov patient-level simulation model was developed, which adopted a lifetime time horizon with monthly time cycles and was from a UK National Health Service (NHS)/Personal Social Services (PSS) perspective. Results Base-case model results suggest that treating patients with a predicted 1 year VTE risk of 17.5% or higher may be cost-effective if decision makers are willing to pay up to £20 000 per quality adjusted life year (QALY) gained. However, probabilistic sensitivity analysis shows that the model was highly sensitive to overall parameter uncertainty and caution is warranted in selecting the optimal decision rule on cost-effectiveness grounds. Univariate sensitivity analyses indicate variables such as anticoagulation therapy disutility and mortality risks were very influential in driving model results. Conclusion This represents the first economic model to consider the use of a decision rule for restarting therapy for unprovoked VTE patients. Better data are required to predict long-term bleeding risks during therapy in this

Simultaneous Determination of 13 Anticoagulant Rodenticidesin Human Blood by Liquid Chromatography-Tandem Mass Spectrometry and its Application in Three Poisoning Cases.

Science.gov (United States)

Qiao, Zheng; Xiang, Ping; Shen, Baohua; Shen, Min; Yan, Hui

2018-05-01

Anticoagulant rodenticides are widely used for rodent control around the world. A rapid and sensitive method was developed and validated for the simultaneous determination of 13 anticoagulant rodenticides (coumafuryl, pindone, valone, warfarin, coumatetralyl, coumachlor, diphacinone, dicumarol, chlorophacinone, bromadiolone, difenacoum, flocoumafen, and brodifacoum) in human blood by liquid chromatography-tandem mass spectrometry. After liquid-liquid extraction, the anticoagulant rodenticides were separated on an Eclipse Plus C18 column. Linearities were observed for each analyte in blood ranging from 0.5 to 50 ng/mL, with correlation coefficients over 0.99. The limits of detection ranged from 0.01 to 0.2 ng/mL, and the limits of quantification were 0.5 ng/mL for all analytes. The intraday and interday precisions were <15%, and accuracies ranged from 80.3% to 111.0%. This validated method with high sensitivity has been applied in three anticoagulant rodenticide poisoning cases and has been used successfully in monitoring blood concentrations for months. © 2017 American Academy of Forensic Sciences.

A brief history of dosage compensation

Indian Academy of Sciences (India)

depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy

DEFF Research Database (Denmark)

Hansen, Morten Lock; Jepsen, Rikke Malene H G; Olesen, Jonas Bjerring

2015-01-01

-time DC cardioversion for atrial fibrillation between 2000 and 2008. Use of oral anticoagulant therapy within 90 days prior and 360 days after DC cardioversion was obtained from the Danish Register of Medicinal Product Statistics. The risk of thromboembolism was estimated by calculating incidence rates......AIMS: To study the risk of thromboembolism in a nationwide cohort of atrial fibrillation patients undergoing direct current (DC) cardioversion with or without oral anticoagulant coverage. METHODS AND RESULTS: A retrospective study of 16 274 patients in Denmark discharged from hospital after a first...... and by multivariable adjusted Cox proportional-hazard models. During the initial 30 days following discharge, the thromboembolic incidence rate was 10.33 per 100 patient-years for the no prior oral anticoagulant therapy group [n = 5084 (31.2%)], as compared with 4.00 per 100 patient-years for the prior oral...

Self management of oral anticoagulant therapy in children with congenital heart disease

DEFF Research Database (Denmark)

Christensen, Thomas D; Attermann, Jørn; Hjortdal, Vibeke E.

2001-01-01

Objective: The concept of self – management of oral anticoagulation has been shown to entail better quality of treatment than conventional management when assessed in selected adults. We have extended the concept of self – management to include children with congenital cardiac disease......, hypothesizing self-management of oral anticoagulation is also possible in this subset of patients. Our aim was to assess the quality of self-management. Methods: We trained 14 children aged from 2.2 to 15.6 years, with a mean age of 9.7 years, and their parents, in domiciliary analysis of the International...... observed over a mean of 547 days, with a range from 214 to 953 days. The patients were within the therapeutic targetted range of the International Normalized Ratio for a median of 65.5% of the time, with a range from 17.6 % to 90.4 %. None of the patients experienced thromboembolic or bleeding...

Photoselective vaporization of the prostate in men with a history of chronic oral anti-coagulation

Directory of Open Access Journals (Sweden)

Omer F. Karatas

2010-04-01

Full Text Available PURPOSE: A considerable percentage of patients with benign prostatic hyperplasia (BPH also have additional cardiac pathologies, which often require anticoagulant therapy. The aim of this study was to evaluate the efficacy and safety of photoselective vaporization of the prostate (PVP for BPH in cardiac patients receiving anticoagulant therapy. MATERIALS AND METHODS: A total of 67 patients suffering from BPH and high risk cardiac pathologies were operated on using laser prostatectomy. All patients had cardiac pathologies with bleeding disorders requiring anticoagulant use, and underwent standard urologic evaluation for BPH. Patients were treated with laser prostatectomy for relief of the obstruction using the KTP/532 laser energy at 80 W. RESULTS: The mean patient age was 71.4 years (range 55-80. Mean prostate volume on transrectal ultrasonography was 73.2 mL (range 44-120. Operation time ranged from 40 to 90 min, with an average value of 55 min. The average hospital stay was 48 hours (range 12-72 and the Foley catheters were removed within 48 hours, with a mean catheterization time of 34.2 ± 5.9 hours (0-48. No patient required an additional procedure due to severe bleeding necessitating intervention during the early postoperative phase. Mean International symptoms scoring system (IPSS values and post voiding residual volume decreased and peak urinary flow rate increased (p < 0.001. Our results showed that the mean prostate volume had decreased by 53% at 6 months. CONCLUSIONS: High-power photo selective laser vaporization prostatectomy is a feasible, safe, and effective alternative for the minimal invasive management of BPH, particularly in cardiac patients receiving anticoagulant therapy.

Assessment of bleeding during minor oral surgical procedures and extraction in patients on anticoagulant therapy

Directory of Open Access Journals (Sweden)

S Jimson

2015-01-01

Full Text Available Introduction: The risk of postoperative hemorrhage from oral surgical procedures has been a concern in the treatment of patients who are receiving long-term anticoagulation therapy. A study undertaken in our institution to address questions about the amount and severity of bleeding associated with minor outpatient oral surgery procedures by assessing bleeding in patients who did not alter their anticoagulant regimen. Subjects and Methods: Eighty-three patients receiving long-term anticoagulant therapy visited Department of Oral and Maxillofacial Surgery from May 2010 to October 2011 for extractions and minor oral surgical procedures. Each patient was required to undergo preoperative assessment of prothrombin time (PT and measurement of the international normalized ratio. Fifty-six patients with preoperative PT values within the therapeutic range 3-4 were included in the study. The patients′ age ranged between 30 and 75 years. Application of surgispon was done following the procedure. Extraction of teeth performed with minimal trauma to the surrounding tissues, the socket margins sutured, and sutures removed after 5 days. Results: There was no significant incidence of prolonged or excessive hemorrhage and wound infection and the healing process was normal.

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

Science.gov (United States)

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Enoxaparin, effective dosage for intensive care patients: double-blinded, randomised clinical trial

DEFF Research Database (Denmark)

Robinson, Sian; Zincuk, Aleksander; Strøm, Thomas

2010-01-01

ABSTRACT: INTRODUCTION: Intensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine...

Stabilization of the E* Form Turns Thrombin into an Anticoagulant

Energy Technology Data Exchange (ETDEWEB)

Bah, Alaji; Carrell, Christopher J.; Chen, Zhiwei; Gandhi, Prafull S.; Di Cera, Enrico; (WU-MED)

2009-07-31

Previous studies have shown that deletion of nine residues in the autolysis loop of thrombin produces a mutant with an anticoagulant propensity of potential clinical relevance, but the molecular origin of the effect has remained unresolved. The x-ray crystal structure of this mutant solved in the free form at 1.55 {angstrom} resolution reveals an inactive conformation that is practically identical (root mean square deviation of 0.154 {angstrom}) to the recently identified E* form. The side chain of Trp215 collapses into the active site by shifting >10 {angstrom} from its position in the active E form, and the oxyanion hole is disrupted by a flip of the Glu192-Gly193 peptide bond. This finding confirms the existence of the inactive form E* in essentially the same incarnation as first identified in the structure of the thrombin mutant D102N. In addition, it demonstrates that the anticoagulant profile often caused by a mutation of the thrombin scaffold finds its likely molecular origin in the stabilization of the inactive E* form that is selectively shifted to the active E form upon thrombomodulin and protein C binding.

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

Management strategies for optimal control of anticoagulation in patients with atrial fibrillation

NARCIS (Netherlands)

Levi, Marcel; De Peuter, Olaf R.; Kamphuisen, Pieter W.

2009-01-01

Most patients with atrial fibrillation need anticoagulant treatment with vitamin K antagonists for prevention of thromboembolism, in particular ischemic stroke. Many studies show the efficacy of this treatment but also that it is difficult to keep patients who use vitamin K antagonists in the proper

Treatment of patients with a history of heparin-induced thrombocytopenia and anti-lepirudin antibodies with argatroban.

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Harenberg, Job; Job, Harenberg; Jörg, Ingrid; Ingrid, Jörg; Fenyvesi, Tivadar; Tivadar, Fenyvesi; Piazolo, Lukas; Lukas, Piazolo

2005-02-01

Patients with heparin-induced thrombocytopenia (HIT) type II require anticoagulation with non-heparin immediate acting anticoagulants. Danaparoid may cross react with HIT-antibodies and lepirudin may generate anti-lepirudin antibodies influencing anticoagulation. We hypothesised, that the synthetic small molecular thrombin inhibitor argatroban does not induce immunoglobulins reacting towards lepirudin in patients with anti-lepirudin antibodies in the history and that titration of the anticoagulation may be easier with argatroban. We report on the treatment of four patients of a study, which was terminated prematurely due to official warnings for a repeated use of lepirudin. Two patients each received argatroban and lepirudin intravenously. A blinded assessor adjusted the doses of the anticoagulants to 1.5-3.0 fold prolongation of the aPTT. Ecarin clotting time (ECT), concentrations of lepirudin (ELISA) and of argatroban (gas-chromatography with mass spectrometry), and the generation of lepirudin antibodies (ELISA) were measured. APTT-adjusted dosages for argatroban was 2.0-2.6 microg/kg.min and for lepirudin 48-149 microg/kg.h. ECT was prolonged 2.1 to 4.5-fold with lepirudin and 4 to 7-fold with argatroban. The concentration of lepirudin ranged between 750 and 1500 ng/ml and of argatroban between 400 and 1100 ng/ml. Patients on argatroban did not generate immunoglobulin IgG reacting towards lepirudin in contrast to both patients on lepirudin who developed anti-lepirudin antibodies. Both treatments were well tolerated. Despite the low number of patients argatroban seems to lead to a more stable anticoagulant response than lepirudin resulting in a lower variability of the dosage for prophylaxis or treatment of thromboembolism of patients with a history of HIT and lepirudin antibodies.

Comparison of hematologic values in blood samples with lithium heparin or dipotassium ethylenediaminetetraacetic acid anticoagulants in Hispaniolan Amazon parrots (Amazona ventralis).

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Guzman, David Sanchez-Migallon; Mitchell, Mark A; Gaunt, Stephen D; Beaufrère, Hugues; Tully, Thomas N

2008-06-01

Blood samples were collected from 20 Hispaniolan Amazon parrots (Amazona ventralis) and were divided into tubes that contained dipotassium ethylenediaminetetraacetic acid (K2EDTA) and lithium heparin. Complete blood cell counts were determined in each sample within 2 hours of collection. The level of agreement in results was moderate for plasma protein, packed cell volume (PCV), and leukocyte, monocyte, and lymphocyte counts between the anticoagulants. Plasma protein and PCV values were significantly lower in samples with lithium heparin than in those with K2EDTA, whereas lymphocyte numbers were significantly higher in lithium heparin samples than in K2EDTA samples. The level of agreement was good for the other cell types (heterophils, eosinophils, and basophils) when comparing the different anticoagulants. The poor level of agreement between anticoagulants with the increase in thrombocyte clumping in lithium heparin samples indicates that the use of lithium heparin as anticoagulant may affect thrombocyte count. No negative effects on morphology and staining of blood cells were apparent in smears from heparin samples compared with K2EDTA samples. Within the different values compared, the limits of agreement are small enough to be confident that lithium heparin can be used for routine CBC counts in a clinical setting. The use of the same anticoagulant should be recommended to follow trends within the same patient, especially when considering plasma protein concentration, PCV, and lymphocyte count.

Interpreting the quality of health care database studies on the comparative effectiveness of oral anticoagulants in routine care

Directory of Open Access Journals (Sweden)

Schneeweiss S

2013-09-01

Full Text Available Sebastian Schneeweiss, Krista F Huybrechts, Joshua J Gagne Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Background: Dabigatran, an oral direct thrombin inhibitor, has now been available for 2 years in the US for the prevention of stroke in patients with nonvalvular atrial fibrillation, and direct Xa inhibitors are also starting to enter the market. Studies examining the effects of new oral anticoagulants in health care databases are beginning to emerge. The purpose of this study was to describe the validity of early published observational studies on the comparative safety and effectiveness of new oral anticoagulants in patients with atrial fibrillation. Methods: We identified published nonrandomized post-marketing studies (articles or conference abstracts or posters and critically appraised their internal validity, with a particular focus on their ability to control confounding and other biases. Results: Two full-length journal articles, three conference posters, two conference presentation abstracts, and a US Food and Drug Administration analysis form the basis of the early comparative effectiveness and safety experience with new oral anticoagulants. Some published studies exhibit substantial biases and have insufficient precision for several important endpoints. Several studies suffer from biases arising from comparing ongoing users of the older drug, warfarin, who seem to tolerate it, to initiators of the new treatment who may have switched from warfarin or have had no prior experience with anticoagulants. Analyses tended to not adjust or not adjust adequately for confounding, and unsound propensity score application was also observed. Several studies introduced selection bias by excluding patients who died during follow-up and by restricting the study population to those with continuous database enrollment following cohort entry. We

On the exfoliating polymeric cellular dosage forms for immediate drug release.

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Blaesi, Aron H; Saka, Nannaji

2016-06-01

The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

[Non-bacterial thrombotic endocarditis on the bicuspid aortic valve in a 25-year-old male with lupus anticoagulant].

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Elikowski, Waldemar; Jarząbek, Radosław; Małek, Małgorzata; Witczak, Włodzimierz; Łazowski, Stanisław; Psuja, Piotr

2016-03-01

Non-bacterial thrombotic endocarditis (NBTE) is characterized by presence of sterile vegetations that develop from fibrin and platelets on heart valves. The main conditions predisposing to NBTE are malignancy, autoimmune diseases and other hypercoagulable states. The authors describe a case of a 25-year-old male, in whom NBTE was diagnosed on the bicuspid aortic valve. The presence of significant aortic regurgitation and dental caries were initially suggestive of infective endocarditis; although, serial blood culture were negative and procalcytonin concentration was within normal ranges. Empiric antibiotic therapy did not result in diminishing of vegetations, similarly to the anticoagulation treatment initiated when strongly positive lupus anticoagulant was detected in laboratory findings. Aortic valve replacement was necessary. Bacteriologic examination of the excised valve was negative. Widespread fibrin masses at different stages of organization on the leaflets confirmed NBTE in histopathologic assessment. Lupus anticoagulant was probably secondary to thyroid autoimmune disease. © 2016 MEDPRESS.

Anticoagulation Control in Patients With Nonvalvular Atrial Fibrillation Attended at Primary Care Centers in Spain: The PAULA Study.

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Barrios, Vivencio; Escobar, Carlos; Prieto, Luis; Osorio, Genoveva; Polo, José; Lobos, José María; Vargas, Diego; García, Nicolás

2015-09-01

To determine the current status of anticoagulation control in patients with nonvalvular atrial fibrillation treated with vitamin K antagonists in the primary care setting in Spain. The PAULA study was a multicenter cross-sectional/retrospective observational study conducted throughout Spain. The study included patients with nonvalvular atrial fibrillation who had been receiving vitamin K antagonist therapy during the past year and were attended at primary care centers. International normalized ratio (INR) values over the past 12 months were recorded. The degree of anticoagulation control was defined as the time the patient had remained within the therapeutic range and was determined by both the direct method (poor control < 60%) and by the Rosendaal method (poor control < 65%). The study assessed 1524 patients (mean age, 77.4 ± 8.7 years; 48.6% women; 64.2% in permanent atrial fibrillation; CHADS2 mean, 2.3 ± 1.2; CHA2DS2-VASc, 3.9 ± 1.5, and HAS-BLED, 1.6 ± 0.9). The mean number of INR readings recorded per patient was 14.4 ± 3.8. A total of 56.9% of patients had adequate INR control according to the direct method and 60.6% according to the Rosendaal method. The multivariate analysis identified the following predictors for poor INR control: female sex, dietary habits potentially affecting anticoagulation with vitamin K antagonists, multidrug therapy, and a history of labile INR. Approximately 40% of patients (43.1% by the direct method and 39.4% by the Rosendaal method) with nonvalvular atrial fibrillation who were receiving anticoagulation therapy with vitamin K antagonists in primary care in Spain had poor anticoagulation control during the previous 12 months. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use

NARCIS (Netherlands)

Martinelli, Ida; Lensing, Anthonie W. A.; Middeldorp, Saskia; Levi, Marcel; Beyer-Westendorf, Jan; van Bellen, Bonno; Bounameaux, Henri; Brighton, Timothy A.; Cohen, Alexander T.; Trajanovic, Mila; Gebel, Martin; Lam, Phuong; Wells, Philip S.; Prins, Martin H.

2016-01-01

Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation.

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

Monitoring the Effects and Antidotes of the Non-vitamin K Oral Anticoagulants

DEFF Research Database (Denmark)

Rahmat, Nur A; Lip, Gregory Y H

2015-01-01

In the last decade, we have witnessed the emergence of the oral non-vitamin K oral anticoagulants (NOACs), which have numerous advantages compared with the vitamin K antagonists, particularly their lack of need for monitoring; as a result their use is increasing. Nonetheless, the NOACs face two...

Home management of oral anticoagulation via telemedicine versus conventional hospital-based treatment

DEFF Research Database (Denmark)

Christensen, Henry; Lauterlein, Jens-Jacob; Sørensen, Patricia D

2011-01-01

We have developed an expert computer system for the control of oral anticoagulation therapy, accessible by the patients via their own computer. To investigate if the weekly measurement and dosing of international normalized ratio (INR) at home using the online Internet-based system was superior t...

Self-compacting concretes (SCC: comparison of methods of dosage

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B. F. Tutikian

Full Text Available The composition of a self-compacting concrete (SCC should be defined to fulfills a number of requirements, such as self-compactibility, strength and durability. This study aims to compare three methods of dosage for SCC with local materials, so as to determine which one is the most economical and rational, thus assisting the executor in making a decision and enabling economic and technical feasibility for its application. The methods used in the experimental program were: Nan Su et al., which was developed in 2001 [1]; Repette-Melo, which was proposed in 2005 [2]; and Tutikian & Dal Molin, which was developed in 2007 [3]. From the results obtained in the experimental program, it was observed that the method which presented the lowest cost and highest compressive strength at the ages of 7, 28 and 91 days was Tutikian & Dal Molin, while the one which reached the lowest chloride ion penetration, best compactness and highest elasticity modulus was Repette-Melo. In tests carried out in the fresh state, all tested methods yielded mixtures which comply with the self-compactibility levels required by ABNT NBR 15823:2010 [4].

Retroperitoneal Bleeding: An Experience During Prophylactic Anticoagulation in a Patient With Nephrotic Syndrome

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Mari Okada

2017-07-01

Full Text Available The association between nephrotic syndrome (NS and a hypercoagulable state has been demonstrated. Controlling the blood clotting activity may therefore be attractive for patients with nephrosis in terms of thromboembolism prophylaxis. We herein report a 75-year-old woman with minimal change disease who developed pains in the right back, groin, and thigh because of retroperitoneal bleeding during prophylactic anticoagulation with unfractionated heparin. Although this procedure has not been accepted as the standard of care for patients with nephrosis, pharmacologic prophylaxis may already be practiced empirically, as in the present patient. We believe that our experience highlights the pitfalls of such a management in patients with nephrosis, implying the need for a diagnostic strategy for identifying those patients with NS who can benefit from prophylactic anticoagulation. Several concerns that emerged in this case are also discussed.

Anticoagulant, antiplatelet and antianemic effects of Punica granatum (pomegranate) juice in rabbits.

Science.gov (United States)

Riaz, Azra; Khan, Rafeeq A

2016-04-01

Pomegranate (Punica granatum L., Punicaceae) is a good source of minerals and phytochemicals with diverse pharmacological activities such as anxiolytic, antidepressant, hypoglycemic, hypolipidemic, and anti-inflammatory activities. Effects of P. granatum on blood parameters and coagulation have, however, been little studied. The aim of the study was to assess the outcome of P. granatum on coagulation and anticoagulation factors at different doses on blood samples of healthy white rabbits. Blood samples of the animals were collected twice during the study and biochemical assays were performed to assess the effect on hematological, coagulation, anticoagulation, and platelet aggregation. Significant changes were observed in erythrocytes, hemoglobin, and mean corpuscular hemoglobin concentration, while bleeding and thrombin time were also prolonged significantly. There was significant increase in protein C, thrombin antithrombin complex levels, and decrease in platelet aggregation and fibrinogen concentration, in a dose-dependent manner. The results of hematological and coagulation assays lead to the speculation about a possible antianemic and cardioprotective effect of P. granatum.

Anticoagulants for the treatment of recurrent pregnancy loss in women without antiphospholipid syndrome

NARCIS (Netherlands)

Di Nisio, M.; Peters, L. W.; Middeldorp, S.

2005-01-01

BACKGROUND: Since hypercoagulability might result in recurrent pregnancy loss, anticoagulant agents could potentially increase the live-birth rate in subsequent pregnancies in women with either inherited thrombophilia or unexplained pregnancy loss. OBJECTIVES: To evaluate the efficacy and safety of

Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

Science.gov (United States)

Mahan, Charles E

2015-04-01

Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

Anticoagulant effects of inhaled unfractionated heparin in the dog as determined by partial thromboplastin time and factor Xa activity.

Science.gov (United States)

Manion, Jill S; Thomason, John M; Langston, Vernon C; Claude, Andrew K; Brooks, Marjory B; Mackin, Andrew J; Lunsford, Kari V

2016-01-01

To evaluate the anticoagulant effects of inhaled heparin in dogs. This study was conducted in 3 phases. In phase 1, bronchoalveolar lavage fluid (BALf) was collected to generate an in vitro calibration curve to relate heparin concentration to the activated partial thromboplastin time (aPTT). In phase 2, heparin was administered via nebulization to determine the threshold dose needed to prolong systemic aPTT. In phase 3, the local anticoagulant activity of inhaled heparin was determined by measurement of BALf anti-Xa activity and aPTT. University teaching hospital. Six healthy intact female Walker Hounds were used in this study. Two dogs were used for each phase. Inhaled unfractionated sodium heparin was administered in doses ranging from 50,000 to 200,000 IU. In vitro addition of heparin to BALf caused a prolongation in aPTT. Inhaled heparin at doses as high as 200,000 IU failed to prolong systemic aPTT, and a threshold dose could not be determined. No significant local anticoagulant effects were detected. Even at doses higher than those known to be effective in people, inhaled heparin appears to have no detectable local or systemic anticoagulant effects in dogs with the current delivery method. © Veterinary Emergency and Critical Care Society 2015.

Outcome of Secondary Stroke Prevention in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants.

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Nakase, Taizen; Moroi, Junta; Ishikawa, Tatsuya

2018-05-01

Since non-vitamin K antagonist oral anticoagulants (NOACs) were released for clinical use, many studies have investigated its effectiveness in stroke prevention. In this study, to determine whether or not there is a difference in outcome in secondary stroke prevention between warfarin and NOACs, patients with embolic stroke with newly prescribed anticoagulants were prospectively analyzed. Patients with acute ischemic stroke, who newly started anticoagulant therapy, were consecutively asked to participate in this study. Enrolled patients (76.3 ± 11.0 years old) were classified into warfarin (n = 48), dabigatran (n = 73), rivaroxaban (n = 49), and apixaban (n = 65). The outcome in 1 year was prospectively investigated at outpatient clinic or telephone interview. Recurrence of stroke and death was considered as the critical incidence. The prevalence of risk factors was not different among all medicines. Patients with dabigatran showed significantly younger onset age (P incident rates were 7.1%, 15.3%, 19.0%, and 29.7% for dabigatran, apixaban, rivaroxaban, and warfarin, respectively. Dabigatran showed relatively better outcome compared with warfarin (P = .069) and rivaroxaban (P = .055). All patients on NOACs presented lower cumulative stroke recurrence compared with warfarin. Even in the situation of secondary stroke prevention, noninferiority of NOACs to warfarin might be demonstrated. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

Science.gov (United States)

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

Polysaccharides and their depolymerized fragments from Costaria costata: Molecular weight and sulfation-dependent anticoagulant and FGF/FGFR signal activating activities.

Science.gov (United States)

Hou, Ningning; Zhang, Meng; Xu, Yingjie; Sun, Zhongmin; Wang, Jing; Zhang, Lijuan; Zhang, Quanbin

2017-12-01

Crude polysaccharides from Costaria costata were extracted by hot water and further fractionated by anion exchange chromatography into three polysaccharide fractions. Three low molecular weight fragments were then prepared by degradation of the polysaccharides with hydrogen peroxide and ascorbic acid. The structural features of the polysaccharides and their low molecular weight fragments were elucidated for the first time based on the HGPC, FT-IR, NMR, MS, monosaccharide composition, and other chemical analyses. Their anticoagulant and FGF-1, -2, -7, -8, -9, -10/FGFR1c signaling activation activities in BaF3 cells were also examined. Our studies showed that the polysaccharides were sulfated at different positions of galactose and fucose residues. The APTT-, PT- and TT-based anticoagulant assay results indicated that a high molecular weight and a higher degree of sulfation were essential for their anticoagulant activities. In contrast, not only the polysaccharides but also the depolymerized fragments showed significant FGF/FGFR signal activating activities in a FGF-, molecular weight-, and sulfation-dependent manner. The results presented in current study demonstrated the potential use of the polysaccharides and their fragments as anticoagulants and FGF signal regulators. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy

Directory of Open Access Journals (Sweden)

Nagarik Amit

2010-01-01

Full Text Available Systemic heparinization during continuous renal replacement therapy (CRRT is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT > 55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 pa-tients including 42 males. Co-morbidities were comparable in both groups. HMARF was signifi-cantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 ± 6.4 hours while it was 24.5 ± 6.36 hours in heparin free group ( P=NS. Patients receiving heparin had 16 bleeding episodes (0.45/patient while only four bleeding episodes occurred in heparin free group (0.13/patient, P< 0.05. Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.

Managing hip fracture and lower limb surgery in the emergency setting: Potential role of non-vitamin K antagonist oral anticoagulants.

Science.gov (United States)

Fisher, William

2017-06-01

Trauma, immobilization, and subsequent surgery of the hip and lower limb are associated with a high risk of developing venous thrombo-embolism (VTE). Individuals undergoing hip fracture surgery (HFS) have the highest rates of VTE among orthopedic surgery and trauma patients. The risk of VTE depends on the type and location of the lower limb injury. Current international guidelines recommend routine pharmacological thromboprophylaxis based on treatment with heparins, fondaparinux, dose-adjusted vitamin K antagonists and acetylsalicylic acid for patients undergoing emergency HFS; however, not all guidelines recommend pharmacological prophylaxis for patients with lower limb injuries. Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for VTE prevention after elective hip or knee replacement surgery, but at present are not widely recommended for other orthopedic indications despite their advantages over conventional anticoagulants and promising real-world evidence. In patients undergoing HFS or lower limb surgery, decisions on whether to anticoagulate and the most appropriate anti-coagulation strategy can be guided by weighing the risk of thromboprophylaxis against the benefit in relation to each patient's medical history and age. In addition, the nature and location of the fracture, operating times and times before fracture fixation should be considered. The current review discusses the need for anticoagulation in patients undergoing emergency HFS or lower limb surgery together with the current guidelines and available evidence on the use of NOACs in this setting. Appropriate thromboprophylactic strategies and practical advice on the peri-operative management of patients who present to the Emergency Department on a NOAC before emergency surgery are further outlined.

Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

Science.gov (United States)

Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

2018-01-01

Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

Short-time, high-dosage penicillin infusion therapy of syphilis

DEFF Research Database (Denmark)

Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

2003-01-01

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

The presence of mathematics and computer anxiety in nursing students and their effects on medication dosage calculations.

Science.gov (United States)

Glaister, Karen

2007-05-01

To determine if the presence of mathematical and computer anxiety in nursing students affects learning of dosage calculations. The quasi-experimental study compared learning outcomes at differing levels of mathematical and computer anxiety when integrative and computer based learning approaches were used. Participants involved a cohort of second year nursing students (n=97). Mathematical anxiety exists in 20% (n=19) of the student nurse population, and 14% (n=13) experienced mathematical testing anxiety. Those students more anxious about mathematics and the testing of mathematics benefited from integrative learning to develop conditional knowledge (F(4,66)=2.52 at pComputer anxiety was present in 12% (n=11) of participants, with those reporting medium and high levels of computer anxiety performing less well than those with low levels (F(1,81)=3.98 at pmathematical and computer anxiety when planning an educational program to develop competency in dosage calculations.

Effects of citrate-enriched bicarbonate based dialysate on anticoagulation and dialyzer reuse in maintenance hemodialysis patients.

Science.gov (United States)

Rocha, Amanda D; Padua, Vanessa C; Oliveira, Esther; Guimaraes, Márcia M; Lugon, Jocemir R; Strogoff de Matos, Jorge P

2014-04-01

Systemic anticoagulation with unfractionated heparin is commonly used in maintenance hemodialysis (HD), but it increases the risk of bleeding complications. We investigated whether the use of citrate-enriched bicarbonate based dialysate (CD) would reduce systemic anticoagulation without compromising the efficacy of reprocessed dialyzers. This is a crossover study in which half of a total of 30 patients initially underwent HD with acetate-enriched bicarbonate based dialysate and a standard heparin dose of ∼ 100 IU/kg (Treatment A), whereas the remaining patients were treated with CD and a 30% reduced heparin dose (Treatment B). After 12 consecutive HD sessions in each treatment, the dialysate and heparin doses were reversed, then followed for another period of 12 HD sessions. The two treatment phases were split by a washout period of six HD sessions using acetate-enriched bicarbonate based dialysate and standard heparin dose. Systemic anticoagulation was higher in Treatment A. The activated partial thromboplastin time at the end of HD session was 68 ± 36 seconds in Treatment A and 47 ± 16 seconds in Treatment B (P = 0.005). Sixty-eight percent of the dialyzers remained adequate until the 12th use in Treatment A and 61% did so in Treatment B (P = 0.63). Patients had three and 24 cramps episodes during Treatment A and B, respectively (P < 0.001). Nine and 26 symptomatic intradialytic hypotension episodes were seen in Treatment A and B, respectively, (P = 0.003). In conclusion, the use of CD had a favorable effect on anticoagulation in the extracorporeal circuit in patients on maintenance HD, but it was also associated with more hypotension and cramps. © 2013 International Society for Hemodialysis.

Cost of vitamin K antagonist anticoagulant treatment in patients with metallic prosthetic valve in mitral position.

Science.gov (United States)

Ene, Gabriela; Garcia Raso, Aránzazu; Gonzalez-Dominguez Weber, Almudena; Hidalgo-Vega, Álvaro; Llamas, Pilar

2016-01-01

The initiation of oral anticoagulation therapy after valve replacement surgery requires strict monitoring because these patients are at high risk for the development of thrombotic complications and present an increased risk of bleeding. The aim of this study was to examine the total healthcare costs of oral anticoagulant treatment with vitamin K antagonists in patients with metallic prosthetic valves in the mitral position. Data from clinical records were used in the study including international normalized ratio results, number of medical visits, type of anticoagulant, use of rescue medication and hospital admissions from related complications. The drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included in the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the diagnosis-related group price for each case. We collected data from 151 patients receiving oral anticoagulation therapy with vitamin K antagonist who were diagnosed with mitral prosthesis (n = 90), mitro-aortic prosthesis (n = 57), and mitral and tricuspid prosthesis (n = 4). The total direct healthcare cost was €15302.59, with a mean total cost per patient per year of €1558.15 (±2774.58) consisting of 44.38 (±42.30) for drug cost, €71.41 (±21.43) for international normalized ratio monitoring, €429.52 (±126.87) for medical visits, €26.31 (±28.38) for rescue medication and €986.53 (±2735.68) for related complications. Most direct healthcare costs associated with the sampled patients arose from the specialist-care monitoring required for treatment. Good monitoring is inversely related to direct healthcare costs.

Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?

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Shim, Choong Nam; Chung, Hyun Soo; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Kim, Ha Yan; Kim, Dong Wook; Lee, Hyuk

2016-01-01

The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.

Assessment of anticoagulation treatments in non-valvular atrial fibrillation patients diagnosed in a basic health area.

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Aguilera Alcaraz, Beatriz M; Abellán Huerta, José; Carbayo Herencia, Julio Antonio; Ariza Copado, Consuelo; Hernández Menárguez, Fernando; Abellán Alemán, José

Atrial fibrillation (AF) is the most common cardiac arrhythmia. To assess the need for anticoagulation is essential for its management. Our objective was to investigate whether the indication of anticoagulation was adequate in patients diagnosed with non-valvular AF, given the CHA2-DS2-VASc scale, measuring the International Normalizad Ratio range (INR) in patients treated with anti-vitamin K drugs. This is an observational and cross sectional study. 232 patients with atrial fibrillation were included. We analyzed demographic, the CHA2-DS2-VASc and HAS-BLED variables, the treatment and INR values for 6 consequentive months. The confrontation of variables was performed using chi-square and Mantel-Haenzel test. The prevalence of AF was 1.05%. The 88.4% had CHA2-DS2-VASc ≥ 2. The 71.1% were taking anticoagulants, of which 58.2% were under antivitamin k. The 46.7% of patients taking antivitamin K, presented inadequate range of INR. There was a greater prescription of antivitamin k in patients with persistent or permanent AF compared to the paroxysmal form (62.8 vs. 37.2% p<.001). The use of drugs that increase bleeding was associated with a worse control of INR after adjustment for the main variables of clinical relevance (odds ratio 2.17 [1.02-4.59], p=.043). The level of anticoagulation with antivitamin K was inadequate in our sample, despite a proper follow up and adherence to treatment. Patients with paroxysmal AF received less antivitamin K than those with persistent/permanent AF. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.

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Boroumand, Mohammadali; Goodarzynejad, Hamidreza

2010-01-01

Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio (INR) was introduced to "normalize" all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation

Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?

Science.gov (United States)

Lucke-Wold, Brandon P; Turner, Ryan C; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay

2016-01-01

Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion

Changes in oral anticoagulation for elective cardioversion: results from a European cardioversion registry.

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Papp, Judit; Zima, Endre; Bover, Ramon; Karaliute, Rasa; Rossi, Andrea; Szymanski, Catherine; Troccoli, Rossella; Schneider, Jonas; Fagerland, Morten Wang; Camm, A John; Atar, Dan

2017-07-01

In patients with atrial fibrillation (AF) pharmacological or electrical cardioversion may be performed to restore sinus rhythm. The procedure is associated with an increased risk of thromboembolic events, which can be significantly reduced by adequate anticoagulation (OAC). Our aim was to create a partly prospective, partly retrospective cardioversion registry, particularly focusing on OAC strategies in different European countries, and on emerging choice of OAC over time. From September 2014 to October 2015, cardioversions due to AF performed in six European city hospitals in five European countries (Hungary: Budapest-1 and -2; Italy: Bari and Pisa; France: Amiens; Spain: Madrid; and Lithuania: Kaunas) were recorded in the registry. A total of 1101 patients (retrospective/prospective: 679/422, male/female: 742/359, mean age: 67.3 years ± 11.2) were registered. Most of the cardioversions were electrical (97%). Oral anticoagulants were administered in 87% of the patient, the usage of non-VKA oral anticoagulants (NOACs) vs Vitamin K antagonists (VKA) was 31.5% vs 68.5%, respectively. Seventy seven percent of the patients were given oral anticoagulants more than 3 weeks prior to the procedure, and 86% more than 4 weeks after the procedure. When using VKA, international normalized ratio (INR) at cardioversion was above 2.0 in 76% of the cases. A decline in VKA usage (P = 0.033) in elective cardioversion over approximately 1 year was observed. During the observation period, there was an increase in apixaban (P < 0.001), a slight increase in rivaroxaban (P = 0.028) and no changes in dabigatran (P = 0.34) usage for elective cardioversion. There were differences in use of OAC between the countries: Spain used most VKA (89%), while France used least VKA (39%, P < 0.001). According to current AF guidelines, NOACs are adequate alternatives to VKA for thromboembolic prevention in AF patients undergoing elective cardioversion. Our results indicate that

UPLC-ESI-QTOF/MS and multivariate data analysis for blood plasma and serum metabolomics: effect of experimental artefacts and anticoagulant

DEFF Research Database (Denmark)

Barri, Thaer; Dragsted, Lars Ove

2013-01-01

agents, e.g. heparin, EDTA and citrate. In the present study, we looked into metabolite and other differences in matched serum and plasma samples and different plasma preparations by using untargeted UPLC-ESI-QTOF/MS profiling and multivariate data analysis (PCA and OPLS-DA). Metabolite differences......Clotting and anticoagulation of blood samples may give rise to different metabolic profiles of serum and plasma samples, respectively. The anticoagulant used for blood plasma preparation may affect the resulting metabolic profile due to different mechanisms involved in anticoagulation by various...... between serum and plasma samples were mainly related to small peptides reflecting presence or absence of coagulation. Only subtle metabolite differences between the different plasma preparations were noticed, which were primarily related to ion suppression or enhancement caused by citrate and EDTA...

Genetic basis for dosage sensitivity in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Isabelle M Henry

2007-04-01

Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

Recurrent deep venous thrombosis during optimal anticoagulation and overt hyperthyroidism: a case report

NARCIS (Netherlands)

Squizzato, Alessandro; Vitale, Josè; Gerdes, Victor Ea; Romualdi, Erica; Büller, Harry R.; Ageno, Walter

2007-01-01

Recurrent deep venous thrombosis despite well conducted anticoagulant treatment is an uncommon, but possible, event. It has been hypothesized that overt hyperthyroidism may increase thromboembolic risk. We present the case of an elderly man with a recurrent episode of deep venous thrombosis during

New oral anticoagulants: key messages for clinicians

Directory of Open Access Journals (Sweden)

Matteo Giorgi-Pierfranceschi

2013-12-01

Full Text Available New oral anticoagulants are an effective and safe alternative to vitamin K antagonists in many fields of clinical practice. The use of the direct inhibitors of activated Factor II (dabigatran and activated Factor X (apixaban and rivaroxaban, both in patients with non-valvular atrial fibrillation (NVAF and those with acute venous thromboembolism (VTE, is of great interest for internal medicine physicians. This paper aims to give practical guidance on management (starting therapy, follow up and bleeding complications of patients treated with dabigatran, rivaroxaban or apixaban for NVAF or acute VTE providing practical tables concerning the phases of therapy, management of complications, drug interaction and dose adjustment if renal impairment occurs.

Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

Directory of Open Access Journals (Sweden)

W. Frank Peacock

2016-01-01

Full Text Available Nonvalvular atrial fibrillation- (NVAF- related stroke and venous thromboembolism (VTE are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.

Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

International Nuclear Information System (INIS)

Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

2002-01-01

Background and Aim: Adult patients are generally, irrespective of size, given the same amount of activity for a certain type of nuclear medicine examination, a standard dosage. Identical image quality is essential when comparing different patient studies. The aim of this study is to evaluate different dosage methods for Tc-99m-MDP bone scintigraphy and to investigate whether individual dosage will decrease the variations in image quality between different patients. Material and Methods: 100 consecutive adult patients (aged between 40 and 89 years) undergoing whole body bone scintigraphy were studied. Eight patients were excluded from the study because of abnormal high uptake in the areas of interest. The patient weight and height were registered. The activity in the syringes was measured before and after the injection of about 600 MBq Tc-99m MDP. Scanning was performed, with a dual head gamma camera (Maxxus or Millennium VG, General Electric) equipped with a high-resolution collimator, at approximately 4 hours (mean 3.8 h) post-injection. Regions of interest (ROI) were drawn over the lumbar spine (posterior view), the right femur (anterior view) and also soft tissue background regions for each area. The total counts, maximum counts/pixel and number of pixels in the ROIs were registered. The maximum number of counts/pixel (background-subtracted), SPINEmax and FEMURmax were chosen as the image quality parameters. For each patient, SPINEmax and FEMURmax where recalculated to the number that would have been obtained with standard dosage (exactly 600 MBq), and dosage proportional to body weight, body surface area and body height. All values were corrected to a scanning time 3.8 h after injection. Results: Both with a standard activity dosage and a dosage proportional to body height, SPINEmax decreases with increasing body weight. Dosage proportional to body weight gives increasing values of SPINEmax with increasing body weight. Dosage proportional to body surface area

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses.

Science.gov (United States)

Protasiewicz, Marcin; Rojek, Aleksandra; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research.

Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

CERN Document Server

Song, J H; Choi, W K

2002-01-01

The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

Regional citrate anticoagulation for continuous renal replacement therapy in severe burns-a retrospective analysis of a protocol-guided approach.

Science.gov (United States)

Gille, Jochen; Sablotzki, Armin; Malcharek, Michael; Raff, Thomas; Mogk, Martin; Parentin, Torsten

2014-12-01

For critically ill patients, the use of regional citrate anticoagulation as part of continuous renal replacement therapy (CRRT) has become increasingly common in recent years. However, there are scarce data on the use of this technique in patients with burns. The aim of this study was to examine the effectiveness, feasibility and complications of regional citrate anticoagulation for CRRT in burn patients, as well as the effects on coagulation and the electrolyte and acid-base balance. This retrospective study included all patients who received renal replacement therapy with citrate anticoagulation to treat acute kidney injury (AKI) between January 1, 2004 and December 31, 2009 at the burn unit of St. Georg Hospital GmbH in Leipzig. During the examination period, 18 patients were treated using CRRT with regional citrate anticoagulation (CVVHDF in the pre-dilution mode). The median patient age was 64 years (49.5; 71), with a median TBSA of 42.5% (33.25; 52.5) and a median ABSI score of 10 (9; 10). The CRRT was initiated on a median of 6 days (4; 8.75) after admission to the hospital and continued for a median duration of 7 days (5; 8). The median dialysis dose was 38.2mlkgBW(-1)h(-1) (31.8; 42.1). The median effective filter operation time was 67h (46; 72). No relevant disorders associated with acid-base balance, electrolytes or coagulation occurred, and there were no bleeding complications. In terms of bleeding risk and electrolyte and acid-base balance, regional citrate anticoagulation may be considered to be an effective, safe and user-friendly procedure for patients with severe burns and AKI. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Adherence to recommendations of the Therapeutic Positioning Report about treatment with oral anticoagulants in elderly patients with atrial fibrillation. The ESPARTA study.

Science.gov (United States)

Suárez Fernández, Carmen; Mostaza, Jose María; Castilla Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Cazorla, Daniel; Ràfols, Carles

2017-10-06

To evaluate the adherence to the recommendations in clinical practice performed by the Therapeutic Positioning Report (TPR) of the Spanish Agency of Medicines and Sanitary Products about the treatment with oral anticoagulants in patients aged≥75 years old with nonvalvular atrial fibrillation (NVAF) treated in Internal Medicine departments in Spain. Observational, cross-sectional and multicenter study in which 837 patients aged≥75 years old with NVAF, with stable treatment with oral anticoagulants at least 3 months before inclusion, and that had started treatment with oral anticoagulants before the inclusion period were included. Mean age was 83.0±5.0 years old, mean CHADS 2 score 3.2±1.2, mean CHA 2 DS 2 -VASc score 5.0±1.4, and mean HAS-BLED score 2.1±0.9. A percentage of 70.8 of patients were treated with vitamin K antagonists (VKA) and the rest of patients with direct oral anticoagulants (DOACs). A percentage of 65.6 of patients treated with VKA did not follow the recommendations made by the TPR compared with 43.0% of patients treated with DOACs (P<.0001). In the case of VKA, the main reason for being considered as not appropriate according to the TPR was having poor control of anticoagulation and not switching to DOACs, whereas in the case of DOACs, it was not receiving the adequate dose according to the TPR. In a high proportion of anticoagulated elderly patients with NVAF in Spain, the recommendations performed by the TPR are not followed, particularly with VKA, since patients are not switched to DOACs despite time in therapeutic range. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

A step toward development of printable dosage forms for poorly soluble drugs

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

2013-01-01

The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

Maths anxiety and medication dosage calculation errors: A scoping review.

Science.gov (United States)

Williams, Brett; Davis, Samantha

2016-09-01

A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of direct oral anticoagulants in the first year after market entry of edoxaban: A Danish nationwide drug utilization study.

Science.gov (United States)

Pottegård, Anton; Grove, Erik L; Hellfritzsch, Maja

2018-02-01

To describe the early uptake of edoxaban; the fourth direct oral anticoagulant (DOAC) to enter the market. Using the Danish nationwide health registries, we identified new users of edoxaban (n = 609) from June 6 (day of marketing) through June 2017. For comparison, we also identified new users of dabigatran (n = 2211), rivaroxaban (n = 19 227), and apixaban (n = 14 736). Users were described regarding indication of use, previous anticoagulant experience, comorbidity, and co-medication. The rate of edoxaban initiation increased to 2.0 per 100 000 person months in June 2017, compared with 6.3, 37.5, and 27.0 for dabigatran, rivaroxaban, and apixaban. Atrial fibrillation was the most common registered indication for edoxaban (67%) as well as the other DOACs (41-55%). Overall, users of edoxaban were comparable to users of other DOACs (median age 75 vs 72-76 years and 57% vs 53-59% males), except for a generally lower concomitant use of other drugs. Noticeably, 95% of edoxaban users had previously received anticoagulant treatment compared with 31% to 43% for new users of other DOACs, with 77% switching directly from another anticoagulant treatment to edoxaban (45% directly from VKA and 32% directly from DOACs). While the use of edoxaban is still limited compared with other DOACs, it is increasing. The majority of edoxaban users switch to edoxaban from other anticoagulant treatments. Continued monitoring of the utilization of DOACs, including effectiveness and safety, is considered essential to the safe and rational use of these drugs. Copyright © 2017 John Wiley & Sons, Ltd.

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

Science.gov (United States)

Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

2016-01-01

Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structural Analysis and Anticoagulant Activities of the Novel Sulfated Fucan Possessing a Regular Well-Defined Repeating Unit from Sea Cucumber

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Mingyi Wu

2015-04-01

Full Text Available Sulfated fucans, the complex polysaccharides, exhibit various biological activities. Herein, we purified two fucans from the sea cucumbers Holothuria edulis and Ludwigothurea grisea. Their structures were verified by means of HPGPC, FT-IR, GC–MS and NMR. As a result, a novel structural motif for this type of polymers is reported. The fucans have a unique structure composed of a central core of regular (1→2 and (1→3-linked tetrasaccharide repeating units. Approximately 50% of the units from L. grisea (100% for H. edulis fucan contain sides of oligosaccharides formed by nonsulfated fucose units linked to the O-4 position of the central core. Anticoagulant activity assays indicate that the sea cucumber fucans strongly inhibit human blood clotting through the intrinsic pathways of the coagulation cascade. Moreover, the mechanism of anticoagulant action of the fucans is selective inhibition of thrombin activity by heparin cofactor II. The distinctive tetrasaccharide repeating units contribute to the anticoagulant action. Additionally, unlike the fucans from marine alga, although the sea cucumber fucans have great molecular weights and affluent sulfates, they do not induce platelet aggregation. Overall, our results may be helpful in understanding the structure-function relationships of the well-defined polysaccharides from invertebrate as new types of safer anticoagulants.

Effect of Injection Minimal Dosages of Depot Medroxyprogesterone acetate (DMPA to Body Weight and Blood Chemistry Male Rat Strain Sprague-Dawley

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Nukman Moeloek

2009-11-01

Full Text Available Many family planning program focus more on men. Until now, vasectomy has been the commonly used method for male contraception. However, this method creates inconvenience such as irreversibility and psychological problems. One of the alternatives contraception is the combination of depot medroxyprogesterone acetate (DMPA and androgen. The minimum dosage of DMPA could suppress testosterone level that leads to reduced spermatogenesis and sperm viability. Nevertheless, until now it is not known whether minimum dosages of DMPA have an effect to body weight and blood chemistry. Therefore, this research aimed at determinate the effect of minimal dosages of DMPA to body mass and blood chemistry using male rats (Rattus norvegicus L. strain Sprague-Dawley as model. This research using completely randomized design, unequal size sample, castration treatments and several doses DMPA (1.25, 0.625, and 0.313 milligram. Injecting of DMPA conducted intramuscularly on week 0 and week 12. Normality/homogeneity Data normality were analyzed before ANOVA test. Then, abnormal data were tested using Kruskal-Wallis test. The result shows that injection of DMPA in various doses do not have an effect on body weight and blood chemistry such as erytrocytes, haemoglobin, hematocrite, HDL, LDL, total cholesterol, SGOT, SGPT and triglyseride (p>0,05. Furthermore, it is concluded that that no effect of minimal dosages of DMPA to body mass and blood chemistry of rat.

Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus.

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Sara Garamszegi

Full Text Available Ebola virus (EBOV infection in humans and non-human primates (NHPs is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1 CCAAT/enhancer-binding protein alpha, (2 tumor protein 53, and (3 megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection.

Demonstration of anticoagulation patient self-testing feasibility at an Indian Health Service facility: A case series analysis

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Schupbach RR

2013-03-01

Full Text Available Background: Anticoagulation patient self-testing (PST represents an alternative approach to warfarin monitoring by enabling patients to use coagulometers to test their international normalized ratio (INR values. PST offers several advantages that potentially improve warfarin management. Objective: To describe implementation and associated performance of a PST demonstration program at an Indian Health Service (IHS facility. Methods: A non-consecutive case series analysis of patients from a pharmacy-managed PST demonstration program was performed at an IHS facility in Oklahoma between July 2008 and February 2009.Results: Mean time in therapeutic range (TTR for the seven patients showed a small, absolute increase during the twelve weeks of PST compared to the twelve weeks prior to PST. Four of the seven patients had an increase in TTR during the twelve week course of PST compared to their baseline TTR. Three of four patients with increased TTR in the final eight week period of PST achieved a TTR of 100%. Of the three patients who experienced a decrease in TTR after initiating self-testing, two initially presented with a TTR of 100% prior to PST and one patient had a TTR of 100% for the final eight weeks of PST. The two patients not achieving a TTR of 100% during the twelve week PST period demonstrated an increase in TTR following the first four weeks of PST. Conclusion: Although anticoagulation guidelines now emphasize patient self-management (PSM only, optimal PST remains an integral process in PSM delivery. In the patients studied, the results of this analysis suggest that PST at the IHS facility provided a convenient, alternative method for management of chronic warfarin therapy for qualified patients. More than half of the patients demonstrated improvement in TTR. Although there is a learning curve immediately following PST initiation, the mean TTR for the entire PST period increased modestly when compared to the time period prior to PST.

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

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Evert Fuenmayor

2018-04-01

Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

Highlights from the IV International Symposium of Thrombosis and Anticoagulation (ISTA), October 20-21, 2011, Salvador, Bahia, Brazil.

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Lopes, Renato D; Becker, Richard C; Newby, L Kristin; Peterson, Eric D; Hylek, Elaine M; Granger, Christopher B; Crowther, Mark; Wang, Tracy; Carvalho, Antonio C; Berwanger, Otavio; Giraldez, Roberto R; Feitosa, Gilson Soares; Ribeiro, Jorge Pinto; Darze, Eduardo; Kalil, Renato A K; Andrande, Marianna; Boas, Fabio Villas; Andrade, Jadelson; Rocha, Ana Thereza; Harrington, Robert A; Lopes, Antonio C; Garcia, David A

2012-07-01

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Fourth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, from October 20-21, 2011. This scientific program was developed by clinicians for clinicians and was promoted by three major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, and Hospital do Coração Research Institute. Comprising 2 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Cost of vitamin K antagonist anticoagulant treatment in patients with metallic prosthetic valve in mitral position

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Gabriela Ene

2016-08-01

Full Text Available Background: The initiation of oral anticoagulation therapy after valve replacement surgery requires strict monitoring because these patients are at high risk for the development of thrombotic complications and present an increased risk of bleeding. Objectives: The aim of this study was to examine the total healthcare costs of oral anticoagulant treatment with vitamin K antagonists in patients with metallic prosthetic valves in the mitral position. Methods: Data from clinical records were used in the study including international normalized ratio results, number of medical visits, type of anticoagulant, use of rescue medication and hospital admissions from related complications. The drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included in the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the diagnosis-related group price for each case. Results: We collected data from 151 patients receiving oral anticoagulation therapy with vitamin K antagonist who were diagnosed with mitral prosthesis (n = 90, mitro-aortic prosthesis (n = 57, and mitral and tricuspid prosthesis (n = 4. The total direct healthcare cost was €15302.59, with a mean total cost per patient per year of €1558.15 (±2774.58 consisting of 44.38 (±42.30 for drug cost, €71.41 (±21.43 for international normalized ratio monitoring, €429.52 (±126.87 for medical visits, €26.31 (±28.38 for rescue medication and €986.53 (±2735.68 for related complications. Conclusion: Most direct healthcare costs associated with the sampled patients arose from the specialist-care monitoring required for treatment. Good monitoring is inversely related to direct healthcare costs.

THE PROBLEM OF THE USE OF NEW ORAL ANTICOAGULANTS IN CANCER PATIENTS RECEIVING CHEMOTHERAPY

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A. A. Rumyantsev

2015-09-01

Full Text Available Despite large number of known risk factors of venous thromboembolism (VTE in cancer patients existing prediction models do not allow definite identification of cancer patients that have indications for anticoagulant prevention. Besides, heparin and warfarin use for VTE prevention in cancer is accompanied by some problems. New oral anticoagulants (NOAC are promising drugs for use in oncology practice; however their use is complicated by the lack of data on efficacy and safety in these patients, potential drug interactions and the possibility of unpredictable changes in effect during chemotherapy. Widespread use of NOAC for the prevention and treatment of tumor-associated VTE prior to phase III trials is not recommended. However, the criteria for selection of patients for whom the study of the efficacy and safety of NOAC is a priority can now be developed.

THE PROBLEM OF THE USE OF NEW ORAL ANTICOAGULANTS IN CANCER PATIENTS RECEIVING CHEMOTHERAPY

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A. A. Rumyantsev

2014-01-01

Full Text Available Despite large number of known risk factors of venous thromboembolism (VTE in cancer patients existing prediction models do not allow definite identification of cancer patients that have indications for anticoagulant prevention. Besides, heparin and warfarin use for VTE prevention in cancer is accompanied by some problems. New oral anticoagulants (NOAC are promising drugs for use in oncology practice; however their use is complicated by the lack of data on efficacy and safety in these patients, potential drug interactions and the possibility of unpredictable changes in effect during chemotherapy. Widespread use of NOAC for the prevention and treatment of tumor-associated VTE prior to phase III trials is not recommended. However, the criteria for selection of patients for whom the study of the efficacy and safety of NOAC is a priority can now be developed.

The role of heparin in sepsis: much more than just an anticoagulant.

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Li, Xu; Ma, Xiaochun

2017-11-01

Despite progress in antibiotic treatment, mechanical ventilation, fluid resuscitation and blood glucose maintenance, sepsis remains a cause of high mortality in the intensive care unit to date, there are no proven treatment strategies for the routine management of septic patients. The extensive interaction between inflammation and coagulation contributes to the basic pathophysiology of sepsis. Thus, the agents that attenuate the activation of both inflammation and coagulation may improve the outcome in sepsis. Apart from the well-known anticoagulant effects of heparin, it also possesses various immunomodulatory properties and protects glycocalyx from shedding. Hence, heparin seems to be such an agent. Immunothrombosis plays an important role in early host defence against bacterial dissemination, thus the proper timing for anticoagulant therapy should be determined. We review the available experimental and clinical data supporting the use of heparin in sepsis. At this time the use of heparin in the treatment of sepsis is conflicting. Future trials of heparin therapy for sepsis should concentrate on the very severely ill patients, in whom benefit is most likely to be demonstrated. © 2017 John Wiley & Sons Ltd.

Statin use decreases coagulation in users of vitamin K antagonists.

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van Rein, Nienke; Biedermann, J S; Bonafacio, S M; Kruip, M J H A; van der Meer, F J M; Lijfering, W M

2016-12-01

The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs). We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test. Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower. Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

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Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

2014-02-01

Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

In vivo examination of the anticoagulant effect of the Brassica oleracea methanol extract

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Khan Rafeeq Alam

2015-01-01

Full Text Available The anticoagulant effect of the methanol extract of Brassica oleracea var. capitata (MEB was examined in rabbits. The animals were divided into five groups, each comprising seven animals. Three groups were administered increasing doses of MEB (200, 300, and 500 mg/kg, respectively; one group received warfarin (0.54 mg/kg; animals in the control group received saline (1 ml/day equivalent to the volume of doses applied to the treated and standard animals. Biochemical tests were performed on the 16th and 31st days of dosing. Animals that were administered MEB (500 mg MEB/kg 30 days displayed increases of 24.07 s, 28.79 s and 4.08 s in activated partial thromboplastin (aPTT, fibrinogen (Fg and thrombin time (TT. Compared to the control, the increase in aPTT and Fg was highly significant and the increase in TT was significant. The anticoagulant effect exhibited by MEB in rabbits may be due to inactivation or inhibition of factors affecting coagulation.

Pheochromocytoma diagnosed after anticoagulation for atrial fibrillation ablation procedure: a giant in disguise.

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Galvão Braga, Carlos; Ribeiro, Sílvia; Martins, Juliana; Arantes, Carina; Ramos, Vítor; Primo, João; Magalhães, Sónia; Correia, Adelino

2014-04-01

Pheochromocytoma is a rare catecholamine-producing tumor, discovered incidentally in 50% of cases. We present the case of a 44-year-old male with a history of paroxysmal palpitations. Baseline ECG, transthoracic echocardiogram and ECG stress test showed no relevant alterations. Paroxysmal atrial fibrillation was detected on 24-hour Holter ECG. After antiarrhythmic therapy, the patient remained symptomatic, and was accordingly referred for electrophysiological study and atrial fibrillation ablation. Anticoagulation was initiated before the procedure. After ablation and still anticoagulated, he complained of hematospermia. The abdominal and pelvic imaging study showed a 10-cm left adrenal mass, predominantly cystic, compatible with pheochromocytoma, which was confirmed after biochemical tests (increased urine metanephrines and plasma catecholamines). Metaiodobenzylguanidine scintigraphy scanning confirmed localized disease in the adrenal gland, excluding other uptake foci. Following appropriate preoperative management, surgical resection of the giant mass was performed successfully and without complications. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

OPTIONS FOR USE OF APPROPRIATE ANTICOAGULANT THERAPY IN PATIENTS WITH THERMAL INJURY WITH A HIGH RISK OF THROMBOEMBOLIC COMPLICATIONS DEVELOPMENT ASSOCIATED WITH RECURRENT INTESTINAL BLEEDING

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V. S. Borisov

2015-01-01

Full Text Available ABSTRACT. Patients with major thermal injury require anticoagulant therapy during almost the whole period of the burn disease, forcing the physician to balance constantly between the risk of possible bleeding associated with surgical treatment and the risk of thrombosis development in patients demonstrating a number of factors predisposing to the development of VTС. We report a clinical case of appropriate anticoagulant therapy using the new oral anticoagulants in a patient with a high risk of VTС development and recurrent bleeding from the tumor of the ascending colon. 

Adverse outcomes of anticoagulant use among hospitalized patients with chronic kidney disease: a comparison of the rates of major bleeding events between unfractionated heparin and enoxaparin.

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Fatemeh Saheb Sharif-Askari

Full Text Available BACKGROUND: Anticoagulation therapy is usually required in patients with chronic kidney disease (CKD for treatment or prevention of thromboembolic diseases. However, this benefit could easily be offset by the risk of bleeding. OBJECTIVES: To determine the incidence of adverse outcomes of anticoagulants in hospitalized patients with CKD, and to compare the rates of major bleeding events between the unfractionated heparin (UFH and enoxaparin users. METHODS: One year prospective observational study was conducted in patients with CKD stages 3 to 5 (estimated GFR, 10-59 ml/min/1.73 m(2 who were admitted to the renal unit of Dubai Hospital. Propensity scores for the use of anticoagulants, estimated for each of the 488 patients, were used to identify a cohort of 117 pairs of patients. Cox regression method was used to estimate association between anticoagulant use and adverse outcomes. RESULTS: Major bleeding occurred in 1 in 3 patients who received anticoagulation during hospitalization (hazard ratio [HR], 4.61 [95% confidence interval [CI], 2.05-10.35]. Compared with enoxaparin users, patients who received anticoagulation with unfractionated heparin had a lower mean [SD] serum level of platelet counts (139.95 [113] × 10(3/µL vs 205.56 [123] × 10(3/µL; P<0.001, and had a higher risk of major bleeding (HR, 4.79 [95% CI, 1.85-12.36]. Furthermore, compared with those who did not receive anticoagulants, patients who did had a higher in-hospital mortality (HR, 2.54 [95% CI, 1.03-6.25]; longer length of hospitalization (HR, 1.04 [95% CI, 1.01-1.06]; and higher hospital readmission at 30 days (HR, 1.79 [95% CI, 1.10-2.91]. CONCLUSIONS: Anticoagulation among hospitalized patients with CKD was significantly associated with an increased risk of bleeding and in-hospital mortality. Hence, intensive monitoring and preventive measures such as laboratory monitoring and/or dose adjustment are warranted.

Quality of anticoagulation therapy in neurological patients in a tertiary care hospital in north India

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Prabhat Singh

2016-01-01

Interpretation & conclusions: It may be concluded that stable therapeutic INR is difficult to maintain in neurological patients. Optimal modification of diet, drug and dose of oral anticoagulant may help in stabilization of INR.

Low-dosage helical CT applications for chest medical checkup and lung cancer screening

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Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

2005-01-01

Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma

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Vinholt, Pernille J; Nybo, Mads

2015-01-01

We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays...

Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction

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Potpara, Tatjana S; Ferro, Charles J; Lip, Gregory Y H

2018-01-01

Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly prevalent in the general population and share common risk factors such as older age, hypertension and diabetes mellitus. The presence of CKD increases the risk of incident AF, and, likewise, AF increases the risk of CKD de......, where appropriate, use of warfarin with good-quality anticoagulation control....

[Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care].

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Fernández López, P; López Ramiro, M I; Merino de Haro, I; Cedeño Manzano, G; Díaz Siles, F J; Hermoso Sabio, A

In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. The indication for anticoagulation is correct in our population, assuming a low-intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Is stopping of anticoagulant therapy really required in a minor dental surgery? - How about in an endodontic microsurgery?

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Yong-Wook Cho

2013-08-01

Full Text Available Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery.

Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis.

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Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

2016-01-21

Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, Pvenous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities.

Bivalirudin for Pediatric Procedural Anticoagulation: A Narrative Review.

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Zaleski, Katherine L; DiNardo, James A; Nasr, Viviane G

2018-02-14

Bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ), a direct thrombin inhibitor, has found increasing utilization as a heparin alternative in the pediatric population, most commonly for the treatment of thrombosis secondary to heparin-induced thrombocytopenia. Due to the relative rarity of heparin-induced thrombocytopenia as well as the lack of Food and Drug Administration-approved indications in this age group, much of what is known regarding the pharmacokinetics and pharmacodynamics of bivalirudin in this population has been extrapolated from adult data. This narrative review will present recommendations regarding the use of bivalirudin for procedural anticoagulation in the pediatric population based on the published literature.

QR encoded smart oral dosage forms by inkjet printing.

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Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

2018-01-30

The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study.

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Piazza, Gregory; Mani, Venkatesh; Goldhaber, Samuel Z; Grosso, Michael A; Mercuri, Michele; Lanz, Hans J; Schussler, Steven; Hsu, Ching; Chinigo, Amy; Ritchie, Bruce; Nadar, Venkatesh; Cannon, Kevin; Pullman, John; Concha, Mauricio; Schul, Marlin; Fayad, Zahi A

2016-08-01

The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14-21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a 'bridge' to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14-21 was similar in patients treated with edoxaban and parenteral anticoagulation as a 'bridge' to warfarin (-50.1% vs -58.9%; 95% confidence interval of treatment difference, -12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens.ClinicalTrials.gov IDENTIFIER NCT01662908: INVESTIGATIONAL NEW DRUG IND APPLICATION EDOXABAN IND # 63266. © The Author(s) 2016.

An Easy Method to Eliminate the Effect of Lupus Anticoagulants in the Coagulation Factor Assay.

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Tang, Ning; Yin, Shiyu

2016-07-01

To build and evaluate intrinsic coagulation factor assays which can eliminate the effect of lupus anticoagulants (LAC). Commercial silica clotting time confirmatory (SCT-C) reagent containing sufficient synthetic phospholipid and routine activated partial thromboplastin time (APTT) reagent were each used for one-stage detection of FVIII, FIX, and FXI activities, in samples with or without LAC, and the results were compared. For samples without LAC, consistent results of FVIII, FIX, and FXI using both SCT-C reagent and APTT reagent were obtained. For samples with LAC, the assays with SCT-C reagent not only could eliminate the effect of strong lupus anticoagulants but also needed fewer dilutions than that with routine APTT reagent. The intrinsic factor detections by SCT-C reagent are credible and convenient to be used for samples with LAC.

Anticoagulant activity in salivary glands of the insect vector Culicoides variipennis sonorensis by an inhibitor of factor Xa.

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Pérez de León, A A; Valenzuela, J G; Tabachnick, W J

1998-02-01

Blood feeding by the insect vector Culicoides variipennis sonorensis involves laceration of superficial host tissues, an injury that would be expected to trigger the coagulation cascade. Accordingly, the salivary glands of C.v. sonorensis were examined for the presence of an antihemostatic that prevents blood coagulation. Assays using salivary gland extracts showed a delay in the recalcification time of plasma devoid of platelets, indicating the presence of anticoagulant activity. Retardation in the formation of a fibrin clot was also observed after the addition of tissue factor to plasma that was preincubated with salivary gland extracts. Similarly, an inhibitory effect by salivary gland extracts was detected in assays that included factors of the intrinsic pathway. Inhibition of the catalytic activity of purified factor Xa toward its chromogenic substrate suggested that it was the target of the salivary anticoagulant of C.v. sonorensis. This was corroborated by the coincidence of anticoagulant and anti-FXa activities obtained by reverse-phase HPLC. The depletion of anti-FXa activity from salivary glands during blood feeding suggests that the FXa inhibitor functions as anticoagulant. Molecular sieving HPLC yielded an apparent molecular mass of 28 kDa for the salivary FXa inhibitor of C.v. sonorensis. Preventing the formation of thrombin through the inhibition of FXa likely facilitates blood feeding by maintaining the pool of blood fluid at the feeding site. The salivary FXa inhibitor of C.v. sonorensis could impair the network of host-defense mechanisms in the skin microenvironment by avoiding blood coagulation at the site of feeding.

Dosage-based parameters for characterization of puff dispersion results.

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Berbekar, Eva; Harms, Frank; Leitl, Bernd

2015-01-01

A set of parameters is introduced to characterize the dispersion of puff releases based on the measured dosage. These parameters are the dosage, peak concentration, arrival time, peak time, leaving time, ascent time, descent time and duration. Dimensionless numbers for the scaling of the parameters are derived from dimensional analysis. The dimensionless numbers are tested and confirmed based on a statistically representative wind tunnel dataset. The measurements were carried out in a 1:300 scale model of the Central Business District in Oklahoma City. Additionally, the effect of the release duration on the puff parameters is investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Do Age and Anticoagulants Affect the Natural History of Acute Subdural Hematomas?

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Lucke-Wold, Brandon P.; Turner, Ryan C.; Josiah, Darnell; Knotts, Chelsea; Bhatia, Sanjay

2016-01-01

Acute subdural hematoma is a serious complication following traumatic brain injury. Large volume hematomas or those with underlying brain injury can cause mass effect, midline shift, and eventually herniation of the brain. Acute subdural hematomas in the young are associated with high-energy trauma and often have underlying contusions, while acute subdural hematomas in the elderly are associated with minor trauma and an absence of underlying contusions, even though the elderly are more likely to be on anticoagulants or anti-platelet therapy. In the young patients with high impact injuries the hematomas tend to be small and the underlying brain injury and swelling is responsible for the increased intracranial pressure and midline shift. In the elderly, the injuries are low impact (e.g fall from standing), the underlying brain is intact, and the volume of the hematoma itself produces symptoms. In addition the use of anticoagulants and antiplatelet agents in the elderly population has been thought to be a poor prognostic indicator and is considered to be responsible for larger hematomas and poor outcome. When managed conservatively, acute subdural hematomas can sometimes progress to chronic subdural hematoma formation, further enlargement, seizures, and progressive midline shift. Another potential difference in the young and the elderly is brain atrophy, which increases the potential space to accommodate a larger hematoma. It is not known if these two groups differ in other ways that might have implications for treatment or prognosis. In this paper, we investigate the clinical course of 80 patients admitted to our institution with acute subdural hematomas, to identify differences in patients above or below the age of 65 years. The natural progression/resolution of acute subdural hematomas was mapped by measuring volume expansion/regression over time. In this retrospective chart review, we investigated clinical baseline metrics and subsequent volumetric expansion

Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

African Journals Online (AJOL)

Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

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Wang, Christina Hao; Rubinsky, Anna D; Minichiello, Tracy; Shlipak, Michael G; Price, Erika Leemann

2018-05-31

Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle. We compared cystatin C-based eGFR (eGFR cys ) with multiple creatinine-based estimates of kidney function in hospitalized patients receiving anticoagulants, to assess for discordant results that could impact medication dosing. Retrospective chart review of hospitalized patients over 1 year who received non-vitamin K antagonist anticoagulation, and who had same-day measurements of cystatin C and creatinine. Seventy-five inpatient veterans (median age 68) at the San Francisco VA Medical Center (SFVAMC). We compared the median difference between eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation using cystatin C (eGFR cys ) and eGFRs using three creatinine-based equations: CKD-EPI (eGFR EPI ), Modified Diet in Renal Disease (eGFR MDRD ), and Cockcroft-Gault (eGFR CG ). We categorized patients into standard KDIGO kidney stages and into drug-dosing categories based on each creatinine equation and calculated proportions of patients reclassified across these categories based on cystatin C. Cystatin C predicted overall lower eGFR compared to creatinine-based equations, with a median difference of - 7.1 (IQR - 17.2, 2.6) mL/min/1.73 m 2 versus eGFR EPI , - 21.2 (IQR - 43.7, - 8.1) mL/min/1.73 m 2 versus eGFR MDRD , and - 25.9 (IQR - 46.8, - 8.7) mL/min/1.73 m 2 versus eGFR CG . Thirty-one to 52% of patients were reclassified into lower drug-dosing categories using cystatin C compared to creatinine-based estimates. We found substantial discordance in eGFR comparing cystatin C with creatinine in this group of anticoagulated inpatients. Our sample size was limited and included few women. Further

Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin

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Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito

2018-01-01

Objectives This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)–associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. Methods We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. Results DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). Conclusions This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. PMID:29490916

O-sulfated bacterial polysaccharides with low anticoagulant activity inhibit metastasis.

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Borgenström, Marjut; Wärri, Anni; Hiilesvuo, Katri; Käkönen, Rami; Käkönen, Sanna; Nissinen, Liisa; Pihlavisto, Marjo; Marjamäki, Anne; Vlodavsky, Israel; Naggi, Annamaria; Torri, Giangiacomo; Casu, Benito; Veromaa, Timo; Salmivirta, Markku; Elenius, Klaus

2007-07-01

Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. COLI K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.

Safety, efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: a propensity score matching analysis

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Jung Wha Chung

2014-12-01

Full Text Available Background/AimsPortal-vein thrombosis (PVT develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients.MethodsPatients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE. Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment, and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography.ResultsTwenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5 compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation.ConclusionsWarfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation.

X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

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Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

2011-03-03

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

The influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of Platelet Rich Plasma (PRP

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Lilies Anggarwati Astuti

2016-06-01

Full Text Available Platelet Rich Plasma (PRP is a blood concentrate that has a thrombocytes concentration several time higher than normal concentration of thrombocytes in normal human blood. PRP is a promising alternative to surgery with a safe and natural healing. The standard protocol for PRP preparation must be determined to get the right quantity and quality of the matrix of fibrin, leukocytes, platelets and growth factors. It could not be separated from the number of PRP produced. The use of PRP in the success of periodontal treatment would not be separated from methods to obtain it. To detect the influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of PRP. There are 41 subjects studied by taking 21 ml of venous blood in each of the seven tubes. Centrifugation performed twice with different speed, duration, use of anticoagulants then analyzed. This quantity between the two groups differed significantly between the PRP in EDTA group is higher 322.2 ml rather than citrate acid 3.8% group, then control group is higher 329.5 ml rather than citrate acid 3.8% group, while there is no difference between EDTA and control group. There is effect of the use of anticoagulants EDTA compared with citrate acid 3.8% in the quantity of PRP, and there was no effect using citrate acid 3.8% as anticoagulants in quantity of PRP.

Highlights from the Tenth International Symposium of Thrombosis and Anticoagulation (ISTA X), September 22 and 23, 2017, Salvador, Bahia, Brazil.

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Lopes, Renato D; Guimarães, Patricia O; Crowther, Mark; Hylek, Elaine; Feitosa-Filho, Gilson S; Ritt, Luiz E; Filgueiras, Nivaldo; Garcia, David A

2018-05-01

To discuss and share knowledge about advances in the care of patients with thrombotic disorders, the Tenth International Symposium of Thrombosis and Anticoagulation was held in Salvador, Bahia, Brazil, on September 22 and 23, 2017. This scientific program was developed by clinicians for clinicians and was promoted by two major clinical research institutes-the Brazilian Clinical Research Institute and the Duke Clinical Research Institute of the Duke University School of Medicine. Comprising academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Management of Anticoagulation for Portal Vein Thrombosis in Individuals with Cirrhosis: A Systematic Review

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Geneviève Huard

2012-01-01

Full Text Available Non-neoplastic portal vein thrombosis (PVT is an increasingly recognized complication of liver cirrhosis. It is often diagnosed fortuitously and can be either partial or complete. The clinical significance of PVT is not obvious except in some situations such as when patients are on the waiting list for liver transplantation. The only known therapy is anticoagulation which has been shown to permit the disappearance of thrombosis and to prevent further extension. Anticoagulation is a challenging therapy in individuals with liver cirrhosis because of the well-recognized coagulation abnormalities observed in that setting and because of the increased risk of bleeding, especially from gastrointestinal tract caused by portal hypertension. We herein review the current knowledge on that topic in order to highlight the advantages and disadvantages of the currently proposed therapeutic attitudes in face of the diagnosis of PVT in individuals with cirrhosis.

Ammonia concentrations in canine whole blood, EDTA-anticoagulated whole blood, and plasma measured by use of a point-of-care ammonia meter.

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Odunayo, Adesola; Tobias, Karen M; Okafor, Chika C; Flatland, Bente

2017-11-01

OBJECTIVE To investigate the use of canine whole blood (WB) for measurement of ammonia concentration by use of a point-of-care ammonia meter and to compare results of measuring ammonia concentrations in WB, EDTA-anticoagulated WB, and plasma. ANIMALS 40 client-owned dogs. PROCEDURES A blood sample (2 mL) was obtained from each dog. One drop of WB was immediately applied to a test strip for evaluation with an ammonia meter. The remainder of the blood sample was placed in an EDTA-containing tube, and 1 drop of EDTA-anticoagulated WB was applied to a test strip. The remaining EDTA-anticoagulated WB sample was centrifuged, and the plasma was harvested and placed on ice. One drop of plasma was applied to a test strip; the remainder of the plasma sample was transported on ice and used for ammonia measurement with a reference laboratory instrument. All samples were tested within 1 hour after sample collection. Results were evaluated to detect significant differences in ammonia concentration. RESULTS Ammonia concentrations did not differ significantly between WB and EDTA-anticoagulated WB and between plasma samples measured with the meter and reference laboratory instrument. However, median ammonia concentration was significantly higher in plasma than in WB or EDTA-anti-coagulated WB. CONCLUSIONS AND CLINICAL RELEVANCE Anticoagulant-free WB was a valid sample for measurement by use of the ammonia meter. Plasma samples had higher ammonia concentrations than did WB samples. Results for each sample type should be interpreted by use of specimen- and method-specific reference intervals.

Treatment Adherence as a New Choice Factor for Optimization of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation and Hemostatic Gene Polymorphisms

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Yu. P. Skirdenko

2016-01-01

Full Text Available Aim. To evaluate treatment adherence and prevalence of CYP2C9 and VKORC1 gene mutations in patients with atrial fibrillation (AF and provide rationale of choice for oral anticoagulation therapy.Material and methods. Treatment adherence was evaluated in 137 AF patients (aged 35-85 years with quantitative estimation of drug therapy adherence along with compliance to medical support and lifestyle modifications. Among them 82 patients underwent polymerase chain reaction (PCR analysis of CYP2C9 and VKORC1 gene polymorphisms.Results. Patients receiving anticoagulation therapy are characterized by lower level of adherence compared to patients without anticoagulants (65.2±19.3% vs 68.5±19.1%; Wald-Wolfowitz; p<0.05. Considering all studied parameters men are less adherent than women (54.7±18.6% vs 60.6±16.7%; Kolmogorov-Smirnov; p<0.05. Patients receiving new oral anticoagulants (NOAC have better compliance compared with patients of warfarin group. Mutations in CYP2C9 gene were detected in 32.9%, VKORC1 – in 68.3%, and their combination – in 21.9% of study participants. Warfarin therapy may be potentially dangerous in such patients due to low adherence.Conclusion. Considering high prevalence of CYP2C9 and VKORC1 gene mutations treatment adherence should be estimated to optimize choice of anticoagulation therapy. NOAC treatment should be considered in patients with low adherence for prevention of thromboembolic complications.

The Role of Program Directors in Treatment Practices: The Case of Methadone Dose Patterns in U.S. Outpatient Opioid Agonist Treatment Programs.

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Frimpong, Jemima A; Shiu-Yee, Karen; D'Aunno, Thomas

2017-10-01

To describe changes in characteristics of directors of outpatient opioid agonist treatment (OAT) programs, and to examine the association between directors' characteristics and low methadone dosage. Repeated cross-sectional surveys of OAT programs in the United States from 1995 to 2011. We used generalized linear regression models to examine associations between directors' characteristics and methadone dose, adjusting for program and patient factors. Data were collected through telephone surveys of program directors. The proportion of OAT programs with an African American director declined over time, from 29 percent in 1995 to 16 percent in 2011. The median percentage of patients in each program receiving role in explaining variations in methadone dosage across programs and patients. Further research should investigate the causal pathways through which directors' characteristics affect treatment practices. This may lead to new, multifaceted managerial interventions to improve patient outcomes. © Health Research and Educational Trust.

The anticoagulant effect of therapeutic levels of dabigatran in atrial fibrillation evaluated by thrombelastography (TEG®), Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT)

DEFF Research Database (Denmark)

Solbeck, Sacha; Jensen, Annette Schophuus; Maschmann, Christian

2018-01-01

 min), mean dabigatran concentration of 179.2 ng/mL by HTI (range 26-687 ng/mL) and by ECT 225.1 ng/mL (range 42-1020 ng/mL). The two dosage groups had comparable anticoagulation demonstrated by equally prolonged TEG® R (p = .909), HTI (p = .707) and ECT (p = .567). No difference in creatinine levels...... Time (ECT) in patients with non-valvular atrial fibrillation (NVAF). Blood samples from 35 AF patients receiving either 110 mg (n 19) or 150 mg (n 16) dabigatran twice daily were analyzed with TEG®, HTI and ECT 2-3 h after dabigatran intake. All patients had prolonged TEG® R. The patients receiving...... dabigatran 110 mg ×2 had a TEG® R mean 14.2 min (range 9.1-25), a mean dabigatran concentration measured by HTI of 268.5 ng/mL (range 54-837 ng/mL) and by ECT of 355.7 ng/mL (range 40-1020 ng/mL). The corresponding numbers for patients receiving dabigatran 150 mg ×2 were TEG® R mean of 12.5 min (range 9.2-23.2...

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

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Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

The impact of pre-injury direct oral anticoagulants compared to warfarin in geriatric G-60 trauma patients.

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Barletta, J F; Hall, S; Sucher, J F; Dzandu, J K; Haley, M; Mangram, A J

2017-08-01

Pre-injury oral anticoagulants are associated with worse outcomes in geriatric (G-60) trauma patients, but there are limited data comparing warfarin with direct oral anticoagulants (DOAC). We sought to compare outcomes in G-60 trauma patients taking pre-injury DOACs vs. warfarin. All trauma patients, age ≥60 who were admitted to the hospital and taking an oral anticoagulant pre-injury were retrospectively identified. Patients were excluded if their reason for admission was a suicide attempt or penetrating extremity injury. Outcome measures included blood transfusions, hospital LOS, and mortality. A second analysis was performed, whereby patients were matched using ISS and age. There were 3,941 patients identified; 331 had documentation of anticoagulant use, pre-injury (warfarin, n = 237; DOAC, n = 94). Demographics were similar, but ISS [9 (4-13) vs. 8 (4-9), p = .027], initial INR [2.2 (1.8-2.9) vs. 1.2 (1.1-1.5), p warfarin group. There was no difference in the use of blood transfusions (24 vs. 17%, p = .164) or mortality (5.9 vs. 4.3%, p = .789) between warfarin and DOAC groups, respectively. However, LOS was longer in the warfarin group [5 (3-7.5) vs. 4 (2-6.3) days, p = .02]. Matched analysis showed no difference in blood transfusions (23 vs. 17%, p = .276), mortality (2.1 vs. 4.3%, p = .682) or LOS [5 (3-7) vs. 4 (2-6.3) days, p = .158] between warfarin and DOAC groups, respectively. Pre-injury DOACs are not associated with worse clinical outcomes compared to warfarin in G-60 trauma patients. Higher use of pharmacologic reversal agents with warfarin may be related to differences in mechanism of action and effect on INR.

The practical management of bleedings during treatment with direct oral anticoagulants: the emergency reversal therapy

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Luca Masotti

2013-12-01

Full Text Available Bleeding represents the most feared complication of the new oral anticoagulants, direct oral anticoagulants (DOACs, as well as all the antithrombotic therapies. During the acute phase of bleeding in patients taking anticoagulants, restoration of an effective hemostasis represents the cornerstone of practical management. While vitamin K antagonists are effectively and promptly reversed by specific antidotes such as prothrombin complex concentrates (PCCs, fresh frozen plasma or vitamin K, it is still not clear how to manage the urgent reversal of DOACs during life-threatening or major bleedings due to the lack of specific antidotes. However, in vitro and ex vivo studies have suggested some potential strategies to reverse DOACs in clinical practice, other than general support measures that are always recommended. Activated charcoal could be used in subjects with DOAC-related bleedings presenting to the emergency department within two hours of the last oral intake. Non-activated or activated PCCs (FEIBA and recombinant activated Factor VII (raFVII seem to be the optimal strategy for urgent reversal of dabigatran, while non-activated PCCs seem to have efficacy in reversing rivaroxaban. Due to its low plasma protein binding, dabigatran could be also dialyzed in urgent cases. Clinically relevant non-major bleedings and minor bleedings should be treated with general and local measures, respectively, and, when necessary, with dose delay or drug withdrawal. In this article, the Authors describe the practical approach to bleedings occurring during DOACs treatment.

Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art.

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Thaler, Johannes; Pabinger, Ingrid; Ay, Cihan

2015-01-01

Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.

Neuraxial and peripheral nerve blocks in patients taking anticoagulant or thromboprophylactic drugs: challenges and solutions

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Li J

2015-08-01

Full Text Available Jinlei Li, Thomas Halaszynski Department of Anesthesiology, Yale University, Yale New Haven Hospital, New Haven, CT, USA Abstract: Incidence of hemorrhagic complications from neuraxial blockade is unknown, but classically cited as 1 in 150,000 epidurals and 1 in 220,000 spinals. However, recent literature and epidemiologic data suggest that for certain patient populations the frequency is higher (1 in 3,000. Due to safety concerns of bleeding risk, guidelines and recommendations have been designed to reduce patient morbidity/mortality during regional anesthesia. Data from evidence-based reviews, clinical series and case reports, collaborative experience of experts, and pharmacology used in developing consensus statements are unable to address all patient comorbidities and are not able to guarantee specific outcomes. No laboratory model identifies patients at risk, and rarity of neuraxial hematoma defies prospective randomized study so “patient-specific” factors and “surgery-related” issues should be considered to improve patient-oriented outcomes. Details of advanced age, older females, trauma patients, spinal cord and vertebral column abnormalities, organ function compromise, presence of underlying coagulopathy, traumatic or difficult needle placement, as well as indwelling catheter(s during anticoagulation pose risks for significant bleeding. Therefore, balancing between thromboembolism, bleeding risk, and introduction of more potent antithrombotic medications in combination with regional anesthesia has resulted in a need for more than “consensus statements” to safely manage regional interventions during anticoagulant/thromboprophylactic therapy. Keywords: antithrombotics, novel oral anticoagulant, regional, neurologic dysfunction, hematoma, peripheral nerve blockade

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary.

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Steffel, Jan; Verhamme, Peter; Potpara, Tatjana S; Albaladejo, Pierre; Antz, Matthias; Desteghe, Lien; Georg Haeusler, Karl; Oldgren, Jonas; Reinecke, Holger; Roldan-Schilling, Vanessa; Rowell, Nigel; Sinnaeve, Peter; Collins, Ronan; Camm, A John; Heidbüchel, Hein

2018-03-19

The current manuscript is the Executive Summary of the second update to the original Practical Guide, published in 2013. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF), and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to co-ordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are (i) eligibility for NOACs; (ii) practical start-up and follow-up scheme for patients on NOACs; (iii) ensuring adherence to prescribed oral anticoagulant intake; (iv) switching between anticoagulant regimens; (v) pharmacokinetics and drug-drug interactions of NOACs; (vi) NOACs in patients with chronic kidney or advanced liver disease; (vii) how to measure the anticoagulant effect of NOACs; (viii) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (ix) how to deal with dosing errors; (x) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (xi) management of bleeding under NOAC therapy; (xii) patients undergoing a planned invasive procedure, surgery or ablation; (xiii) patients requiring an urgent surgical intervention; (xiv) patients with AF and coronary artery disease; (xv) avoiding confusion with NOAC dosing across indications; (xvi) cardioversion in a NOAC-treated patient; (xvii) AF patients presenting with acute stroke while on NOACs; (xviii) NOACs in special

Optimal duration of anticoagulation. Provoked versus unprovoked VTE and role of adjunctive thrombophilia and imaging tests.

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Prandoni, Paolo; Barbar, Sofia; Milan, Marta; Campello, Elena; Spiezia, Luca; Piovella, Chiara; Pesavento, Raffaele

2015-06-01

Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years after a first episode is consistently around 30%. This risk is higher in patients with unprovoked than in those with (transient) provoked VTE, and among the latter in patients with medical than in those with surgical risk factors. Baseline parameters that have been found to be related to the risk of recurrent VTE are the proximal location of deep-vein thrombosis, obesity, old age, male sex and non-0 blood group, whereas the role of inherited thrombophilia is controversial. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer and the early development of the post-thrombotic syndrome. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify subjects in whom anticoagulation can be safely discontinued. Moreover, new opportunities are offered by a few emerging anti-Xa and anti-IIa oral compounds, which are likely to induce fewer haemorrhagic complications than vitamin K antagonists while preserving the same effectiveness; and by low-dose aspirin, which has the potential to prevent the occurrence of both venous and arterial thrombotic events.

Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.

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Charoo, Naseem; Cristofoletti, Rodrigo; Graham, Alexandra; Lartey, Paul; Abrahamsson, Bertil; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-12-01

Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide therapeutic index. BE of test formulations from many different manufacturers containing different excipients confirmed that the risk of bioinequivalence because of formulation and manufacturing factors is low. It was inferred that risk can be further reduced if in vitro studies are performed according to biowaiver guidelines. Thus, it is concluded that a biowaiver can be recommended for fluconazole IR dosage forms if (a) fluconazole is present as polymorphic form II or III or any other form/mixture showing high solubility, (b) the selection of excipients be limited to those found in IR drug products approved in International Conference on Harmonisation (ICH) countries for the same dosage form and used in their usual amounts, and (c) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving throughout the shelf life with similar dissolution profiles at pH 1.2, 4.5, and 6.8. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

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Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Accelerated in vitro release testing methods for extended release parenteral dosage forms

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Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

Single-Molecular Imaging of Anticoagulation Factor I from Snake Venom by Atomic Force Microscopy

Institute of Scientific and Technical Information of China (English)

XU,Xiao-Long(徐小龙); ZHOU,Yun-Shen(周云申); LIU,Qing-Liang(刘清亮); HOU,Jian-Guo(侯建国); YANG,Jing-Long(杨金龙); XIE,Yong-Shu(解永树)

2002-01-01

Anticoagulation factor I (ACF I) from the venom of Agkistrodon acutus is a binding protein to activated coagulation factor X (FXa) and possesses marked anticoagulant activity. Single ACF I molecule has been successfully imaged in air by tapping mode atomic force microscopy (AFM) with high-resolution using glutaraldehyde as a coupling agent. The physical adsorption and covalent binding of ACF I onto the mica show very different surface topographies. The former exhibits the characteristic strand-like structure with much less reproducibility, the latter displays a elliptic granular structure with better reproducibility, which suggests that the stability of ACF I molecules on the mica is enhanced by covalent bonding in the presence of glutaraldehyde. A small-scale AFM amplitude-mode image clearly shows that the covalently bonded ACF I molecule by glutaraldehyde has olive shape structure with an average size of 7.4 nm× 3.6 nm × 3.1 nm, which is very similar to the size determined from the crystal structure of ACF I.

Era of liver transplantation: combined anatomic splenectomy and anticoagulant therapy in prevention of portal vein thrombosis after splenectomy.

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Hongwei, Chen; Zhang, Liang; Maoping, Li; Yong, Zhang; Chengyou, Du; Dewei, Li

2015-01-01

Portal vein thrombosis (PVT) is a common complication following splenectomy in patients with liver cirrhosis and portal hypertension, which also brings difficulties to future possible liver transplantation. This paper retrospectively analyzes the preventive effect of combined anatomic splenectomy and early anticoagulant therapy on post-splenectomy portal vein thrombosis in patients with portal hypertension. We retrospectively analyzed 136 patients who underwent splenectomy at our hospital between January 2010 and December 2013 due to liver cirrhosis and portal hypertension. Patient conditions, such as coagulation function, splenic and portal vein thrombosis, intra-abdominal hemorrhage, pancreatic leakage and intra-abdominal infections, are observed postoperatively. Despite the presence of liver cirrhosis and portal hypertension in patients, early postoperative anticoagulant therapy has no significant impact on coagulation function and intra-abdominal hemorrhage of these patients (p > 0.05). Anatomic splenectomy can reduce the occurrence of complications such as postoperative bleeding, pancreatic leakage and intra-abdominal infections (p splenectomy and early postoperative anticoagulant therapy can reduce post-splenectomy portal vein thrombosis in patients with portal hypertension, and is conducive to the future liver transplantation therapy may be needed by the patients.

Spontaneous sublingual and intramural small-bowel hematoma in a patient on oral anticoagulation

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Mohamed Moftah

2012-08-01

Full Text Available Spontaneous sublingual hematoma and intramural small bowel hematoma are rare and serious complications of anticoagulant therapy. Though previously reported individually, there has been no previous report of the same two complications occurring in a single patient. A 71-year-old Caucasian man, who was on warfarin for atrial fibrillation, presented with difficulty in swallowing due to a sublingual hematoma. He was observed in our intensive care unit, his warfarin was held and he recovered with conservative management. He represented two months later with a two day history of abdominal pain and distension. An abdominopelvic computed tomography (CT scan now showed small bowel obstruction due to intramural small bowel hematoma and haemorrhagic ascites. Again, this was treated expectantly with a good outcome. In conclusion, life threatening haemorrhagic complications of oral anticoagulant therapy can recur. Conservative treatment is successful in most cases, but an accurate diagnosis is mandatory to avoid unnecessary surgery. CT scan is the investigation of choice for the diagnosis of suspected haemorrhagic complications of over coagulation.

Effect of regional citrate anticoagulation on critical patients with continuous renal replacement therapy

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Li-Li You

2016-12-01

Full Text Available Objective: To investigate the efficacy and safety of regional citrate anticoagulation (RCA in continuous renal replacement therapy (CRRT for critical patients. Methods: A total of 83 critical patients need CRRT in the intensive care units of our hospital from July 2012 to June 2016 were recruited in the study, and the patients were divided into two groups randomly, the patients in observation group received the RCA treatment, and the patients in control group received traditional low molecular heparin anticoagulation. The difference of safety indicators, biochemical indicators, extracorporeal circulation blood coagulation condition and complications in patients were determined between two groups. Results: Compared with control group, the patients in observation group had an elevated level of iCa2+, the level of chloride ion reduced, the use time of filter increased, the bleeding cases reduced, the concentrations of urea nitrogen, creatinine TNF-α , IL-1β, IL-8 and NO were all significantly downregulated, the data have a significant difference (P < 0.05. Conclusions: RCA is a safe and effective method for CRRT in patients with a high risk of bleeding.

Comparison of pre-filter and post-filter ionised calcium monitoring in continuous veno-venous hemodiafiltration (CVVHD-F with citrate anti-coagulation.

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Matthew J Brain

Full Text Available It is widespread practice during citrate anticoagulated renal replacement therapy to monitor circuit ionised calcium (iCa2+ to evaluate the effectiveness of anticoagulation. Whether the optimal site to sample the blood path is before or after the haemofilter is a common question.Using a prospectively collected observational dataset from intensive care patients receiving pre-dilution continuous veno-venous haemodiafiltration (CVVHD-F with integrated citrate anticoagulation we compared paired samples of pre and post filter iCa2+ where the target range was 0.3-0.5 mmol.L-1 as well as concurrently collected arterial iCa2+. Two nested mixed methods linear models were fitted to the data describing post vs pre filter iCa2+, and the relationship of pre, post and arterial samples.An 11 bed general intensive care unit.450 grouped samples from 152 time periods in seven patients on CRRT with citrate anticoagulation.The relationship of post to pre-filter iCa2+ was not 1:1 with post = 0.082 + 0.751 x pre-filter iCa2+ (95% CI intercept: 0.015-0.152, slope 0.558-0.942. Variation was greatest between patients rather than between circuits within the same patient or citrate dose. Compared to arterial iCa2+ there was no significant difference between pre and post-filter sampling sites (F-value 0.047, p = 0.827.These results demonstrate that there is minimal difference between pre and post filter samples for iCa2+ monitoring of circuit anticoagulation in citrate patients relative to the arterial iCa2+ in CVVHD-F however compared to pre-filter sampling, post filter sampling has a flatter response and greater variation.

Biowaiver monograph for immediate-release solid oral dosage forms: bisoprolol fumarate.

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Charoo, Naseem A; Shamsher, Areeg A A; Lian, Lai Y; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James; Shah, Vinod P; Dressman, Jennifer

2014-02-01

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate-release (IR) solid oral dosage forms containing bisoprolol as the sole active pharmaceutical ingredient (API) are reviewed. Bisoprolol is classified as a Class I API according to the current Biopharmaceutics Classification System (BCS). In addition to the BCS class, its therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions, and reported BE/bioavailability problems are taken into consideration. Qualitative compositions of IR tablet dosage forms of bisoprolol with a marketing authorization (MA) in ICH (International Conference on Harmonisation) countries are tabulated. It was inferred that these tablets had been demonstrated to be bioequivalent to the innovator product. No reports of failure to meet BE standards have been made in the open literature. On the basis of all these pieces of evidence, a biowaiver can currently be recommended for bisoprolol fumarate IR dosage forms if (1) the test product contains only excipients that are well known, and used in normal amounts, for example, those tabulated for products with MA in ICH countries and (2) both the test and comparator dosage form are very rapidly dissolving, or, rapidly dissolving with similarity of the dissolution profiles demonstrated at pH 1.2, 4.5, and 6.8. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

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Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

Patterns of direct oral anticoagulant drug prescription in France in 2010-2013: a study in the Midi-Pyrénées area.

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Diaz, Hugo; Bagheri, Haleh; Palmaro, Aurore; Rousseau, Vanessa; Bourrel, Robert; Montastruc, Jean-Louis; Birebent, Jordan

2018-03-27

The aim of our study was to study the pattern of prescription of direct-acting oral anticoagulants (DOACs) according to the French recommendations. We performed a cross-sectional study using anonymous data of patients covered by the French National Health Insurance information system (SNIIRAM) from 1 January 2010 to 31 December 2013 in the area of Midi-Pyrénées (southwest of France). Of the 355,608 patients identified, 325,216 (91.5%) were included, of whom 22,142 received at least one DOAC. About 39.1% (8,652 patients) had DOAC in an orthopedic indication, 46.5% (10,303 patients) in a cardiac indication, and 16.1% (3568 patients) in an indeterminate indication. Overall, guidelines were largely followed as for renal function monitoring, prescribing in orthopedic indications, in cardiac indications in patients aged 80 years and older, and in the case of concomitant use of verapamil. However, inappropriate prescriptions were observed for cardiac indications, and for dosage adjustments in orthopedic indications, with respect to both the age of patients (75 years and older) and those taking verapamil or amiodarone concomitantly. Guidelines were more followed in women and patients aged 80 or more. Among patients receiving DOACs, 58% were exposed to a prescription falling outside the guidelines. This study on DOAC prescription patterns revealed insufficiencies in the compliance with the French guidelines in certain indications.

Non-vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation

DEFF Research Database (Denmark)

Staerk, Laila; Fosbøl, Emil Loldrup; Gadsbøll, Kasper

2016-01-01

Among atrial fibrillation (AF) patients, Danish nationwide registries (2011-2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29...

Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury

NARCIS (Netherlands)

Hofstra, Jorrit J; Vlaar, Alexander P; Cornet, Alexander D; Dixon, Barry; Roelofs, Joris J; Choi, Goda; van der Poll, Tom; Levi, Marcel; Schultz, Marcus J

BACKGROUND: Pulmonary coagulopathy may contribute to an adverse outcome in lung injury. We assessed the effects of local anticoagulant therapy on bronchoalveolar and systemic haemostasis in a rat model of endotoxemia-induced lung injury. METHODS: Male Sprague-Dawley rats were intravenously

Non-Vitamin K antagonist oral anticoagulation usage according to age among patients with atrial fibrillation

DEFF Research Database (Denmark)

Staerk, L.; Fosbøl, E L; Gadsbøll, K.

2016-01-01

Among atrial fibrillation (AF) patients, Danish nationwide registries (2011-2015) were used to examine temporal trends of initiation patterns of oral anticoagulation (OAC) treatment according to age. Overall, 43,299 AF patients initiating vitamin K antagonists (VKA) (42%), dabigatran (29...

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region

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Aníbal García-Sempere

2017-08-01

Full Text Available Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice.Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns.Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%.Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component.

A Multilevel Analysis of Real-World Variations in Oral Anticoagulation Initiation for Atrial Fibrillation in Valencia, a European Region.

Science.gov (United States)

García-Sempere, Aníbal; Bejarano-Quisoboni, Daniel; Librero, Julián; Rodríguez-Bernal, Clara L; Peiró, Salvador; Sanfélix-Gimeno, Gabriel

2017-01-01

Introduction: Beyond clinical trials, clinical practice guidelines, and administrative regulation, treatment decision-making can be influenced by individual and contextual factors. Our goal was to describe variations in the patterns of initiation of anticoagulation therapy in patients with atrial fibrillation by Health Areas (HA) in the region of Valencia in Spain and to quantify the influence of the HAs on variations in treatment choice. Methods: We conducted a population-based retrospective cohort study of all atrial fibrillation patients who started treatment with oral anticoagulants between November 2011 and February 2014 in each of the region's 24 HAs. We described patient and utilization characteristics per HA and initiation patterns over time, and we identified contextual and individual factors associated with differences in initiation patterns. Results: 21,879 patients initiated treatment with an oral anticoagulant in the 24 HAs. Initiation with direct oral anticoagulants (DOAC) in the first year was 14.6%. In November 2013 the ratio was 25.4%, with HA ratios ranging from 3.8 to 57.1%. DOAC-initiating patients had less comorbidity but were more likely to present episodes of previous ischemic stroke, hemorrhagic stroke, or TIA when compared with patients initiating with VKA treatment. Variability among HAs was statistically significant, with the majority of HAs ranking above or below the regional initiation average (ICC ≈ 8%). Conclusion: There was high variability in the percentage of DOAC initiation and in the choice of DOAC among HAs. Interventions aimed to improve DOAC initiation decision-making and to reduce variations should take into account the Health Area component.

Endotoxin dosage in sepsis

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Vincenzo Rondinelli

2012-03-01

Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

Quality of anticoagulation management with warfarin among outpatients in a tertiary hospital in Addis Ababa, Ethiopia: a retrospective cross-sectional study.

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Fenta, Teferi Gedif; Assefa, Tamrat; Alemayehu, Bekele

2017-06-06

Warfarin is the most widely used anticoagulant in the world. The difficulty of managing warfarin contributes to great potential for patient harm, both from excessive anticoagulation and insufficient anticoagulation. This study assessed the International Normalized Ratio (INR) control outcome measures and warfarin dose adjustment practices at cardiology and hematology outpatient clinics at a teaching hospital in Addis Ababa, Ethiopia. The study was based on a cross - sectional study design involving 360 retrospective patients' chart review among outpatients who received warfarin for its various indications. The mean frequency of INR monitoring per patient was 62.9 days (17.2-143.7 days). Patients spent 52.2%, 29.0% and 18.8% of the time in sub-therapeutic, therapeutic and supra-therapeutic ranges, respectively. The daily warfarin dose was increased 50.9% and 36.9% and decreased in 52.8% and 60.9% of the time for occurrences of sub-therapeutic and supra-therapeutic INRs to achieve target ranges of 2.0-3.0 and 2.5-3.5, respectively. The quality of anticoagulation management with warfarin among outpatients in Tikur Anbessa Specialized Hospital was sub-optimal. This was reflected by low Time in Therapeutic Range (TTR), longer than recommended INR monitoring frequency, and minimal actions taken to adjust warfarin dose after occurrences of non-therapeutic INRs.

Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

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Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

2013-12-01

To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

Comparing intracerebral hemorrhages associated with direct oral anticoagulants or warfarin.

Science.gov (United States)

Kurogi, Ryota; Nishimura, Kunihiro; Nakai, Michikazu; Kada, Akiko; Kamitani, Satoru; Nakagawara, Jyoji; Toyoda, Kazunori; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Matsuda, Shinya; Yoshimura, Shinichi; Okuchi, Kazuo; Suzuki, Akifumi; Nakamura, Fumiaki; Onozuka, Daisuke; Ido, Keisuke; Kurogi, Ai; Mukae, Nobutaka; Nishimura, Ataru; Arimura, Koichi; Kitazono, Takanari; Hagihara, Akihito; Iihara, Koji

2018-03-27

This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)-associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database. We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge. DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039). This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

African Journals Online (AJOL)

Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

Fourteen days oral administration of therapeutic dosage of some ...

African Journals Online (AJOL)

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

Optimizing the dosage of stabilizing chemical

OpenAIRE

Harjula, Tomi

2013-01-01

A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

Use of anticoagulant rodenticides in outdoor urban areas: considerations and proposals for the protection of public health and non-target species.

Science.gov (United States)

Dutto, M; Di Domenico, D; Rubbiani, M

2018-01-01

Rodent control operations represent an important tool for the prevention and management of infestations, in outdoor environments, by synanthropic rodents (Rattus rattus and R. norvegicus), which are a source of economic and environmental damage with significant sanitary implications. Although the use of anticoagulants is safer to humans and pets compared to the use of acute poisoning substances, an intrinsic hazard of the active ingredients exists, i.e. the possible poisoning of non-target organisms (e.g., children, pets and wildlife) following exposure. The risks arising from the use of anticoagulants for rodent control operations in anthropic contexts can therefore only be mitigated by a proper selection of the active ingredient, bait formulation and administration techniques, since an active ingredient with selective action towards non-target species does not currently exist on the market. This document lists practical proposals aimed at reducing the possibility of toxic exposure to anticoagulant rodenticides and mitigate the toxicological risk of human baits and non-target species.

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

Science.gov (United States)

Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

2016-08-01

To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

Science.gov (United States)

Overton, Donald A.; Stanwood, Gregg D.; Patel, Bhavesh N.; Pragada, Sreenivasa R.; Gordon, M. Kathleen

2009-01-01

Rationale Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. Objectives Compare three methods for determining the threshold dosage for phenobarbital (D) versus no drug (N) DD. Methods Rats learned a D versus N DD in 2-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last 6 D and 6 N sessions of a block. The criteria were: D%>66 and N%50 and N%33. Two squads of rats were trained, one immediately after the other. Results All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained 2nd may have benefited by partially duplicating the lever choices of the previous squad. Conclusions The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed, and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are permissive, and that allow rats to maintain lever preferences. PMID:19082992

[Post-marketing re-evaluation about usage and dosage of Chinese medicine based on human population pharmacokinetics].

Science.gov (United States)

Jiang, Junjie; Xie, Yanming

2011-10-01

The usage and dosage of Chinese patent medicine are determined by rigorous evaluation which include four clinical trail stages: I, II, III. But the usage and dosage of Chinese patent medicine are lacked re-evaluation after marketing. And this lead to unchanging or fixed of the usage and dosage of Chinese patent medicine instead of different quantity based on different situations in individual patients. The situation of Chinese patent medicine used in clinical application is far away from the idea of the "Treatment based on syndrome differentiation" in traditional Chinese medicine and personalized therapy. Human population pharmacokinetics provides data support to the personalized therapy in clinical application, and achieved the postmarking reevaluating of the usage and dosage of Chinese patent medicine. This paper briefly introduced the present situation, significance and the application of human population pharmacokinetics about re-evaluation of the usage and dosage of Chinese patent medicine after marketing.