Poller, L; Roberts, C; Ibrahim, S;
Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non......-inferiority to the manual dosage at the experienced centers in the EAA study. With the use of a cluster sampling procedure, a minimum number of centers and a minimum total of patients required to establish non-inferiority were determined. At least four centers, each recruiting 50 patients over a period of 6...... months, were shown to be required (excluding the results from the first 3 weeks of treatment). To achieve non-inferiority, the lower 95% confidence interval of the 'time in target International Normalized Ratio range' (TIR) of a marketed program must be above the TIR limit set by the manual dosage group...
Wellman, Jessica C; Kraus, Peggy S; Burton, Bradley L; Ensor, Christopher R; Nesbit, Todd W; Ross, Patricia A; Thomas, Michelle L; Streiff, Michael B
PURPOSE. A stepwise approach to development and implementation of a program to standardize and increase pharmacists' involvement in anticoagulation therapy at a large academic medical center is described. SUMMARY. In response to the Joint Commission's national goal of improved patient safety in anticoagulation therapy, a work group of pharmacy administrators, educators, clinical specialists, and decentralized pharmacists at the hospital developed the structure for a comprehensive inpatient anticoagulation program (IAP); the work group also developed a list of required competencies, educational materials, assessment methods, and mechanisms for eliciting feedback from IAP pharmacists and other patient care staff. After completion of training that included structured case-review sessions, a one-on-one shadowing experience, and competency assessment, IAP pharmacists began reviewing clinical and laboratory data on patients receiving warfarin and low-molecular-weight heparins and providing recommendations to physicians, nurse practitioners, and other health care team members. Feedback from other clinicians was generally positive, with a majority of those surveyed indicating that increased pharmacist involvement in anticoagulation monitoring and dosage adjustment resulted in improved patient care; about 80% indicated that they concurred with pharmacists' recommendations at least 75% of the time. Results of a survey of IAP pharmacists indicated increased satisfaction with their daily duties but also a need for improved pharmacist-to-pharmacist communication. CONCLUSION. Case-based advanced training and implementation of an IAP in a tertiary care hospital increased pharmacists' involvement in the management of inpatients receiving anticoagulants. PMID:21546645
Full Text Available In Japan, low-dose rivaroxaban [15 mg QD/10 mg QD for creatinine clearance of 30-49 mL/min] was approved for clinical use in NVAF patients partly because of its unique pharmacokinetics in Japanese subjects. The aim of the study was to determine the anticoagulation intensity of rivaroxaban and its determinant factors in Japanese stroke patients.Consecutive stroke patients with NVAF admitted between July 2012 and December 2013 were studied. Prothrombin time (PT, activated partial thromboplastin time (aPTT, and estimated plasma concentration of rivaroxaban (Criv based on an anti-factor Xa chromogenic assay were measured just before and 4 and 9 h after administration at the steady state level of rivaroxaban. Determinant factors for Criv were explored using a linear mixed-model approach.Of 110 patients (37 women, 75±9 years old, 59 took 15 mg QD of rivaroxaban and 51 took 10 mg QD. Criv at 4 h was 186 ng/mL for patients taking 15 mg QD and 147 ng/mL for those taking 10 mg QD. Both PT and aPTT were positively correlated with Criv. Criv was 72% lower at 4 h in 15 patients receiving crushed tablets than in the other patients, and tablet crushing was significantly associated with lower Criv (adjusted estimate -0.43, 95% CI -0.60 to -0.26 after multivariate-adjustment.The anticoagulation effects of rivaroxaban in the acute stroke setting for Japanese NVAF patients were relatively low as compared with those in the ROCKET-AF and J-ROCKET AF trials. Tablet crushing, common in dysphagic patients, decreased Criv.
Lluís Cuixart Costa
Full Text Available Introduction. Anticoagulant treatment, despite providing a clear benefit to prevent and treat thrombo-embolic disease, is difficult to manage in routine practice. This is due to individual variability of dosing, narrow therapeutic margin, drug interactions, and side effects. An increasing number of patients admitted to nursing homes are under oral anticoagulant therapy because of deep venous thrombosis and, especially, atrial fibrillation. These are patients with a profile that makes prescription of anticoagulant treatment more difficult - elderly, taking multiple concomitant medications and with multiple ailments. Objetive. We hypothesized that the implementation of a primary care pharmacological follow-up program of oral anticoagulant therapy in patients admitted to nursing homes, with the purpose of coordinating the different professionals and care levels, would lead to greater benefit and reduction of side effects. Methods. A one-year descriptive prospective cohort study was conducted of 27 patients admitted to nursing homes who are under anticoagulation therapy followed by the primary care team. We analyzed different variables obtained from computerized medical records, from which indicators on the program were established (coverage and registration as well as outcome indicators (as defined by the British Committee for Standards in Haematology. Results. The profile of patients under anticoagulation and admitted to nursing homes is elderly (84 years, with a predominance of women (70%, atrial fibrillation as most frequent indication (70.4%, hypertension as major cardiovascular risk factor (92% and most of them on multiple drugs (92%. The analysis of the program results showed excellent coverage and registration indicators (100%. Outcome indicators also showed good results, with percentages of optimal international normalized ratio of 78% (exceeding the defined minimum standard and very low rates of complications (3%. Conclusions. The
Riviere, J E; Frazier, D L; Tippitt, W L
Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data. The program allows the user to specify certain parameters of the dosage regimen, then calculates the other parameters (given desired maximum and minimum serum concentrations, dose and interval are calculated; given desired maximum serum concentration and interval, dose is calculated, etc.). Given the kinetic parameters, the dose and dosing interval, the program calculates and plots the serum concentration-time profile of the drug for that animal. The time and the number of doses to reach steady state can be calculated as well as the determination of loading dose. The percentage of the time of a dosing interval at steady state that the serum concentration is above a specific minimum inhibitory concentration (MIC) allows evaluation of efficacy of an antimicrobial regimen. Similarly, the time to reach a specific concentration (e.g. residue tolerance) or the MIC of a drug can be calculated. Legal tissue tolerances can be accessed from FARAD to aid in predicting for what period of time illegal residues will remain in the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3210265
Bishop, Lisa; Young, Stephanie; Twells, Laurie; Dillon, Carla; Hawboldt, John
Background A pharmacist managed anticoagulation service was initiated in a multi-physician family medicine clinic in December 2006. In order to determine the patient and physician satisfaction with the service, a study was designed to describe the patients’ satisfaction with the warfarin education and management they received from the pharmacist, and to describe the physicians’ satisfaction with the level of care provided by the pharmacist for patients taking warfarin. A self-administered sur...
Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister
Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as 'superwarfarins', 'single dose' or 'long-acting'. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K(1)-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K(1)-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K(1)-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to
Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie
Background Oral anticoagulation therapy is increasingly used for the prevention and treatment of thromboembolic complications in various clinical situations. Nowadays, education programs for patients treated with anticoagulants constitute an integrated component of their management. However, such programs are usually based on the healthcare providers’ perceptions of what patients should know, rather than on patients’ preferences. Objective To investigate patients’ viewpoints on educational needs and preferred modalities of information delivery. Methods We conducted an observational study based on a self-administered questionnaire. To explore several profiles of patients, the study was designed for enrolling patients in two settings: during outpatient consultations in a cardiology department (Saint Antoine Hospital, Paris, France) and in community pharmacies throughout France. Results Of the 371 patients who completed the questionnaire, 187 (50.4%) were recruited during an outpatient consultation and 184 (49.6%) were recruited in community pharmacies. 84.1% of patients were receiving a vitamin K antagonist and 15.6% a direct oral anticoagulant. Patients ranked 16 of 21 (76.2%) questionnaire items on information about their treatment as important or essential; information on adverse effects of treatment was the highest ranked domain (mean score 2.38, 95% CI 2.30–2.46). Pharmacists (1.69, 1.58–1.80), nurses (1.05, 0.95–1.16), and patient associations (0.36, 0.29–0.44), along with group sessions (0.85, 0.75–0.95), the internet (0.77, 0.67–0.88), and delivery of material at the patient’s home (1.26, 1.14–1.38), were ranked poorly in terms of delivering educational material. Conclusion This study revealed substantial discrepancies between patient preferences and current educational programs. These findings should be useful for tailoring future educational programs that are better adapted to patients, with a potential associated enhancement of their
Smokowski, Paul R; Guo, Shenyang; Wu, Qi; Evans, Caroline B R; Cotter, Katie L; Bacallao, Martica
Positive Action (PA) is a school-based intervention for elementary-, middle-, and high-school students that aims to decrease problem behaviors (e.g., violence, substance use) and increase positive behaviors (e.g., academic achievement, school engagement). PA has a long history of documented success achieving these aims, making it an Evidence Based Practice (EBP). Intervention research on EBP's has established the importance of implementation fidelity, especially with regard to program dosage; failure to properly implement an EBP can have negative consequences on targeted outcomes, especially if participants are exposed to a low dosage of the program (e.g., fewer lessons than specified). Much of the current research on PA has neglected to examine how program dosage impacts PA's effect on targeted outcomes. Using propensity score models, multiple imputation, and a 2-level hierarchical linear model, the current study fills this gap and examines how different dosages of PA as measured by years participating in PA and number of PA lessons, impacts adolescent internalizing symptoms, aggression, perceptions of school hassles, and self-esteem over a 3-year period. The current sample included middle school students in grades 6, 7, and 8 (N = 5,894). The findings indicate that students who received 3 years of the PA intervention and a high number of PA lessons had a significantly higher self-esteem score than those who received 0 years of PA or zero lessons. Participants who received 1 year of PA also reported significantly lower school hassle scores than those who received 0 years. Dosage had no statistically significant effects on aggression or internalizing score. Implications are discussed. (PsycINFO Database Record PMID:26950079
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
Ferreira, Joana Lima; Wipf, Joyce E
Anticoagulants are beneficial for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation. The development of target-specific oral anticoagulants is changing the landscape of anticoagulation therapy and created growing interest on this subject. Understanding the pharmacology of different anticoagulants is the first step to adequately treat patients with best available therapy while avoiding serious bleeding complications. This article reviews the pharmacology of the main anticoagulant classes (vitamin K antagonists, direct oral anticoagulants, and heparins) and their clinical indications based on evidence-based data currently available in the literature. PMID:27235611
@@ VTE of the main treatment for anticoagulant thera-py, anticoagulant therapy drug of choice for low molecu-lar weight heparin (LMWH) for the overwhelming major-ity of clinicians agree that long-term oral anticoagulant therapy is still Vit. K antagonist (mainly warfarin).
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.
McMahon, Sean R; Brummel-Ziedins, Kathleen; Schneider, David J
Despite advances in interventional and pharmacologic therapy, survivors of myocardial infarction remain at an increased risk of subsequent cardiovascular events. Initial pharmacological management includes both platelet inhibition and parenteral anticoagulation, whereas long-term pharmacological therapy relies on antiplatelet therapy for prevention of thrombotic complications. Biomarkers showing ongoing thrombin generation after acute coronary syndromes suggest that anticoagulants may provide additional benefit in reducing cardiovascular events. We review the pharmacokinetics of novel anticoagulants, clinical trial results, the role of monitoring, and future directions for the use of novel oral anticoagulants in the treatment of coronary artery disease. Clinical trials have shown that long-term use of oral anticoagulants decreases the risk of cardiovascular events, but they do so at a cost of an increased risk of bleeding. Future studies will need to identify optimal treatment combinations for selected patients and conditions that address both the appropriate combination of therapy and the appropriate dosage of each agent when used in combination. PMID:27228186
Reyes, Maria Regina; Brackett, Marc A.; Rivers, Susan E.; Elbertson, Nicole A.; Salovey, Peter
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…
Lee, C R; Thrasher, K A
The clinical significance of rifampin's induction of warfarin metabolism is well documented, but no published studies or case reports have quantified this interaction with respect to the international normalized ratio (INR). A patient receiving concomitant rifampin and warfarin to treat a mycobacterial infection and intraventricular thrombus, respectively, underwent routine INR testing at a pharmacist-managed anticoagulation clinic to assess his anticoagulation regimen. A 233% increase in warfarin dosage over 4 months proved insufficient to attain a therapeutic INR during long-term rifampin therapy More aggressive titration of the warfarin dosage was needed. In addition, a gradual 70% reduction in warfarin dosage over 4-5 weeks was necessary to maintain a therapeutic INR after rifampin discontinuation, demonstrating the clinically significant offset of this drug interaction. Extensive changes in warfarin dosage are required to attain and maintain a therapeutic INR during the initiation, maintenance, and discontinuation of rifampin. PMID:11601670
Dillon Carla; Twells Laurie; Bishop Lisa; Young Stephanie; Hawboldt John; O'Shea Patrick
Abstract Background The beneficial outcomes of oral anticoagulation therapy are dependent upon achieving and maintaining an optimal INR therapeutic range. There is growing evidence that better outcomes are achieved when anticoagulation is managed by a pharmacist with expertise in anticoagulation management rather than usual care by family physicians. This study compared a pharmacist managed anticoagulation program (PC) to usual physician care (UC) in a family medicine clinic. Methods A retros...
Norton, J L; Gibson, D L
The establishment of a pharmacist-managed out-patient anticoagulation clinic in a private community hospital is described. Discussions by pharmacy with office-based physicians at a 187-bed, private, nonprofit community medical center indicated that the traditional system of anticoagulation management was not ideal for the physicians or their patients. Development of a pharmacist-managed anticoagulation clinic began in fall 1993; operations began in spring 1994. Planning included analyzing existing practices, reviewing the relevant literature, obtaining physician input, visiting an established anticoagulation clinic, formulating a business plan, and developing clinical protocols. Collaborative relationships were established with the hospital laboratory, business office, and risk management, information services, and medical records departments. Two pharmacists were trained to work in the clinic and provide coverage 24 hours a day. Services include patient assessment, monitoring of anticoagulation, warfarin dosage adjustment, medication management, patient education, follow-up care, and providing feedback to referring and attending physicians. The clinic has met with physician and patient satisfaction, has reduced the number of admissions to treat warfarin-related bleeding, and has been able to cover its direct costs. A pharmacist-managed anti-coagulation clinic was successfully established in a private community hospital. PMID:8734675
Howie, P W
Thromboembolic disorders are still a serious problem in pregnancy and anticoagulants have an important part to play in both treatment and prevention. Warfarin is the most convenient drug to give but can cause maternal and fetal bleeding problems, especially during late pregnancy and delivery. There are also small risks of embryopathy from warfarin in early pregnancy but these may have been overstated. Heparin, which has to be given parenterally, does not cross the placental barrier but can still cause bleeding problems in pregnancy. Full intravenous heparin is only suitable for short-term use, and subcutaneous heparin has been introduced for long-term therapy. This regimen is a useful advance but long-term use still has problems of bruising and maternal bone demineralization. The standard treatment of acute thromboembolic events in pregnancy is continuous intravenous heparin followed by either subcutaneous heparin or warfarin, the latter being changed at 36 weeks gestation. In the prophylaxis of thromboembolism, the trend is towards a more selective approach, anticoagulants being given during pregnancy to those at highest risk and during labour and the puerperium to all with a previous history of thromboembolism. Anticoagulants during pregnancy are necessary in patients with artificial heart valves and, because subcutaneous heparin is not sufficient, warfarin should be used until 36 weeks followed by continuous intravenous heparin until delivery. No method of anticoagulation during pregnancy is entirely free of risk and all management policies must be based on an estimate of risk-benefit ratio in individual patients. PMID:2426029
Koopmans, SA; VanRij, G
A questionnaire was sent to 240 members of the Netherlands Intraocular implant Club (NIOIC) to register their policy followed in 1993 with regard to anticoagulant therapy (ACT) and the use of aspirin in patients having cataract surgery. Ninety-one (32%) forms were suitable for analysis. Most eye sur
Steinberg, Benjamin A; Piccini, Jonathan P
Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also available. These novel oral anticoagulants (direct thrombin inhibitors and factor Xa inhibitors) obviate many of warfarin's shortcomings, and they have demonstrated safety and efficacy in large randomized trials of patients with non-valvular atrial fibrillation. However, the management of patients taking warfarin or novel agents remains a clinical challenge. There are several important considerations when selecting anticoagulant therapy for patients with atrial fibrillation. This review will discuss the rationale for anticoagulation in patients with atrial fibrillation; risk stratification for treatment; available agents; the appropriate implementation of these agents; and additional, specific clinical considerations for treatment. PMID:24733535
Garabedian-Ruffalo, S M; Gray, D R; Sax, M J; Ruffalo, R L
The effectiveness of a pharmacist-managed warfarin anticoagulation clinic in maintaining therapeutic prothrombin times and preventing hospitalizations secondary to inadequate control of anticoagulation was evaluated. Patients who had received warfarin sodium for at least one year before being referred to the anticoagulation clinic were studied using retrospective chart reviews. Clinical pharmacists provided patient education, monitored patients for hemorrhagic and thromboembolic complications, and adjusted warfarin sodium dosage to maintain therapeutic prothrombin times. The patients' primary physicians retained responsibility for overall care and were consulted by pharmacists regarding complications of anticoagulation and patient unreliability. The percentage of patients requiring hospitalization (39% versus 4%) and the percentage of prothrombin times outside the therapeutic range (35.8% versus 14.4%) were significantly higher during the preclinic phase (before referral to the clinic) than during the clinic phase. Eight patients were hospitalized for hemorrhagic complications and four for thromboembolism during the preclinic phase; only one hospitalization for hemorrhage occurred during the clinic phase. The warfarin anticoagulation clinic staffed by specially trained pharmacists provided improved therapy compared with treatment received by patients before their referral to the clinic. PMID:3976675
Ahmad, Yousif; YH Lip, Gregory
Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This...
Steinberg, Benjamin A; Piccini, Jonathan P.
Atrial fibrillation increases the risk of stroke, which is a leading cause of death and disability worldwide. The use of oral anticoagulation in patients with atrial fibrillation at moderate or high risk of stroke, estimated by established criteria, improves outcomes. However, to ensure that the benefits exceed the risks of bleeding, appropriate patient selection is essential. Vitamin K antagonism has been the mainstay of treatment; however, newer drugs with novel mechanisms are also availabl...
De Lange, J J; Van Kleef, J W; Van Everdingen, J J E
In a patient with a coagulation disorder, the administration of a local anaesthetic by means of a needle or via the insertion of a catheter into the epidural space or spinal cavity may lead to bleeding and haematoma formation, with a danger of pressure on the spinal cord or nerve roots. Employing the method of the Dutch Institute for Healthcare (CBO) for the development of practice guidelines, a working group of anaesthesiologists, a haematologist and a hospital chemist have drawn up recommendations for neuraxis blockade in combination with anticoagulant therapy. In patients with a clinically acquired tendency toward increased bleeding, the management is highly dependent on the cause of the bleeding tendency. If the patient uses acetylsalicylic acid or clopidogrel, the medication must be withdrawn at least 10 days before neuraxis blockade is started. Therapy with glycoprotein-IIb/IIIa-receptor antagonists is an absolute contra-indication for neuraxis blockade. In patients who are using coumarin derivatives, neuraxis blockade results in an increased risk of a neuraxial haematoma. The coumarin derivative should then be withdrawn and replaced by a different form of anticoagulation. The use of low-molecular-weight heparin at the usual prophylactic dosage is not a contra-indication for neuraxis blockade and the risk of a neuraxial haematoma following neuraxis blockade is also not increased significantly by the subcutaneous administration of unfractionated heparin. PMID:15366721
Wooten, James M
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. PMID:23211502
Low leukocyte count secondary to leukocyte aggregation caused by an ethylene diamine tetra acetic acid (EDTA) occur in both benign and malignant disorders. We report a 71-year-old male patient who was admitted to the hospital with acute chest infection. Complete blood count (CBC) collected in ETDA tube and analyzed by sysmex instrument (SE/9500) revealed low hemoglobin level of 9.4g/dl, white blood cell (WBC) count of 8.2x109/L. Peripheral blood smear review shows multiple leukocyte aggregation (one clump in each field). When we asked for another blood sample in citrate anticoagulant, the CBC showed WBC count of 11.8x109/L and neutrophils of 6.26x109/L. This is a case of low leukocyte count secondary to leukocyte aggregation induced by EDTA. (author)
Pengo, Vittorio; Pegoraro, Cinzia; Cucchini, Umberto; Iliceto, Sabino
A multicenter, observational, retrospective, cross-sectional study of patients, receiving oral anticoagulation therapy (OAT) for stroke prophylaxis in chronic non-valvular atrial fibrillation (NVAF) was conducted in the US, Canada, France, Italy and Spain according to their predominant model of care [routine medical care (RMC) or Anticoagulation Clinic care (ACC)]. The study objectives were to assess anticoagulation control (time in target range), and to describe the features of the local model of care. Consecutive patients were recruited on the basis of a minimum of 60 days of oral anticoagulant treatment over a 12 month period, and clinic and physician details were captured by means of a structured face-to-face or telephone interview. Time in therapeutic range (TTR) was calculated by using linear interpolation between INR values. A total of 1511 patients were recruited, of whom 1445 were included in the analysis of TTR. TTR was higher in ACC (69.5% and 64.9% for Italy and Spain, respectively) with respect to RMC (58.1%, 62.8% and 59.3% for the US, Canada and France, respectively). Mean intervals between INR determinations were between 3 and 4 weeks. Dose changes in case of INR outside therapeutic range were more frequent in Spain and less frequent in France. Striking differences were observed in type of VKA used, specialists involved in patient management, and dosage instructions. Studying of anticoagulation management based on local models of care highlights important discrepancies among countries and suggests further standardization of the management of this important therapy is necessary. PMID:16475046
DeLoughery, Thomas G
DeLoughery, Thomas G. Anticoagulation considerations for travel to high altitude. High Alt Med Biol 16:181-185, 2015.-An increasing percentage of the population are on anticoagulation medicine for clinical reasons ranging from stroke prevention in atrial fibrillation to long term prevention of deep venous thrombosis. In recent years, several new direct oral anticoagulants have entered the market. The key questions that should be kept in mind when approaching a potential traveler on anticoagulation are: 1) why is the patient on anticoagulation? 2) do they need to stay on anticoagulation? 3) what are the choices for their anticoagulation? 4) will there be any drug interactions with medications needed for travel? and 5) how will they monitor their anticoagulation while traveling? Knowing the answers to these questions then can allow for proper counseling and planning for the anticoagulated traveler's trip. PMID:26186419
Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B
Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH. PMID:27137522
Parks, Anna L; Fang, Margaret C
The number of patients with atrial fibrillation (AF) who are of advanced age or have multiple comorbidities is expected to increase substantially. Older patients with AF generally gain a net benefit from anticoagulation. Guidelines typically recommend anticoagulation. There are multiple challenges in the safe use of anticoagulation in frail patients, including bleeding risk, monitoring and adherence, and polypharmacy. Although there are options for chronic oral anticoagulation, clinicians must understand the unique advantages and disadvantages of these medications when developing a management plan. This article reviews issues surrounding the appropriate use and selection of anticoagulants in complex older patients with AF. PMID:27113150
Full Text Available Amber L Beitelshees,1,* Deepak Voora,2,* Joshua P Lewis,1,* 1Program for Personalized and Genomic Medicine and Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA; 2Center for Applied Genomics & Precision Medicine, Department of Medicine, Duke School of Medicine, Durham, NC, USA*All authors contributed equally to this work Abstract: In recent years, substantial effort has been made to better understand the influence of genetic factors on the efficacy and safety of numerous medications. These investigations suggest that the use of pharmacogenetic data to inform physician decision-making has great potential to enhance patient care by reducing on-treatment clinical events, adverse drug reactions, and health care-related costs. In fact, integration of such information into the clinical setting may be particularly applicable for antiplatelet and anticoagulation therapeutics, given the increasing body of evidence implicating genetic variation in variable drug response. In this review, we summarize currently available pharmacogenetic information for the most commonly used antiplatelet (ie, clopidogrel and aspirin and anticoagulation (ie, warfarin medications. Furthermore, we highlight the currently known role of genetic variability in response to next-generation antiplatelet (prasugrel and ticagrelor and anticoagulant (dabigatran agents. While compelling evidence suggests that genetic variants are important determinants of antiplatelet and anticoagulation therapy response, significant barriers to clinical implementation of pharmacogenetic testing exist and are described herein. In addition, we briefly discuss development of new diagnostic targets and therapeutic strategies as well as implications for enhanced patient care. In conclusion, pharmacogenetic testing can provide important information to assist clinicians with prescribing the most personalized and effective antiplatelet and
Radley, A S; Hall, J; Farrow, M.; Carey, P J
AIMS--To compare the quality of outpatient anticoagulant control before and after the transfer of dosing responsibility to designated trained pharmacists from rotating junior medical staff. METHODS--All International Normalised Ratio (INR) values for an eight month period either side of the staff changeover were assessed for precision of therapeutic control according to described standards. Allowing for patient associated effects, observed and expected frequencies of "successful" control for ...
Chighizola, Cecilia Beatrice; Raschi, Elena; Banzato, Alessandra; Borghi, Maria Orietta; Pengo, Vittorio; Meroni, Pier Luigi
The term "lupus anticoagulant" (LA) refers to a heterogeneous group of immunoglobulins behaving as acquired in vitro inhibitors of coagulation. These antibodies, namely anti-β2GPI and anti-prothrombin antibodies, induce the in vitro elongation of clotting time interfering with phospholipid-dependent coagulation cofactors. Positive LA is associated with thrombosis and pregnancy complications, providing one of the three laboratory criteria for the classification of the anti-phospholipid syndrome. LA is the strongest predictor of clinical events, especially when associated with other anti-phospholipid antibodies. Much more controversial is the risk conveyed by isolated and weak LA. LA detection is technically laborious, envisaging screening, mixing and confirming tests. Hopefully critical issues in LA detection, such as the interference of anticoagulants, will be overcome, in the next future. PMID:26789237
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.
Valeska Subiabre, MsCs; Ivan Palomo, PhD; Neftalí Guzmán, PhD; Eduardo Retamales, MsCs; Hugo Henríquez, MsCs; Luis Gonzalez, MsCs
Background: Vitamin K antagonists are drugs that are widely prescribed around the world and their use has helped improve the prognosis of patients with thromboembolic disease. However, a high interindividual variability has been observed in dosage requirements to reach the desired anticoagulation range that could be due to environmental and genetic factors. Studies suggest that ethnicity influences coumarin response, supporting the observed differences in dose requirements across various popu...
Mehlberg, J; Wittkowsky, A K; Possidente, C
A national survey of pharmacist-managed anticoagulation clinics was conducted to determine how pharmacists are trained to provide care in such clinics. In June 1996 a survey was mailed to 177 pharmacist-managed anticoagulation clinics in the United States. A total of 128 surveys were returned (response rate, 72%). One hundred ten surveys representing 42 states and a variety of institutions were usable. Twenty-five (23%) of the 110 clinics offered an anticoagulation training program for their pharmacists. Most training programs had both didactic and experiential components and had been in existence for one to five years. Thirty-two (29%) of the 110 responding clinics had at least one pharmacist who had completed the ASHP Research and Education Foundation's Anticoagulation Service Traineeship. Twenty-three of the 25 clinics with a training program required successful completion of the program before a pharmacist could practice in the clinic. The overall quality of pharmacists' performance was regularly assessed by 22 of the 25 clinics. Most pharmacist-managed anticoagulation clinics in the United States do not offer formal training in anticoagulation therapy to pharmacists who practice in that setting. PMID:9606455
... AerobiKa® Cardiology Medications Anticoagulant Medicine Anticoagulants and Drug-Food Interactions COPD Medications Bronchodilators Anti-Inflammatories Antibiotics Managing Your Medications Devices ...
Lin, Tao; Bai, Rong; Chen, Ying-wei; Yu, Rong-hui; Tang, Ri-bo; Sang, Cai-hua; Li, Song-nan; Ma, Chang-sheng; Dong, Jian-zeng
Anticoagulation of patients with cardiac tamponade (CT) complicating catheter ablation of atrial fibrillation (AF) is an ongoing problem. The aim of this study was to survey the clinical practice of periprocedural anticoagulation in such patients. This study analyzed the periprocedural anticoagulation of 17 patients with CT complicating AF ablation. Emergent pericardiocentesis was performed once CT was confirmed. The mean drained volume was 410.0 ± 194.1 mL. Protamine sulfate was administered to neutralize heparin (1 mg neutralizes 100 units heparin) in 11 patients with persistent pericardial bleeding and vitamin K1 (10 mg) was given to reverse warfarin in 3 patients with supratherapeutic INR (INR > 2.1). Drainage catheters were removed 12 hours after echocardiography confirmed absence of intrapericardial bleeding and anticoagulation therapy was restored 12 hours after removing the catheter. Fifteen patients took oral warfarin and 10 of them were given subcutaneous injection of LMWH (1 mg/kg, twice daily) as a bridge to resumption of systemic anticoagulation with warfarin. Two patients with a small amount of persistent pericardial effusion were given LMWH on days 5 and 13, and warfarin on days 6 and 24. The dosage of warfarin was adjusted to keep the INR within 2-3 in all patients. After 12 months of follow-up, all patients had no neurological events and no occurrence of delayed CT. The results showed that it was effective and safe to resume anticoagulation therapy 12 hours after removal of the drainage catheter. This may help to prevent thromboembolic events following catheter ablation of AF. PMID:25503659
Graham, S P
The current published literature does not indicate whether the long-term effect of anticoagulant or antiplatelet therapy contributes to mortality reduction in patients with LV dysfunction. Evaluating patients for personal risk for emboli or for ischemic coronary artery events may influence the choice of therapies. As more is learned about the mechanisms of drug effects in different populations, physicians may be better able to direct appropriate therapies. Until that time, one must weigh the risks and benefits of each drug alone and in combination. In NYHA class IV patients, the risk for thrombosis owing to spontaneous clotting increases as does the adverse potential of warfarin and the adverse effects of inhibiting prostaglandin mediated vasodilation by aspirin. In NYHA class I and II patients, the quality of life and convenience of multidrug therapy is weighed against the devastating effect of a major stroke. In less symptomatic patients, the long-term risk for acute coronary events may be higher than previously identified. This would suggest that all patients with depressed LV function should be on some type of antiplatelet or anticoagulant therapy. The current WATCH study will provide much needed information about the outcome differences between these agents. Conclusions based on available data include the following: Heart failure is increasing in incidence and prevalence. Atherosclerotic disease is an important causative factor for the development of heart failure or may be a comorbid condition in these patients. There is a measurable rate of stroke in patients with heart failure, although the cause of death in large studies is more often owing to sudden death or progressive heart failure. Sudden death may be from new ischemic events, asystole, or from ventricular tachyarrhythmias. In patients with heart failure, not all strokes are cardioembolic in origin. The benefits and risks of warfarin may be increased as the EF worsens or heart failure functional class
... even if it is not listed below. Aspirin Acetaminophen (e.g., Tylenol, Excedrin) Ibuprofen (e.g., Motrin, ... skin or eyes (jaundice) Rare side effects: Headache Dizziness Shortness of breath Mouth sores or bleeding gums ...
Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.
Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.
Godier, A; Martin, A-C; Rosencher, N; Susen, S
Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development. Other options include hemodialysis for the treatment of dabigatran-associated bleeding and administration of oral charcoal if recent DOAC ingestion. DOAC plasma concentration measurement is necessary to guide DOAC reversal. We propose an update on DOAC-associated bleeding, integrating the availability of dabigatran antidote and the critical place of DOAC concentration measurements. PMID:27297642
Meyer, Barbara J
In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the
Vigano D'Angelo, S; Comp, P C; Esmon, C T; D'Angelo, A.
Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. ...
Full Text Available Abstract Background The beneficial outcomes of oral anticoagulation therapy are dependent upon achieving and maintaining an optimal INR therapeutic range. There is growing evidence that better outcomes are achieved when anticoagulation is managed by a pharmacist with expertise in anticoagulation management rather than usual care by family physicians. This study compared a pharmacist managed anticoagulation program (PC to usual physician care (UC in a family medicine clinic. Methods A retrospective cohort study was carried out in a family medicine clinic which included a clinical pharmacist. In 2006, the pharmacist assumed anticoagulation management. For a 17-month period, the PC group (n = 112 of patients on warfarin were compared to the UC patients (n = 81 for a similar period prior to 2006. The primary outcome was the percentage of time patients' INR was in the therapeutic range (TTR. Secondary outcomes were the percentage of time in therapeutic range within ± 0.3 units of the recommended range (expanded TTR and percentage of time the INR was >5.0 or Results The baseline characteristics were similar between the groups. Fifty-five percent of the PC group was male with a mean age of 67 years; 51% of the UC group was male with a mean age of 71 years. The most common indications for warfarin in both groups were atrial fibrillation, mechanical heart valves and deep vein thrombosis. The TTR was 73% for PC and 65% for UC (p 5 were 0.3% for PC patients and 0.1% for UC (p Conclusion The pharmacist-managed anticoagulation program within a family practice clinic compared to usual care by the physicians achieved significantly better INR control as measured by the percentage of time patients' INR values were kept in both the therapeutic and expanded range. Based on the results of this study, a collaborative family practice clinic using pharmacists and physicians may be an effective model for anticoagulation management with these results verified in future
E.A. Akl; S. Gunukula; M. Barba; V.E.D. Yosuico; F.F. van Doormaal; S. Kuipers; S. Middeldorp; H.O. Dickinson; A. Bryant; H. Schuenemann
Background Anticoagulation may improve survival in patients with cancer through an antitumor effect in addition to the perceived antithrombotic effect. Objectives To evaluate the efficacy and safety of parenteral anticoagulants in patients with cancer with no therapeutic or prophylactic indication f
DU Xin; MA Chang-sheng; LIU Xiao-hui; DONG Jian-zeng; WANG Jun-nan; CHENG Xiao-jing
@@ Nonvalvular atrial fibrillation (NVAF) is the most common sustained cardiac arrhythmia in clinical practice, which if untreated results in a doubling of cardiovascular morbidity and mortality. AF is an independent predictor of stroke, with an annual risk 5 to 6 times higher than patients in sinus rhythm.1 During recent years, several randomised clinical trials conducted by investigators around the world involving 13 843 participants with NVAF have demonstrated convincingly the value of warfarin therapies for stroke prevention in high risk patients.2-8 However, the dose response of warfarin is complex and its activity is easily altered by concurrent medications, food interactions, alcohol and illnesses. Adherence to medical advice and routine monitoring of the international normalized ratio (INR) is important, because low anticoagulant intensity predisposes the patients to thromboembolic complications and high intensity to haemorrhage. Studies suggested that anticoagulant clinics could improve the quality of anticoagulation control,9 and anticoagulant clinics are common in western countries. However, in China, most AF patients taking warfarin usually attend the outpatient clinic of cardiology, while the quality of anticoagulation control is never investigated. We therefore assessed anticoagulation control in the outpatient clinic of cardiology, and the quality of anticoagulation control since the establishment of anticoagulant clinics.
Sudarshan B. Aher; Dattatraya M. Shinkar; Ravindra B. Saudagar
In the drug development enhancement of oral bioavailability of poorly water soluble drugs is one of the most challenging aspects of drug. The pharmaceutical industry face the problem poor dissolution characteristics of water insoluble drug. these problem solve by applying recent techniques “powdered solution technology” or “liquisolid technology”, for prepare water-insoluble drugs into rapid-release solid dosage forms. Design and formulation of this approach is prescribed according to new mat...
Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton;
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....
Yates, Scott W
No agents are approved to reverse the effects of newer anticoagulants used to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. This review focuses on ways to monitor, interrupt, and reverse such anticoagulation.
The prevalence of medical conditions representing a risk for thromboembolic complications and requiring antithrombotic therapy increases gradually with age. Two cases of fatal noncritical organ bleeding complication that occurred during the conversion period from initial fondaparinux to vitamin K antagonist are presented. An 81-year-old obese female patient (body mass index 43 kg/m(2)) with previous postoperative thrombosis underwent uneventful total knee replacement under spinal anesthesia. She presented with popliteal hematoma during conversion to oral anticoagulant. A 92-year-old female patient (body mass index 33 kg/m(2)) with left lower limb thrombosis was referred to our orthopedics department from her senior citizens' home for right lower limb hematoma and ischemia that occurred during conversion to oral anticoagulant. Thromboembolic and bleeding events in the elderly are real public health problems. Specific guidelines dedicated to this particular population are needed, which will improve the management of anticoagulation and decrease risk of complications. PMID:26547115
Nutescu, Edith A.; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann
Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. Thi...
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
Samuel P. Hammar
Full Text Available We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban.
Samamaa, M-M; Conard, J; Flaujac, C; Combe, S; Horellou, M-H
Amongst numerous promising anticoagulant molecules, rivaroxaban (Xarelto(®)), dabigatran (Pradaxa(®)) and apixaban (Eliquis(®)) have been registered outside the USA in the prevention of thromboembolic events in patients undergoing total hip or knee prosthetic replacement. Rivaroxaban however has been granted authorisation by the FDA for the thromboprophylaxis after surgery for total hip or knee surgery. Dabigatran has been granted authorisation by the FDA in non-valvular atrial fibrillation (RE-LY trial) while rivaroxaban is expecting approval in this same indication (ROCKET trial). Phase III results in the treatment and in the secondary prevention of established venous thrombosis and pulmonary embolism are encouraging. These small molecules are obtained by chemical synthesis, their molecular weight is lower than 500 daltons. Many coagulation tests may be affected by these molecules. Those modifications should be known in order to avoid misinterpretation of the tests but could also be used to measure plasma concentrations of these products. The choice of a non specific global and readily available test has been documented (Quick time for rivaroxaban and aPTT for dabigatran). Anti-Xa (for rivaroxaban) and anti-IIa (for dabigatran) activities should however be preferred, expressed in ng/ml with calibrated plasmas (containing predetermined concentration of the tested drug). The half-life is around 8 to 12 hours, with a peak activity 2 to 4 hours after ingestion. Dabigatran is mainly eliminated via the kidney, hence requiring dose-adjustment in case of moderate renal insufficiency, and contra-indicated in case of severe renal insufficiency. Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. No data are available in pregnancy or pediatrics, clinical trials are ongoing. There are few interactions with concomitant drugs, which should not be ignored. The short half-life of these new agents compensates for the
Sudarshan B. Aher
Full Text Available In the drug development enhancement of oral bioavailability of poorly water soluble drugs is one of the most challenging aspects of drug. The pharmaceutical industry face the problem poor dissolution characteristics of water insoluble drug. these problem solve by applying recent techniques “powdered solution technology” or “liquisolid technology”, for prepare water-insoluble drugs into rapid-release solid dosage forms. Design and formulation of this approach is prescribed according to new mathematical model given by spires et al. the solubility is Increasing by using a non-volatile solvent which is suitable for drug, their by dissolving the drug in the non volatile solvent it is termed as liquid medicament. This case, the drug is in a solid dosage form, it is held within the powder substrate in solution or, in a solubilized, almost dispersed state, which contributes to the enhanced drug dissolution and release properties. Liquisolid system is characterized by flow behavior, wettability, powder bed hydrophilicity, saturation solubility, drug content, differential scanning calorimetry, Fourier transform infra red spectroscopy, powder x-ray diffraction, scanning electron microscopy, in-vitro release and in-vivo evaluation.
Nutescu, Edith A; Burnett, Allison; Fanikos, John; Spinler, Sarah; Wittkowsky, Ann
Anticoagulant drugs are the foundation of therapy for patients with VTE. While effective therapeutic agents, anticoagulants can also result in hemorrhage and other side effects. Thus, anticoagulant therapy selection should be guided by the risks, benefits and pharmacologic characteristics of each agent for each patient. Safe use of anticoagulants requires not only an in-depth knowledge of their pharmacologic properties but also a comprehensive approach to patient management and education. This paper will summarize the key pharmacologic properties of the anticoagulant agents used in the treatment of patients with VTE. PMID:26780737
Mukhopadhyay, Suman; Frias, Maria A; Chatterjee, Amrita; Yellen, Paige; Foster, David A
The mTOR pathway is a critical regulator of cell growth, proliferation, metabolism, and survival. Dysregulation of mTOR signaling has been observed in most cancers and, thus, the mTOR pathway has been extensively studied for therapeutic intervention. Rapamycin is a natural product that inhibits mTOR with high specificity. However, its efficacy varies by dose in several contexts. First, different doses of rapamycin are needed to suppress mTOR in different cell lines; second, different doses of rapamycin are needed to suppress the phosphorylation of different mTOR substrates; and third, there is a differential sensitivity of the two mTOR complexes mTORC1 and mTORC2 to rapamycin. Intriguingly, the enigmatic properties of rapamycin dosage can be explained in large part by the competition between rapamycin and phosphatidic acid (PA) for mTOR. Rapamycin and PA have opposite effects on mTOR whereby rapamycin destabilizes and PA stabilizes both mTOR complexes. In this review, we discuss the properties of rapamycin dosage in the context of anticancer therapeutics. Mol Cancer Ther; 15(3); 347-53. ©2016 AACR. PMID:26916116
Barrios, Annette C; Ventura, Hector O; Milani, Richard V
Clinical privileging of pharmacists and the effective use of support staff and information technology have helped create an efficient pharmacist-operated anticoagulation clinic at Ochsner Clinic Foundation that will support future growth efforts for improved patient care. Developed by Ochsner's Department of Cardiology, the pharmacist-operated anticoagulation clinic cares for 2000 patients with a clinical pharmacist, staff pharmacist, registered nurse, and medical assistants. Patients are managed by face-to-face and telephone encounters. The pharmacists are privileged by medical staff to write prescriptions for warfarin, adjust warfarin doses, and conduct appropriate laboratory monitoring. Patients attend a mandatory initial visit where they are given medication instructions and educational materials. The pharmacist determines the treatment dose and schedules follow-up appointments. A software system developed by Ochsner's Information Services Department imports patient data from the institution's central computer system, allowing for a limited electronic patient record. Once fully implemented, this program will allow for more specific patient tracking and assist with quality improvement efforts. At present, approximately 68% of our patient population is within therapeutic range. PMID:22822313
Full Text Available OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Satger, Bernadette; Blaise, Sophie; Fontaine, Michèle; Yver, Jacqueline; Allenet, Benoît; Baudrant, Magali; Pernod, Gilles; Bosson, Jean-Luc
The vitamin K antagonists (VKA) remain to this day the only oral form of therapeutic anticoagulation. Approximately 1% of the French population, mainly elderly, is treated with these anticoagulants. Oral anticoagulants have significant risks of iatrogenic complications; indeed they are the leading cause of such drug-induced complications, predominantly hemorrhages. AFSSAPS (French Drug and Medical Products Agency) clinical practice recommendations, repeatedly disseminated, emphasize the education of patients receiving VKAs. Managing oral anticoagulant treatment is challenging, with a significant risk of under- or overdosing and consequently, thrombosis or hemorrhage. The therapeutic window is narrow, multiple drug-interactions are possible, and the specific dose required for a particular individual to achieve appropriate International Normalized Ratio (INR) levels is unpredictable. The literature contains few randomized controlled trials about the efficacy of education for patients treated with oral anticoagulants. These education programs are not standardized and are therefore varied and difficult to compare. Nevertheless, studies demonstrate the importance of patient education programs in reducing the risk of hemorrhage and achieving better treatment stability. The Grenoble region hospital-community network for vascular diseases (GRANTED) has developed an education program for these patients, consisting of individual sessions for the patient and/or a friend or family member (either at a health care facility or at the patient's home), telephone support and group sessions, and using educational tools and supports. There is also a link with the general practitioner who receives a report. This approach makes it possible to adapt the educational message to individual patients and their daily lives, as well as directly involving them in the management of their treatment. PMID:19815369
Jensen, A S; Idorn, L; Nørager, B;
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. It is....... 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...... 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...
Court, E L
The pathogenesis of the lupus anticoagulant (LA) has been the focus of much research over the past decade, and a plethora of laboratory tests have been developed to detect it. This essay reviews the nature of LA and its pathogenesis, and a number of approaches employed in its diagnosis. These range from well established tests such as the kaolin clotting time (KCT), activated partial thromboplastin time (APTT) and tissue thromboplastin inhibition test (TTI), to the 'newer' tests such as the dilute Russell's viper venom time (DRVVT) and more recent snake venom tests such as the textarin/ecarin ratio and Taipan snake venom time (TSVT). The criteria for diagnosis are discussed, including pre-analytical variables such as sample preparation, and the effects of therapeutic anticoagulants used to treat thrombotic manifestations of the syndrome or an underlying disease process. PMID:9624740
Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L
In an attempt to minimize the economic impact due to the incorporation of innovative drugs, health authorities have promoted and supported the evaluation and market positioning of drugs, as equivalent therapeutic alternatives. This issue has recently gained importance, possibly due to the current economic crisis. The equivalent therapeutic alternatives are justified by the need to compete on price, and by the authorities recommendation to establish therapeutic equivalence, price and financing of medicinal products at the same time. The establishment of the new oral anticoagulants and the equivalent therapeutic alternatives is a problematic issue if it is based on the absence of direct comparisons between different drugs and the questionable methodology used in the current indirect comparisons. Currently, it is difficult to determine when a new oral anticoagulant is more recommendable than others, but efforts are being made in order to propose alternatives for the decision based on patient characteristics. PMID:26146035
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.
Kaczorowska, Beata; Pawełczyk, Małgorzata; Przybyła, Monika
Brain stroke is a grave society problem. About 20% ischemic strokes are cardiac related problems. Atrial fibrillation (AF) is the most common cause of ischemic strokes. Decision to deploy anticoagulant treatment with AF patient depends on bleeding and thrombo-embolic risk which summerise scale CHA2DS2VASc and HAS-BLED. Past recent years in AF treatment anticoagulants from the group of vitamin K antagonist were used. At present in brain stroke prevention and systemic emboilment, new oral anticoagulants (NOA) which weren't worst than vitamin K antagonists, and they are recomendet in most cases of AF unrelated with heart valve defets. Useing NOA causes lower risk of bleeding, including intracranial heamorrhage. It is believed that this is related to the selective inhibition of specific coagulation factors, and respect other hemostatic mechanisms. Results from clinical studies NOA are encouraging, but still lacks clear answers regarding, among other things: long-term safety of treatment and economically viable in everyday clinical practice. In addition, to date there is no specific antidote for this group of drugs. PMID:27234866
Munson, C F; Reid, A J
Novel oral anticoagulants (NOACs) have emerged as a good alternative to warfarin in the prevention of stroke for patients with atrial fibrillation. NOAC use is increasing rapidly; therefore, greater understanding of their use in the perioperative period is important for optimal care. Studies and reviews that reported on the use of NOACs were identified, with particular focus on the perioperative period. PubMed was searched for relevant articles published between January 2000 and August 2015. The inevitable rise in the use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™), edoxaban (Lixiana™) and dabigatran (Pradaxa™) may present a simplified approach to perioperative anticoagulant management due to fewer drug interactions, rapidity of onset of action and relatively short half-lives. Coagulation status, however, cannot reliably be monitored and no antidotes are currently available. When planning for discontinuation of NOACs, special consideration of renal function is required. Advice regarding the management of bleeding complications is provided for consideration in emergency surgery. In extreme circumstances, haemodialysis may be considered for bleeding with the use of dabigatran. NOACs will increasingly affect operative planning in plastic surgery. In order to reduce the incidence of complications associated with anticoagulation, the management of NOACs in the perioperative period requires knowledge of the time of last dose, renal function and the bleeding risk of the planned procedure. Consideration of these factors will allow appropriate interpretation of the current guidelines. PMID:27013144
Olesen, Jonas Bjerring; Sørensen, Rikke; Hansen, Morten Lock;
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...... the drug came on market. By October, 2013, 40% were being started on warfarin and dabigatran, respectively, and another 20% were started on either rivaroxaban or apixaban. Rivaroxaban and apixaban users generally had a higher predicted risk of stroke and bleeding compared with warfarin and dabigatran users....... Older age, female gender, and prior stroke were some of the factors associated with NOAC use vs. warfarin, whereas chronic kidney disease, myocardial infarction, and heart failure showed the opposite association. CONCLUSION: Among oral anticoagulation-naïve AF patients initiated on oral anticoagulation...
Bouwmeester, Carla; Chim, Christine
Pharmacists are at the forefront when caring for patients requiring anticoagulation resulting from chronic conditions, complex medications therapy, or at risk for drug interactions. As a consequence, there is a greater need for pharmacist-managed anticoagulation clinics in the community setting. This article will review special considerations for oral anticoagulant therapy in the elderly, collaborative therapy management, establishment of policies and procedures, documentation of patient visits, patient counseling, and barriers to successful anticoagulation management. It will also discuss evidence-based guidelines for the use of oral anticoagulants and compare the agents currently approved by the Food and Drug Administration. Finally, barriers to anticoagulation management will be examined, including issues with adherence and communication with patients and health care providers. PMID:23649677
Harper, Paul; Harper, Joe; Hill, Claire
Objective To evaluate the effectiveness of a computerised self-adjusting anticoagulant algorithm to predict appropriate warfarin dosing and to assess its use in clinical practice. Design A 3-year audit of anticoagulant control in patients managed by doctors and pharmacists using computer decision support and an evaluation of the impact of dose adjustments made by the users. Participants 3660 patients on oral anticoagulants; one-third of patients managed by doctors and two-thirds by pharmacists. Setting Anticoagulant supervision in primary care and pharmacies at 60 sites in New Zealand. Main outcome measures The time in the therapeutic range (TTR), the outcome of adherence to the computer dosing algorithm, the percentage of time the clinicians over-ride the algorithm and the impact of their intervention on anticoagulant control. Results A TTR of 72.9% was achieved for all patients. The TTR was significantly better in patients managed by pharmacists than doctors (75.1% versus 67.4%, ppharmacists. Conclusions The clinicians predominantly change the dose when the INR is below the therapeutic range. The changes are not necessary to correct for inaccuracies in the algorithm. The most likely explanation is the clinician's belief that their own dose adjustment would achieve better control; however, in practice, their changes tend to underdose patients. The doctors achieved poorer control than the pharmacists; this is in part due to the action of the doctors over-riding the algorithm. Our results imply that clinicians could achieve better anticoagulant control if they more closely followed the computer algorithm. PMID:25183709
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
Cecilia Becattini, Alessandra Lignani, Giancarlo AgnelliInternal and Cardiovascular Medicine and Stroke Unit, University of Perugia, ItalyAbstract: Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal...
Robinson, Austin A.; Ikuta, Kevin; Soverow, Jonathan
Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circums...
Hookworms of the genus Ancylostoma secrete an anticoagulant that both inhibits the clotting of human plasma and promotes fibrin clot dissolution. This anticoagulant activity is attributable to a 36,000 dalton proteolytic enzyme. The protease can degrade fibrinogen into five smaller polypeptides that intrinsically have anticoagulating properties, covert plasminogen to a mini-plasminogen-like molecule, and hydrolyze a synthetic peptide substrate with specificity for elastolytic enzymes. It is h...
Rybak, Iwona; Ehle, Michael; Buckley, Leo; Fanikos, John
Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer major advantages over existing agents. The onset of the anticoagulant effect of these agents is rapid. Each agent has a predictable anticoagulant response that eliminates the need for monitoring. Clinical trials have been completed with all three agents in the prevention and treatment of the three leading causes of cardiovascular death: myocardial infarction, stroke, and venous thromboembolism (VTE). Novel agents h...
Witt, Daniel M
The Clinical Pharmacy Anticoagulation Service (CPAS) at Kaiser Permanente Colorado grew from a single pharmacist assisting a single physician to a comprehensive service staffed by over 20 employees. CPAS provides care for over 7200 patients with each CPAS pharmacist managing all aspects of anticoagulation therapy for 150 to 500 patients. Unique aspects of CPAS include its centralized organization structure, the use of telepharmacy, collaboration drug therapy management agreement with referring physicians and a robust research agenda. Results of various CPAS research projects have been published in the peer-reviewed medical literature. PMID:18804262
Truong, Teresa; Armor, Becky L
Warfarin is considered a high-risk drug because of its narrow therapeutic window, variability in dose response, and multitude of drug and food interactions. Although travel advice is available for patients who are taking warfarin, it is geared toward patients who are traveling to developed countries and tends to be lacking in detail. We describe a 53-year-old woman with two mechanical heart valves and chronic atrial fibrillation who was taking warfarin for thromboembolism prophylaxis and had plans to travel to Vietnam for 10 weeks. Three days before her departure, she was prescribed amiodarone for long-term use. As a result of the extended duration of her travel and the complexities of warfarin use, the pharmacists who managed the patient's anticoagulation reviewed several aspects of a comprehensive management approach with the patient for a safe international trip. They assessed the patient's thromboembolic and hemorrhagic risks, and determined which other drugs (e.g., enoxaparin, phytonadione), dosages, and adequate supplies would be required along with warfarin, as well as how to safely transport these drugs during travel. In addition, the logistics of effectively monitoring international normalized ratio (INR) levels were evaluated, and methods of managing multiple potential scenarios were carefully planned out. Contact with the patient was made through pharmacist-directed telephone visits throughout the travel period. A total of 12 telephone visits were conducted with the patient during the 10 weeks of travel. Her INR was supratherapeutic on three occasions and was subtherapeutic once; however, neither enoxaparin nor phytonadione were needed during the travel period, and the patient returned safely to the United States. Effective and safe use of high-risk drugs for patients leaving the United States requires extensive pretravel planning, and pharmacists can play a central role in optimizing therapeutic outcomes for these patients during international travel
Stanley M. Gartler
In 1914, H. J. Muller postulated the origin of the Y chromosome as having resulted from restricted recombination between homologous sex chromosomes in the male and the accumulation of deleterious mutations. This evolutionary process leads to dosage compensation. This article lays out a brief history of dosage compensation in genetics.
Park, Joon-Sung; Kim, Gheun-Ho; Kang, Chong Myung; Lee, Chang Hwa
Background/Aims Short hemofilter survival and anticoagulation-related life-threatening complications are major problems in systemic anticoagulation with heparin (SAH) for continuous renal replacement therapy (CRRT). The present study examined if regional anticoagulation with citrate (RAC) using commercially available solutions can overcome the associated problems of SAH to produce economical benefits. Methods Forty-six patients were assigned to receive SAH or RAC. We assessed the coagulation ...
Conte, R R; Kehoe, W A; Nielson, N; Lodhia, H
A pharmacist-managed anticoagulation clinic is described, and information on patient outcome during a nine-year period is presented. Since 1974, a pharmacist has managed an anticoagulation clinic for ambulatory patients and inpatients at San Francisco General Hospital Medical Center. The pharmacist's primary responsibilities include the following: educating patients about their diseases and the importance of drug therapy, monitoring patients' vital signs, performing physical examinations, and adjusting warfarin dosage to maintain prothrombin times within the therapeutic range (1.7-2.5 times normal using control values of 1.0-1.2). These patients are also under the care of their primary physicians. The pharmacist's work is checked by the chief of the cardiac clinic at the end of each clinic session. The effectiveness of the pharmacist in managing clinic patients is reviewed periodically; from January 1975 through June 1984, the pharmacist had treated 140 patients (141 courses of therapy). Of 1792 prothrombin times taken during this time, 1060 (59.2%) were within the therapeutic range of 17-25 seconds, 510 (28.5%) were less than 17 seconds, and 222 (12.4%) were greater than 25 seconds. Only four major hemorrhagic events (0.002 hemorrhages per patient-treatment month) and 89 minor events (0.05 hemorrhages per patient-treatment month) occurred. The recurrence rate of thromboembolic events was 0.007 per patient-treatment month. Pharmacist-managed warfarin therapy in these clinic patients resulted in a level of anticoagulation control and morbidity that was acceptable to physicians. PMID:3788996
Full Text Available Carole Decker,1 Linda Garavalia,2 Brian Garavalia,1 Teresa Simon,3 Matthew Loeb,4 John Spertus6, William Daniel51Mid America Heart Institute at Saint Luke's Hospital in Kansas City Missouri, University of Missouri-Kansas City School of Nursing, 2University of Missouri-Kansas City School of Pharmacy, Kansas City, MO, 3Bristol-Myers Squibb, Princeton, NJ, 4Plaza Primary Care and Geriatrics, 5Saint Luke's Cardiovascular Consultants, Kansas City, MO, 6Mid America Heart Institute at Saint Luke's Hospital in Kansas City Missouri, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USABackground: Warfarin, the most commonly used antithrombotic agent for stroke prophylaxis in atrial fibrillation (AF, requires regular monitoring, frequent dosage adjustments, and dietary restrictions. Clinicians' perceptions of barriers to optimal AF management are an important factor in treatment. Anticoagulation management for AF is overseen by both cardiology and internal medicine (IM practices. Thus, gaining the perspective of specialists and generalists is essential in understanding barriers to treatment. We used qualitative research methods to define key issues in the prescription of warfarin therapy for AF by cardiology specialists and IM physicians.Methods and results: Clinicians were interviewed to identify barriers to warfarin treatment in a large Midwestern city. Interviews were conducted until thematic saturation occurred. Content analysis yielded several themes. The most salient theme that emerged from clinician interviews was use of characteristics other than the patient's CHADS2 score to enact a treatment plan, such as the patient's social situation and past medication-taking behavior. Other themes included patient knowledge, real-world problems, breakdown in communication, and clinician reluctance.Conclusion: Warfarin treatment is associated with many challenges. The barriers identified by clinicians highlight the unmet need associated
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
This global map of Mars shows the estimated radiation dosages from cosmic rays reaching the surface, a serious health concern for any future human exploration of the planet.The estimates are based on cosmic-radiation measurements by the Mars radiation environment experiment, an instrument on NASA's Mars 2000 Odyssey spacecraft, plus information about Mars' surface elevations from the laser altimeter instrument on NASA's Mars Global Surveyor. The areas of Mars expected to have the lowest levels of cosmic radiation are where the elevation is lowest, because those areas have more atmosphere above them to block out some of the radiation. Earth's thick atmosphere shields us from most cosmic radiation, but Mars has a much thinner atmosphere than we have on Earth.The colors in the map refer to the estimated annual dose equivalent in rems, a unit of radiation dose. The range is generally from 10 rems(color-coded dark blue) to 20 rems (color coded dark red). Radiation exposure for astronauts on the International Space Station in Earth orbit is typically equivalent to an annualized rate of 20 to 40 rems.NASA's Jet Propulsion Laboratory, Pasadena, Calif. manages the 2001 Mars Odyssey and Mars Global Surveyor missions for NASA's Office of Space Science, Washington D.C. The Mars radiation environment experiment was developed by NASA's Johnson Space Center, Houston. Lockheed Martin Astronautics, Denver, is the prime contractor for Odyssey, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.
蒋晨阳; 赵莉莉; 王建安; 单江; MOHAMMODBalgaith
Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoag-ulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were random-ly assigned into two groups. Anticoagulation group( Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50 - 70 seconds. Non-anticoagulation group( Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1 (PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded.Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups ( P 0.05) . Three patients in Group A and 2 patients in Group B developed minor limb ischemia( P > 0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B ( P <0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.
JIANG Chen-yang(蒋晨阳); ZHAO Li-li(赵莉莉); WANG Jian-an(王建安); SAN Jiang(单江); MOHAMMOD Balgaith
Objective: To investigate if intra-aortic balloon pump(IABP) is contraindicated without anticoagulation therapy. Methods: Some 153 IABP patients in the King Abdulaziz Cardiac Center(KSA) were randomly assigned into two groups. Anticoagulation group(Group A) consisted of 71 patients who were given heparin intravenously with target aPTT 50-70 seconds. Non-anticoagulation group(Group B) consisted of 82 patients without intravenous heparin during balloon pumping. Hematological parameters including platelet count, D-dimer, Plasminogen activator inhibitor-1(PAI-1) and fibrinogen degradation products(FDP) were checked respectively at the point of baseline, 24 hours, 48 hours and 24 hours post IABP counterpulsation. Clot deposits on balloon surface, vascular complications from IABP including bleeding and limb ischemia were recorded. Results: Platelet count and PAI-1 level decreased at 24 hours and 48 hours in both groups (P0.05). Three patients in Group A and 2 patients in Group B developed minor limb ischemia(P>0.05). No major limb ischemia in either group. Two patients in Group A suffered major bleeding and required blood transfusion or surgical intervention, whereas no patient had major bleeding in Group B. Eight patients had minor bleeding in Group A, but only 2 patients in Group B(P<0.05). No clot deposit developed on IABP surface in either group. Conclusion: IABP is safe without routine anticoagulation therapy. Selecting appropriate artery approach and early detection intervention are key methods for preventing complications.
Full Text Available Anticoagulation Clinics (ACs are services specialized in management of patients on anticoagulant treatment. At present, ACs manage patients chiefly on antivitamin K antagonists (AVKs, but patient population has already changed in the last few years, because of an increase of treatments with other anticoagulant drugs, which require different management systems. The strong increase in the number of patients at AC, mainly on long-term treatment, has determined the development of web management, through telemedicine systems, improving the quality of life and maintaining the same clinical quality levels. New oral anticoagulants (NOAs have shown to be as effective as AVK antagonists in stroke prevention in atrial fibrillation and for treatment of venous thromboembolism in addition to VTE prophylaxis in orthopaedic surgery, when administered at a fixed dose, but patient adherence and compliance are crucial for good quality treatment. At present, lacking data from the real world, an oversimplification of treatment with NOAs could cause unjustified risks for patients and also a possible future underuse of good drugs. For these reasons the vigilance must be high and ACs can have a crucial role in defining which is the best management for NOA patients and how to do it, as it happened for AVKs.
Rangnekar, Abhijit; Zhang, Alex M.; Shiyuan Li, Susan; M. Bompiani, Kristin; Hansen, Majken Nørgaard; Gothelf, Kurt Vesterager; Sullenger, Bruce A; LaBean, Thomas H.
Control over thrombin activity is much desired to regulate blood clotting in surgical and therapeutic situations. Thrombin-binding RNA and DNA aptamers have been used to inhibit thrombin activity and thus the coagulation cascade. Soluble DNA aptamers, as well as two different aptamers tethered by a flexible single-strand linker, have been shown to possess anticoagulant activity. Here, we link multiple aptamers at programmed positions on DNA nanostructures to optimize spacing and orientation o...
Markussen, Mette D.; Heiberg, Ann-Charlotte; Nielsen, Robert;
Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement......Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement...
Salvador, Juan Pablo; Marco, María Pilar
[EN] The present invention relates to the design of haptens that are structurally related to coumarin oral anticoagulant compounds (COAC), to be used for the production of specific antibodies against said type of substances and the subsequent use thereof for the development of diagnosis tools for use in laboratories or in point-of-care (PoC) devices. In particular, the produced antibodies have been used to develop a diagnosis tool that enables the plasma levels of COAC to be quantified in pat...
Drozd, N N; Tolstenkov, A S; Makarov, V A; Miphtakhova, N T; Voyushina, T L; Sergeev, M E
Original synthetic peptide derivatives exhibit anticoagulant activity in vitro and in vivo. They delayed fibrin clot formation from human blood plasma in tests for the intrinsic coagulation pathway (activated partial thromboplastin time) and final stage of plasma coagulation (thrombin time) and inhibited amidolytic activity of thrombin. We determined the minimum effective dose of the most active compound providing a 2-fold lengthening of blood clotting time (activated partial thromboplastin time test and thrombin time test), which persisted for 2-3 h. PMID:19024001
Borst, G H A; Counotte, G H M
Second-generation anticoagulant rodenticides can give rise to unexpected casualties in nontarget species in zoos. The first two offspring of a pair of turkey vultures (Cathartes aura) died of brodifacoum toxicosis. The adult birds fed rodenticide-killed mice to their offspring. There are previous case reports of small carnivorous birds (Dacelo novae-guinae and Tockus deckeni) killed eating poisoned (difenacoum and brodifacoum) mice. Even a granivorous species (Rollulus roulroul) died, probably by contamination of its food by cockroaches that transported the rodenticide. PMID:12216801
Full Text Available Cecilia Becattini, Alessandra Lignani, Giancarlo AgnelliInternal and Cardiovascular Medicine and Stroke Unit, University of Perugia, ItalyAbstract: Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future.Keywords: anticoagulant therapy, antithrombotic therapy, anticoagulants, direct thrombin inhibitors, factor Xa inhibitors
Atrial fibrillation (AF) increases the risk of stroke.New anticoagulation agents have recently provided alternative and promising approaches.This paper reviews the current state of anticoagulation therapy in AF patients,focusing on various clinical scenarios and on comparisons,where possible,between western and eastern populations.
Rasmussen, Rune Skovgaard; Corell, Pernille; Madsen, Poul;
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 the...
Weinstock, Matthew J; Uhlmann, Erik J; Zwicker, Jeffrey I
Both venous thromboembolism and intracranial metastases are common complications in the setting of primary brain tumors and metastatic malignancies. Anticoagulation is indicated in the presence of cancer-associated thrombosis in order to limit the risk of pulmonary embolism; however, there is reluctance to initiate anticoagulation in the setting of intracranial metastatic disease due to potential for intracranial hemorrhage. Recent evidence suggests that therapeutic anticoagulation can be safely administered in the setting of metastatic brain tumors. This review examines the current understanding of the pathophysiology of intracranial hemorrhage in malignancy, describes the incidence of intracranial hemorrhage in the setting of brain tumors with therapeutic anticoagulation, and outlines management strategies relevant to the treatment of intracranial hemorrhage in the setting of anticoagulation. PMID:27067980
Caio Julio Cesar dos Santos Fernandes
Full Text Available Worldwide, venous thromboembolism (VTE is among the leading causes of death from cardiovascular disease, surpassed only by acute myocardial infarction and stroke. The spectrum of VTE presentations ranges, by degree of severity, from deep vein thrombosis to acute pulmonary thromboembolism. Treatment is based on full anticoagulation of the patients. For many decades, it has been known that anticoagulation directly affects the mortality associated with VTE. Until the beginning of this century, anticoagulant therapy was based on the use of unfractionated or low-molecular-weight heparin and vitamin K antagonists, warfarin in particular. Over the past decades, new classes of anticoagulants have been developed, such as factor Xa inhibitors and direct thrombin inhibitors, which significantly changed the therapeutic arsenal against VTE, due to their efficacy and safety when compared with the conventional treatment. The focus of this review was on evaluating the role of these new anticoagulants in this clinical context.
Anticoagulant therapy is the cornerstone of treatment of venous thromboembolism (VTE). The treatment needs rapid initial anticoagulaton to minimize the risk of thrombus extension and fata pulmonary embolism, followed by an extended anticoagulation, aimed at preventing recurrent VTE. Till very recently, immediate anticoagulation can only be achieved with parenteral agents, such as heparin, low-molecular-weight heparin, or fondaparinux. Extended treatment usually involves the administration of vitamin K antagonists, such as warfarin. Emerging direct oral anticoagulants have the potential to streamline VTE treatment. These agents include oral anticoagulants that target thrombin or factor Xa. This article reviews the characteristics of these agents, describes the results of clinical trials in venous thromboembolic disease and outlines their strengths and weakness. PMID:24167902
Full Text Available Traditional anticoagulants, such as low molecular weight heparin, unfractionated heparin, fondaparinux and vitamin K antagonists, have been the mainstay of treatment of venous thromboembolism (VTE in the clinical hospital setting and after discharge. These anticoagulants are effective, but are associated with some limitations that may lead to their underuse in many settings. Based on the results of large, randomized clinical trials, new oral anticoagulants have been validated for the treatment of acute deep vein thrombosis and pulmonary embolism, and for the prevention of recurrent VTE. These drugs represent a landmark shift in anticoagulation care and may overcome some of the limitations of traditional agents, with the potential of improving adherence to anticoagulation therapy.
Ciurus, Tomasz; Sobczak, Sebastian; Cichocka-Radwan, Anna
Oral direct inhibitors of thrombin and activated factor Xa are approved as new anticoagulant drugs. In contrast to vitamin K antagonists (VKA) and heparins, the new agents have single targets in the coagulation cascade and more predictable pharmacokinetics, but they lack validated and available antidotes. Unlike VKA, they do not require routine monitoring of coagulation. However, the measurement of their pharmacologic effects might be of value in selected patients. They interfere with the routine coagulation tests, which should be interpreted with caution. Specific tests exist and can be used in case of emergencies. Adequate supportive care and temporary removal of all antithrombotic agents constitute the basis for management of serious bleeding complications. The administration of coagulation factors, such as fresh frozen plasma, prothrombin complex concentrates or recombinant activated FVII, can benefit in life-threatening bleeding or emergency surgery. Specific antidotes for non-vitamin K oral anticoagulants are in clinical development. This review aims at answering in a brief and simplified manner some clinical questions. PMID:26336492
E. N. Bochanova
A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.
E. N. Bochanova
Full Text Available A complex system of hemostasis regulation, insufficient data on drugs pharmacokinetics, multiple factors effecting treatment, including patient’s adherence to therapy, that can lead to the need for the dosage regimen specification are presented.
Andrews, Gavin P
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. PMID:17855217
Martha L. González-Bárcenas
Full Text Available The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results.
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.
This review attempts to answer the common questions faced by a clinician regarding thromboembolism and thromboprophylaxis in patients following Fontan surgery. The review is in an easy to understand question and answer format and discusses the currently available literature on the subject in an attempt to arrive at practical clinically relevant solutions. Patients who have undergone the Fontan operation are at a high risk for thromboembolism. Based on available evidence, there is a strong rationale for thromboprophylaxis. However, it is not clear as to which agent should be administered to prevent thromboembolic events. While the available evidence suggests that antiplatelet agents alone may be as good as oral anticoagulants, there is a need for a large multicenter randomized control trial comparing these two common strategies to deliver a clear verdict. PMID:27625521
Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J
Heparin and low molecular weight heparins are major clinical anticoagulants and the drugs of choice for the treatment of deep venous thrombosis. The discovery of an antithrombin binding domain in heparin focused interest on understanding the mechanism of heparin's antithrombotic/ anticoagulant activity. Various heparin-mimetic oligosaccharides have been prepared in an effort to replace polydisperse heparin and low molecular weight heparins with a structurally-defined anticoagulant. The goal of attaining a heparin-mimetic with no unwanted side-effects has also provided motivation for these efforts. This article reviews structure-activity relationship (SAR) of structurally-defined heparin-mimetic oligosaccharides. PMID:14529394
Eduardo B. Saad
Full Text Available Atrial fibrillation is associated with thromboembolic events that may cause important impairment on quality of life. Pulmonary vein isolation is the treatment of choice in cases that are refractory to medical therapy. Once sheaths and catheters are manipulated inside the left atrium, anticoagulation with heparin must be used during the procedure to protect patients from thromboembolic phenomena. Different strategies of anticoagulation are used at different centers. This review summarizes the pathophysiology of thrombus formation in the left atrium, defines which patients are under high risk and describes the main strategies used for anticoagulation.
Lewis, S M; Kroner, B A
The literature describing pharmacy involvement with anticoagulation services primarily does not include information about patients' perceptions of this involvement. A 22-question survey was developed and administered to 296 patients enrolled in the anticoagulation clinic at the VA Pittsburgh Health Care System. Excluded patients had fewer than four clinic visits or were followed outside of the anticoagulation clinic. The study period was nine weeks and any missed patients were telephoned. The median response to each question was determined. Similar questions were analyzed for acquiescent trends. Results indicate that, overall, patients are comfortable with pharmacists providing warfarin monitoring and dose adjustments. PMID:10174757
Full Text Available Vitamin K antagonists (VKA are among the most widely prescribed drugs in the industrialized world. In fact, for decades, VKA have been the only orally available anticoagulant for the primary and secondary prevention of venous and arterial thrombotic events. Their efficacy has been widely demonstrated in a series of studies carried out in the 1990s. Since the incidences of atrial fibrillation and venous thromboembolism increase exponentially with age, the number of anticoagulated patients is destined to increase. This paper examines anticoagulation therapy management with particular attention to the use of VKA.
Bungard, Tammy J; Gardner, Leslie; Archer, Stephen L.; Hamilton, Peter; Ritchie, Bruce; Tymchak, Wayne; Tsuyuki, Ross T.
Background Anticoagulation management services (AMSs) are widely used for anticoagulation management in many countries. Our AMS is a pharmacist-run ambulatory clinic with a physician advisory committee that manages patients referred with complicated anticoagulation histories. This paper assesses the adequacy of anticoagulation, rates of anticoagulant-related events and associated health care resource utilization for patients before and after referral to our AMS. Methods Consecutive patients r...
Full Text Available Background: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE.Methods: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but without arterial hypotension or shock. The patients were randomly assigned in a single-blind fashion to receive an anticoagulant [Enoxaparin (1 mg/kg twice a day] plus a thrombolytic [Alteplase (100 mg or Streptokinase (1500000 u/2 hours] or an anticoagulant [Enoxaparin (1 mg/kg twice a day] alone. The primary endpoint was in-hospital death or clinical deterioration requiring an escalation of treatment. The secondary endpoints of the study were major bleeding, pulmonary hypertension, right ventricular dilatation at the end of the first week, and exertional dyspnea at the end of the first month.Results: Of 50 patients enrolled, 25 patients were randomly assigned to receive an anticoagulant plus a thrombolytic and the other 25 patients were given an anticoagulant alone. The incidence of the primary endpoints was significantly higher in the anticoagulant-alone group than in the thrombolytic-plus-anticoagulant group (p value = 0.022. At the time of discharge, pulmonary artery pressure was significantly higher in the anticoagulant-alone group than in the thrombolytic- plus-anticoagulant group (p value = 0.018; however, reduction in the right ventricular size or normalization of the right ventricle showed non-significant differences between the two groups. There was no significant difference regarding the New York Heat Association (NYHA functional class between the two groups at the end of the first month (p value = 0.213. No fatal bleeding or cerebral bleeding
Jones, Sophie; McLoughlin, Siobhan; Piovesan, Dana; Savoia, Helen; Monagle, Paul; Newall, Fiona
The complexity of managing children with chronic disease has led to an increase in the use of long-term warfarin therapy. Time in therapeutic range (TTR) is the preferred method for determining efficacy and stability of warfarin management. This study aimed to determine the TTR achievement and incidence of adverse events among pediatric warfarin patients managed by an anticoagulation clinic over 12 months and to compare TTR achievement between patients self-testing (PST) at home and those monitored using routine methods. International normalized ratio (INR) results reported for 2012 for children currently having their warfarin therapy managed by a dedicated pediatric anticoagulation clinic were analyzed. Warfarin-related adverse events were recorded. A total of 164 patients were included. In total, 93 children performed PST and 71 children tested their INR at a hospital or pathology service. TTR achievement for the cohort was 67.1% (95% confidence interval, 64.4-69.7). A total of 69.2% of INR tests conducted at home were within the TTR compared with 64.3% of INR tests conducted at a hospital or pathology service (P=0.07). One major bleeding event occurred and there was 1 thrombotic episode. PST demonstrated noninferior warfarin stability compared with routine methods. Routine outcome evaluation of pediatric anticoagulation management within single institutions is necessary to confirm the success of such programs. PMID:26808370
Lassen, Michael R
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, such as their...
Dimova, Cena; Evrosimovska, Biljana; Pandilova, Maja; Kovacevska, Ivona; Zabokova-Bilbilova, Efka
Aim of this study is to review the evidence of different therapy approach, to highlight the areas of major concern and to suggest specific oral surgery treatment for patients on oral anticoagulants. The aim of operative treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may...
Dimova, Cena; Papakoca, Kiro; Kovacevska, Ivona; Kamceva, Gordana
INTRODUCTIONS: The oral surgeons are frequently asked to manage patients who are receiving oral anticoagulants. The goal of treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. AIM:However, this practice may logically increase the risk of a potentially life-threatening thromboembolism. Thus, thi...
The oral and maxillofacial surgeons are frequently asked to manage patients who are receiving oral anticoagulants. The goal of treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment 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. Thus, this is...
The oral and maxillofacial surgeons are frequently asked to manage patients who are receiving oral anticoagulants. The goal of treatment is to minimize the risk of hemorrhage while continuing to protect the patient against thromboembolism formation. The ordinary treatment 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. Thus, this is...
Marcelo Kropf; Cleidson Alves Bergami; Felipe Dias Leal; Claudia Oliveira Dias Passos; Zilda de Santana Gonsalves; Isabela Laudares Marques; Isabela Azevedo Mota; Marcele Lima Monte Gonçalves
Anticoagulant therapy is essential for the prevention of risks associated with the formation of thrombus in patients after surgery, especially in orthopedics. Recently, new oral anticoagulants were introduced in the therapeutic arsenal. This fact is important, because the current drug of choice in clinical practice is enoxaparin, a low molecular weight heparin. As all injecting drugs, enoxaparin may reduce patients' adherence to treatment by dissatisfaction with and resistance to the administ...
Dimova, Cena; Evrosimovska, Biljana; Papakoca, Kiro; Georgiev, Zlatko; Angelovska, Bistra; Ristoska, Sonja
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...
Barrios, Annette C.; Ventura, Hector O.; Milani, Richard V.
Clinical privileging of pharmacists and the effective use of support staff and information technology have helped create an efficient pharmacist-operated anticoagulation clinic at Ochsner Clinic Foundation that will support future growth efforts for improved patient care. Developed by Ochsner's Department of Cardiology, the pharmacist-operated anticoagulation clinic cares for 2000 patients with a clinical pharmacist, staff pharmacist, registered nurse, and medical assistants. Patients are man...
VALCHEV, Ivan; Binev, Rumen; YORDANOVA, Veska; Nikolov, Yordan
The newest measures for the control of harmful rodent populations are from the anticoagulant rodenticide group, which are divided into 2 subgroups: first and second generations, and indandione derivatives. Non-target organisms are potentially at risk of direct consumption of baits (primary hazard) and of eating poisoned rodents (secondary hazard). Anticoagulant rodenticides inhibit the enzyme vitamin K-dependent carboxylase and thus impair the reactivation of vitamin K1, indirectly affecting ...
Prashanth Panduranga; Mohammed El-Deeb; Chitra Jha
Choosing the best anticoagulant therapy for a pregnant patient with a mechanical prosthetic valve is controversial and the published international guidelines contain no clear-cut consensus on the best approach. This is due to the fact that there is presently no anticoagulant which can reliably decrease thromboembolic events while avoiding damage to the fetus. Current treatments include either continuing oral warfarin or substituting warfarin for subcutaneous unfractionated heparin or low-mole...
Fadi Shamoun; Hiba Obeid; Harish Ramakrishna
Atrial fibrillation continues to be a significant source of morbidity and mortality worldwide. Effective anticoagulation remains the cornerstone of outpatient and inpatient treatment. The use of the new generation of anticoagulants (NOACs) continues to grow. Recently published data indicate their cost-effectiveness and overall safety in stroke prevention; compared to vitamin K antagonists, they can be prescribed in fixed doses for long-term therapy without the need for coagulation monitoring....
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
Becattini, Cecilia; Lignani, Alessandra; Agnelli, Giancarlo
Anticoagulant drugs have an essential role in the prevention and treatment of thromboembolic diseases. Currently available anticoagulants substantially reduce the incidence of thromboembolic events in a number of clinical conditions. However, these agents have limitations that strengthen the case for the development of new anticoagulants. An ideal anticoagulant should be at least as effective as those currently in use, as well as safe, simple to use, and widely applicable. The majority of new anticoagulants currently under investigation are small molecules with a selective and direct anti-Xa or antithrombin action, allowing oral administration in fixed doses. These new agents are in different phases of clinical development. The anti-Xa agent rivaroxaban and the antithrombin agent dabigatran are already available for the prophylaxis of venous thromboembolism in some countries. Apixaban is in an advanced phase of clinical development and several anti-Xa agents are currently approaching phase III clinical trials. Promising results in terms of efficacy and safety profiles have been obtained with these agents in different clinical conditions. Differences in pharmacokinetics and pharmacodynamics could offer the potential for individualized anticoagulant therapies in the near future. PMID:20531960
Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A
Adequate anticoagulant therapy is a general approach to treatment of deep vein thrombosis. However, the duration of anticoagulant therapy is not strictly specified in everyday clinical practice. The present article deals with various approaches to selecting the duration of therapy with anticoagulants based on the findings of studies, national and foreign clinical guidelines. The minimal duration of therapy for deep vein thrombosis and pulmonary thromboembolism amounts to 3 months in accordance with the national and American recommendations. For some cohorts of patients, continuation of therapy above 3 months is considered: patients with idiopathic thrombosis (the recommended duration of therapy of not less than 6 months), patients having persisting risk factor for relapse of thrombosis on termination of the main therapeutic course, oncological patients (6 month therapy followed by assessing the risk and benefit of continuing therapy with anticoagulants). Prolonged therapy of venous thromboembolism using unfractionated heparin or low-molecular-weight heparin followed by changing over to vitamin K antagonists is associated with decreased risk for thrombosis relapse approximately by 90%, however increasing the risk of haemorrhage. Currently, as an alternative, it is possible to consider administration of novel oral anticoagulants (rivaroxaban, dabigatran, apixaban) which beside high efficacy are associated with less risk of bleeding. The route of administration, no necessity to control the INR, and the minimal number of drug and food interactions make administration of new oral anticoagulants an attractive alternative to therapy with heparins and vitamin K antagonists. PMID:27100556
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.
Elung-Jensen, Thomas; Heisterberg, Jens; Sonne, Jesper;
concentration of enalaprilat afforded the same degree of renoprotection, blood pressure control and minimisation of proteinuria as a high concentration, during 12 months of follow-up. The high-dosage treatment was associated with a more pronounced tendency to hyperkalaemia. Thus, there seems to be no indication...
Hamada, Yukihiro; Kawasumi, Noriyo; Hirai, Jun; Yamagishi, Yuka; Mikamo, Hiroshige
Voriconazole (VRCZ), a broad-spectrum triazole, is served in two dosage forms-injection and oral. VRCZ is difference dosage of oral and intravenous administration writing a medical package insert in Japan. 6 mg/kg intravenous injection (IV) twice daily for first day as initial loading dose, followed by 3-4 mg/kg IV twice daily between meals is recommended. 300 mg orally twice daily for first day as initial loading dose, followed by 150-200 mg orally twice daily between meals is recommended. Patients weighing over 40 kg, 200 mg orally twice daily between meals is recommended. Patients weighing under 40 kg, 100 mg orally twice daily between meals is recommended, increase to 150 mg twice daily if inadequate response. This study evaluated VRCZ trough concentration and oral dosage in the 23 cases which administered VRCZ to analysis for TDM in Aichi University Hospital. Spearman rank correlation coefficient was calculated to examine relationships among variables. The level of statistical significance was set at p=0.05. All data were analyzed and processed on JMP 8 (SAS Institute Japan). There was a significant positive correlation between VRCZ trough concentration and dose/weight (r=0.47 poral dosage is appropriate to administer dose/weight (mg/kg) twice a day as same as IV. PMID:25566590
Maryam Taherkhani; Adineh Taherkhani; SeyedReza Hashemi; Taraneh Faghihi-Langroodi; Roxana Sadeghi; Mohammadreza Beyranvand
Background: The use of thrombolytic agents in the treatment of hemodynamically stable patients with acute submassive pulmonary embolism (PTE) remains controversial. We, therefore, conducted this study to compare the effect of thrombolytic plus anticoagulation versus anticoagulation alone on early death and adverse outcome following submassive PTE.Methods: We conducted a study of patients with acute pulmonary embolism and pulmonary hypertension or right ventricular dilatation/dysfunction but w...
Enriquez, Andres; Lip, Gregory Y H; Baranchuk, Adrian
In recent years, non-vitamin K oral anticoagulants (NOACs) have emerged as an alternative to warfarin for the prevention and treatment of thrombo-embolic disease. Large randomized trials have demonstrated that these agents, which act by directly targeting thrombin (dabigatran) and factor Xa....... New specific antidotes (e.g. idarucizumab, andexanet alfa, and ciraparantag) show promising data, and may soon become available for clinical use. In this article, we review the pharmacology of these agents, the incidence and outcomes of haemorrhagic complications, the available strategies for...
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
Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars;
-hospital mortality was 23% (95% CI: 17-29%), and there was no significant difference between those with or without anticoagulation. CONCLUSIONS: We found no increased risk of cerebral haemorrhage in S. aureus IE patients receiving anticoagulation. Anticoagulation was associated with a reduced risk of cerebral events...... before initiation of antibiotics. Data support the continuance of anticoagulation in S. aureus IE patients when indicated.......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...
Tantawy, Mahmoud A.; El-Ragehy, Nariman A.; Hassan, Nagiba Y.; Abdelkawy, Mohamed
Apixaban (a novel anticoagulant agent) was subjected to a stress stability study including acid, alkali, oxidative, photolytic, and thermal degradation. The drug was found to be only liable to acidic and alkaline hydrolysis. The degradation product was then isolated and identified by IR and GC-mass spectrometry. Four spectrophotometric methods, namely; first derivative (D1), derivative ratio (DR), ratio difference (RD) and mean centering of ratio spectra (MCR), have been suggested for the determination of apixaban in presence of its hydrolytic degradation product. The proposed methods do not require any preliminary separation step. The accuracy, precision and linearity ranges of the proposed methods were determined, and the methods were validated as per ICH guidelines and the specificity was assessed by analyzing synthetic mixtures containing different percentages of the degradation product with the drug. The developed methods were successfully applied for the determination of apixaban in bulk powder and its tablet dosage form.
Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P.; Ismail, Farooq
Objective 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. Methods 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. Results International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin 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. Conclusion 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. PMID:27152278
Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele
This study evaluates the presence of anticoagulant rodenticides in animals with a diagnosis of suspected poisoning and in bait samples. The survey was carried out from 2010 to 2012, in 2 regions of South Italy (Puglia and Basilicata) on 300 organs of animals and 90 suspected bait samples. The qualitative and quantitative analyses were conducted using an analytical method based on high‑performance liquid chromatography (HPLC) with fluorimetric detection (FLD) for the simultaneous determination of 8 anticoagulant rodenticides (bromadiolone, brodifacoum, coumachlor, coumafuryl, coumatetralyl, difenacoum, flocoumafen, and warfarin). The presence of anticoagulant rodenticides was detected in 33 organs of animals (11% of the total) and 6 bait samples (7% of the total). The most commonly detected compound was coumachlor (47% of 39 positive samples) followed by bromadiolone (24%), and brodifacoum (11%). The species mostly involved in anticoagulant rodenticide poisoning were dogs and cats. This study emphasizes the relevance of the determinations of anticoagulant rodenticides in cases of suspected poisoning in veterinary practice. PMID:27393877
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.
Klein, Jeffrey A.; Jeske, Daniel R.
BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses wer...
Burrell, C D
The realities of the marketplace dictate that pharmaceutical companies seek to develop higher unit dosage forms. Technical problems not infrequently hinder such development. In low doses once-a-day medication with psychotropics is possible and practical. The potential for adverse reactions frequently renders it desirable to divide higher daily doses into two separate doses, one given in the morning and the other in the evening. PMID:1233527
Full Text Available The new oral direct anticoagulants (DOACs could represent a new frontier for management of thromboembolic diseases. However, the new drugs have limitations that need to be considered. Despite the fact that their efficacy and safety profile are at least not inferior to comparators, bleeding risk represents the most feared complication, as for all the antithrombotic drugs. Bleeding risk increases with conditions that interfere with pharmacokinetics, in addition to the risk strictly linked to patients or their co-morbidities. Since all DOACs are excreted from kidneys (even though at different percentages according to the different molecules, renal impairment represents one of the leading causes of DOACs accumulation and bleeding risk. Moderate renal failure is the main condition in which dose adjustment of DOACs could be required, while severe renal impairment represents an absolute contraindication for their use. Renal function must, therefore, be carefully monitored before prescription and during assumption. The older population is at higher bleeding risk, and dose adjustment of DOACs could be required. Although to a lesser degree than oral anticoagulant vitamin K antagonists, DOACs can have drug interactions, especially with P-glycoprotein and cytochrome P3A4 inducers or inhibitors, and these interactions must be taken into account in real practice to avoid accumulation or under dosage. The concomitant use of other drugs, especially antithrombotics, may expose the patients to bleeding risk by reducing the hemostatic properties.
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
Dilute Russell's viper venom (DRVV) testing and activated partial thromboplastin time (APTT) have been effectively used in combination for lupus anticoagulant testing. The purpose of our study was to evaluate the role of mixing in activated partial thromboplastin and dilute Russell's viper venom testing for evaluation of lupus anticoagulants. Citrated blood from patients who were not on oral anticoagulant therapy was studied. Mixing study with 1 : 1 normal plasma for elevated APTT and also few samples with elevated screen time was carried out. Elevated APTT was seen in only 48.1% of patients with lupus anticoagulant. Correction of APTT was seen in 27.8% of lupus anticoagulant-positive patients. DRVV test on mixing resulted in 83.8% false-negative values. Integrated DRVV test could be a standalone test for testing lupus anticoagulant. Mixing study may be restricted for patients on oral anticoagulants or patients with strong lupus anticoagulant. PMID:26626041
Haustein, K O
Anticoagulants of the cumarin-type (warfarin, phenprocoumon, and acenocoumarol) are drugs for the long-term treatment and prevention of thromboembolic disorders. Because of their narrow therapeutic range, many patients have bleedings of variable severity or have recurrent thrombotic events. For this reason, the study of the pharmacokinetic parameters of phenprocoumon (PPC), considering its influence on blood clotting factors, is of high interest. The elimination kinetics of PPC, its interaction with phytomenadion (vitamin K), and the pharmacokinetic behavior of the anticoagulant under steady-state conditions have been investigated in studies with healthy volunteers and patients taking anticoagulants. The maintenance dose and the plasma levels of PPC were correlated with prothrombin time (PT) in 89 patients treated with PPC. Varying parameters in each patient (e.g., elimination kinetics of PPC, activity of the cumarin-dependent blood-clotting factors, endogenous phytomenadion stores), render it impossible to use a different means of monitoring than that of PT determination. PMID:10327214
Nutescu, Edith A; Shapiro, Nancy L; Chevalier, Aimee; Amin, Alpesh N
For over 50 years, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to traditional agents such as unfractionated heparin and oral vitamin K antagonists such as warfarin. These traditional agents are fraught with limitations that complicate their clinical use. A variety of novel anticoagulants with improved pharmacologic and clinical profiles have recently been introduced or are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of low-molecular-weight heparins, factor Xa inhibitors, and direct thrombin inhibitors. Because of their convenience and ease of use, some of these novel compounds are competing with the traditional anticoagulants and are needed additions to the antithrombotic arsenal. PMID:15853173
Full Text Available The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives.Objective: To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing.Method: A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009. Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials.Results: Data were collected for 67 patients treated with either warfarin (n=46 or enoxaparin (n=21 for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF, 34.8% (VTE; enoxaparin: 100%, (VTE. The use of dabigatran in VTE/stroke prevention was found to be more cost-effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33% were factored into costing.Conclusion: This study highlights the potential cost-effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients.
Wilt, V M; Gums, J G; Ahmed, O I; Moore, L M
The primary objective of this study was to determine if a pharmacist-managed anticoagulation monitoring service (AMS) improved the outcomes of patients receiving warfarin in a family practice setting and was cost effective in treating and preventing thromboembolic disorders. A retrospective chart review was performed on all patients at the University of Florida's Family Practice Residency Program who received warfarin pharmacotherapy between October 1, 1988, and December 15, 1993. The outcomes of patients followed by AMS were compared with those of a control group consisting of patients receiving warfarin but followed only by their physician. Outcomes were evaluated based on the number of thromboembolic and hemorrhagic events, as well as unplanned clinic visits, emergency room visits, and hospital admissions. Cost of hospital admissions, emergency room visits, and participation in the AMS were analyzed. During 28 person-years of treatment, control subjects sustained 12 thromboembolic events (2 pulmonary embolisms, 1 cerebrovascular accident, and 9 deep venous thromboses) and 2 minor and 5 major hemorrhagic events. The study group reported two minor hemorrhagic events during a total of 60 person-years. The control group was 20 times more likely than the study group to experience any event (rate ratio 20, 95% CI 5-87). In addition, hospitalization and emergency room charges indicated an actual cost of $119,074.95 for the control group's events. The cost to this group for 28 person-years of participation in the AMS would have been $5040.00. A potential cost avoidance of $4072.68 per person-year of follow-up may have been possible if these patients had been followed by the AMS. A pharmacist-managed AMS in a family practice setting can result in improved outcomes for patients receiving warfarin and is cost effective. PMID:8602380
Feher, G; Illes, Z; Komoly, S; Hargroves, D
(NOACs) have been extensively studied in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and non-valvular atrial fibrillation (NVAF). The aim of our work to review the available evidence for NOACs in the treatment of CVT. Based on our literature search there is insufficient evidence to......Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulants...
Feher, Gergely; Illes, Zsolt; Komoly, Samuel; Hargroves, David
Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with extremely diverse clinical features, predisposing factors, brain imaging findings, and outcome. Anticoagulation is the cornerstone of CVT management, however, it is not supported by high-quality evicence. Novel oral anticoagulants (NOACs) have been extensively studied in patients with deep vein thrombosis, pulmonary embolism and non-valvular atrial fibrillation. The aim of our work was to review the available evidence for NOACs in the treatment of CVT. Based on our literature search there is insufficient evidence to support the use of NOACs in CVT, although case series with rivaroxaban and dabigatran have showed promising results. PMID:25994451
Hankey, Graeme J; Norrving, Bo; Hacke, Werner; Steiner, Thorsten
Each year, 1·0–2·0% of individuals with atrial fibrillation and 0·1–0·2% of those with venous thromboembolism who are receiving one of the novel oral anticoagulants (dabigatran, rivaroxaban, or apixaban) can be expected to experience an acute ischemic stroke. Additionally, 0·2–0·5% of individuals with atrial fibrillation who are receiving one of the novel oral anticoagulants can be expected to experience an intracranial hemorrhage. This opinion piece addresses the current literature and offer...
Soltysiak, Jolanta; Warzywoda, Alfred; Kociński, Bartłomiej; Ostalska-Nowicka, Danuta; Benedyk, Anna; Silska-Dittmar, Magdalena; Zachwieja, Jacek
Background Regional citrate anticoagulation (RCA) is one of the methods used to prevent clotting in continuous renal replacement therapy (CRRT). The aim of this study was to describe the outcomes and complications of RCA-CRRT in comparison to heparin anticoagulation (HA)-CRRT in critically ill children. Methods This study was a retrospective review of 30 critically ill children (16 on RCA- and 14 on HA-CRRT) who underwent at least 24 h of CRRT. The mean body weight of the children was 8.69 ± ...
Pitrák, V; Hadacová, I; Hochová, I; Hoch, J
Chronic anticoagulant treatment is administered mostly for cardiological reasons. Cumarin derivatires are used in the majority of cases (Warfarin, Pelentan). It is necessary to monitor this treatment regularly and to control the dose according to the INR value. Different complications can occur; the haemorrhage represents a serious one. The authors discuss several aspects of anticoagulant therapy and possible prevention of the complications. The importance of the problems is demonstrated on the authors' clinical experience--two cases of haemorrhage after Warfarin administration simulating an acute surgical event. PMID:11482149
D. A. Sychev
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.
Kreutzer, J S; Schneider, H G; Myatt, C R
The effect of alcohol on aggression and assertiveness was examined in 54 men college students. A 2 (high vs low dosage expectancy) x 3 (0.0, 0.5 and 1.0 ml of 95% alcohol per kg of body weight) design was used. There was an increase in self-reported aggression at the moderate dosage but an increase only in profanity at the high dosage. The expectancy manipulation also produced an increase in self-reported aggression. Actual dosage and dosage expectancy did not influence assertiveness. PMID:6748671
Yamreudeewong, W; Johnson, J V; Cassidy, T G; Berg, J T
Warfarin is a commonly used oral anticoagulant that is usually initiated after the definitive diagnosis of a certain thromboembolic disorder or disease. Warfarin therapy will usually be prescribed for 6-12 weeks or more, and some patients may continue therapy throughout life, depending on the type of thromboembolic disorder. Major problems associated with warfarin therapy include adverse effects such as bleeding complications and drug-drug or drug-food interactions. In addition, thromboembolic complications may occur due to subtherapeutic dosages of warfarin. The laboratory reference standards for monitoring warfarin therapy are the prothrombin time (PT) and the International Normalized Ratio (INR). While both the PT or INR will reflect the clinical response in the patient, results reported as INR values have been shown to be more accurate than those reported as PT values. Thirty-two patients were enrolled in this study. Our objectives were to compare INR values measured by both the Coumatrak and conventional laboratory method, and to demonstrate the effects of pharmacist intervention on managing patients receiving warfarin therapy. Results from our study reveal that INR monitoring by Coumatrak is similar to the conventional laboratory method. In addition, our study indicates that patients receiving warfarin therapy can be monitored and managed effectively by pharmacists. PMID:8947990
Stormorken, H; Gjemdal, T; Bjøro, K
Lupus anticoagulants (LA) are associated with various forms of thrombotic events. Of particular interest to obstetrics is the association with placental infarcts and habitual abortion. In the case described a near full-term viable infant was delivered subsequent to four early miscarriages. However, the mother had then developed an antifactor II antibody leading to grave hypoprothrombinemia with bleeding tendency, indicating efficient autoanticoagulation. This natural experiment indicates that these patients should receive anticoagulation during pregnancy, possibly in combination with steroids to depress the LA level. PMID:3139508
Maiada M Almousilly
Full Text Available Phenytoin sodium was formulated in a solid dosage form using different bases; o/w emulsion base, water soluble base, oleaginous base, and vanishing cream base. Bases were prepared in two different concentrations, 5% and 10% w/w. The diffusion of the drug from each of the above bases was investigated. Results indicated that the effect of the type of ointment base on the release rate of phenytoin sodium is significant. The rate and extent of phenytoin sodium release and diffusion through mouse skin was higher from the water soluble base (10% w/w compared to other ointment bases, the difference was highly significant (P< 0.05.
Maiada M Almousilly; Loay K. Abdulrahman; Sadiq H. Alshmesawy; Fatima A. Tawfiq
Phenytoin sodium was formulated in a solid dosage form using different bases; o/w emulsion base, water soluble base, oleaginous base, and vanishing cream base. Bases were prepared in two different concentrations, 5% and 10% w/w. The diffusion of the drug from each of the above bases was investigated. Results indicated that the effect of the type of ointment base on the release rate of phenytoin sodium is significant. The rate and extent of phenytoin sodium release and diffusion through mouse ...
Rees, P; Grech, V
The insertion of a mechanical heart valve predisposes to thrombosis and embolism, and for this reason, individuals with mechanical valves who undergo dental/surgical procedures must take special precautions. In this article, we illustrate a protocol for anticoagulation during such procedures in individuals with mechanical valves. PMID:22368581
Feher, G; Illes, Z; Hargroves, D; Komoly, S
INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare form of venous thromboembolism (VTE). Although anticoagulation is recommended for the initial and long term treatment with regards to thrombotic risks for patients with CVT, the role of anticogalution has not been fully elucidated. The aim of...
Allione, Alessandra; Di Gaetano, Cornelia; Dani, Nadia; Barberio, Davide; Sieri, Sabina; Krogh, Vittorio; Matullo, Giuseppe
Obesity is an important health problem worldwide. Adipose tissue acts as an endocrine organ that secretes various bioactive substances, called adipokines, including pro-inflammatory biomarkers such as TNF-α, IL-6, leptin and C-reactive protein (CRP) and anti-inflammatory molecules such as adiponectin. The deregulated production of adipokines in obesity is linked to the pathogenesis of various disease processes and monitoring their variation is critical to understand metabolic diseases. The aim of this study was to determine the plasma concentration of adipokines in healthy subjects by multiplexed measurements and the effect of anticoagulants on their levels. Plasma samples from 10 healthy donors were collected in two different anticoagulants (sodium citrate or heparin). All markers, excluding TNF-α, showed significantly higher concentrations in heparinized compared to citrate plasma. However, levels of adipokines in different plasma samples were highly correlated for most of these markers. We reported that different anticoagulants used in the preparation of the plasma samples affected the measurements of some adipokines. The importance of the present results in epidemiology is relevant when comparing different studies in which blood samples were collected with different anticoagulants. PMID:26945995
Bobek, M.; Boubelík, Michael; Fišerová, Anna; Luptovcová, Martina; Vannucci, Luca; Kacprzak, G.; Kolodzej, J.; Majewski, A.M.; Hoffman, R. M.
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
Becattini, Cecilia; Agnelli, Giancarlo
Venous thromboembolism (VTE) is a common disease associated with high risk for recurrences, death, and late sequelae, accounting for substantial health care costs. Anticoagulant agents are the mainstay of treatment for deep vein thrombosis and pulmonary embolism. The recent availability of oral anticoagulant agents that can be administered in fixed doses, without laboratory monitoring and dose adjustment, is a landmark change in the treatment of VTE. In Phase III trials, rivaroxaban, apixaban, edoxaban (antifactor Xa agents), and dabigatran (an antithrombin agent) were noninferior and probably safer than conventional anticoagulation therapy (low-molecular-weight heparin followed by vitamin K antagonists). These favorable results were confirmed in specific patient subgroups, such as the elderly and fragile. However, some patients, such as those with cancer or with intermediate- to high-risk pulmonary embolism, were underrepresented in the Phase III trials. Further clinical research is required before new oral anticoagulant agents can be considered standard of care for the full spectrum of patients with VTE. PMID:27102510
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.)
PAVÃO MAURO S. G.
Full Text Available Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but with differences in the degree and position of sulfation were previously isolated from the body of the ascidian Styela plicata and Ascidia nigra. These differences produce profound effects on their anticoagulant properties. S. plicata dermatan sulfate composed by 2-O-sulfatedalpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N-acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75% and alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (25% disaccharide units has an anticoagulant activity 10 times lower than the mammalian heparin, is about 20 times less potent in the inhibition of thrombin by antithrombin, but has the same heparin cofactor II activity as mammalian heparin.
Sara Nicole Fernández
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.
Fernández, Sara Nicole; Santiago, Maria José; López-Herce, Jesús; García, Miriam; Del Castillo, Jimena; Alcaraz, Andrés José; Bellón, Jose María
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. PMID:25157369
Rombouts, Eva Karolien
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
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)
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.
Verheugt Freek WA
Full Text Available Abstract Thrombosis plays a major role in acute vessel closure both after coronary balloon angioplasty and after stenting. This review will address the role of antiplatelet and anticoagulant therapy in preventing early thrombotic complications after percutaneous coronary intervention. The focus will be on agents that are routinely available and commonly used.
Eerenberg, E.S.; Kamphuisen, P.W.; Sijpkens, M.K.; Meijers, J.C.; Büller, H.R.; Levi, M.
Background: Rivaroxaban and dabigatran are new oral anticoagulants that both have been licensed worldwide for the treatment of atrial fibrillation and rivaroxaban also for venous thrombosis. Both drugs specifically inhibit one coagulation factor, factor Xa and thrombin, respectively, and both compou
Grech, Victor E.; Rees, P.
The insertion of a mechanical heart valve predisposes to thrombosis and embolism, and for this reason, individuals with mechanical valves who undergo dental/surgical procedures must take special precautions. In this article, we illustrate a protocol for anticoagulation during such procedures in individuals with mechanical valves.
Middleberg, Robert A; Homan, Joseph
Rodenticide anticoagulants are used in the control of rodent populations. In addition to accidental ingestions in humans, such agents have also been used for homicidal and suicidal purposes. There are two major groups of rodenticide anticoagulants - hydroxycoumarins and indanediones. Before the advent of LC-MS/MS, analysis for such agents was relegated to such techniques as TLC and HPLC with nonspecific modes of detection. LC-MS/MS has been used to determine any given number of rodenticide anticoagulants in animal tissues, foods, plasma, etc. Use of this technique allows for the simultaneous identification of individual compounds within both classes of rodenticide anticoagulants. The LC-MS/MS method presented allows for simultaneous qualitative identification of brodifacoum, bromadiolone, chlorphacinone, dicumarol, difenacoum, diphacinone, and warfarin in blood, serum, and plasma using ESI in the negative mode. Two transitions are monitored for each analyte after a simple sample preparation. Chromatographic separation is accomplished using a gradient of ammonium hydroxide in water and ammonium hydroxide in methanol. Chloro-warfarin is used as internal standard. PMID:22767114
Jespersen, Stine Funder; Christensen, Louisa M; Christensen, Anders;
Background. The knowledge is still sparse about patient related factors, influencing oral anticoagulation therapy (OAC) rates, in stroke patients with atrial fibrillation (AF). Aims. To assess the use of OAC in ischemic stroke patients diagnosed with AF and to identify patient related factors...
Coumarin derivatives such as acenocoumarol, phenprocoumon and warfarin are frequently used for the prevention of stroke and systemic embolism in patients with atrial fibrillation or for the treatment of venous thromboembolism. These oral anticoagulants have a narrow therapeutic range and a large var
Waller, E S
Indomethacin, an indole derivative nonsteroidal anti-inflammatory drug, has been available since the early 1960s in gelatin capsules. In 1982, a sustained release product, Indocin SR, was marketed. Awaiting marketing approval is a unique controlled release form of indomethacin, Indos. The disposition of indomethacin includes enterohepatic cycling and extensive metabolism to inactive metabolites. Enterohepatic cycling makes interpretation of bioavailability estimates of indomethacin dosage forms difficult. The relationship of indomethacin plasma concentration to therapeutic effects and side effects is inconclusive. It appears in vivo prostaglandin inhibition occurs at very low plasma concentrations that are achievable with all available dosage forms. Indocin SR is a sustained release capsule of indomethacin designed to deliver 25 mg of drug immediately and 50 mg gradually. Absolute bioavailability of the product is 80%. The plasma concentration-time curves do not show good sustained release characteristics; after four hours plasma concentrations resemble those seen with a single dose of regular capsule. The cost compared with Indocin is competitive. Indos is a zero-order release form of indomethacin. It is a unique drug delivery system that shows good controlled release characteristics. Bioavailability is 85%. Both Indocin SR and Indos are apparently therapeutically equivalent to indomethacin capsules. In elderly patients, Indos has been shown to be associated with fewer side effects than Indocin. Both Indocin SR and Indos have the advantage of once or twice daily dosing. PMID:6361702
Full Text Available Abstract Background Despite the high frequency with which adverse drug events (ADEs occur in outpatient settings, detailed information regarding these events remains limited. Anticoagulant drugs are associated with increased safety concerns and are commonly involved in outpatient ADEs. We therefore sought to evaluate ambulatory anticoagulation ADEs and the patient population in which they occurred within the Duke University Health System (Durham, NC, USA. Methods A retrospective chart review of ambulatory warfarin-related ADEs was conducted. An automated trigger surveillance system identified eligible events in ambulatory patients admitted with an International Normalized Ratio (INR >3 and administration of vitamin K. Event and patient characteristics were evaluated, and quality/process improvement strategies for ambulatory anticoagulation management are described. Results A total of 169 events in 167 patients were identified from December 1, 2006-June 30, 2008 and included in the study. A median supratherapeutic INR of 6.1 was noted, and roughly half of all events (52.1% were associated with a bleed. Nearly 74% of events resulted in a need for fresh frozen plasma; 64.8% of bleeds were classified as major. A total of 59.2% of events were at least partially responsible for hospital admission. Median patient age was 68 y (range 36-95 y with 24.9% initiating therapy within 3 months prior to the event. Of events with a prior documented patient visit (n = 157, 73.2% were seen at a Duke clinic or hospital within the previous month. Almost 80% of these patients had anticoagulation therapy addressed, but only 60.0% had a follow-up plan documented in the electronic note. Conclusions Ambulatory warfarin-related ADEs have significant patient and healthcare utilization consequences in the form of bleeding events and associated hospital admissions. Recommendations for improvement in anticoagulation management include use of information technology to assist
Charles H Greenberg
Full Text Available The mechanism for hemorrhage enlargement in the brain, a key determinant of patient outcome following hemorrhagic stroke, is unknown. We performed computer-based stochastic simulation of one proposed mechanism, in which hemorrhages grow in "domino" fashion via secondary shearing of neighboring vessel segments. Hemorrhages were simulated by creating an initial site of primary bleeding and an associated risk of secondary rupture at adjacent sites that decayed over time. Under particular combinations of parameters for likelihood of secondary rupture and time-dependent decay, a subset of lesions expanded, creating a bimodal distribution of microbleeds and macrobleeds. Systematic variation of the model to simulate anticoagulation yielded increases in both macrobleed occurrence (26.9%, 53.2%, and 70.0% of all hemorrhagic events under conditions simulating no, low-level, and high-level anticoagulation and final hemorrhage size (median volumes 111, 276, and 412 under the same three conditions, consistent with data from patients with anticoagulant-related brain hemorrhages. Reversal from simulated high-level anticoagulation to normal coagulation was able to reduce final hemorrhage size only if applied relatively early in the course of hemorrhage expansion. These findings suggest that a model based on a secondary shearing mechanism can account for some of the clinically observed properties of intracerebral hemorrhage, including the bimodal distribution of volumes and the enhanced hemorrhage growth seen with anticoagulation. Future iterations of this model may be useful for elucidating the effects of hemorrhage growth of factors related to secondary shearing (such as small vessel pathology or time-dependent decay (such as hemostatic agents.
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.
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.
Yinon, Yoav; Pauzner, Rachel; Dulitzky, Mordechai; Elizur, Shai E; Dor, Jehoshua; Shulman, Adrian
The objective of this study was to assess the safety of induction of ovulation and oocyte retrieval in patients at risk of thrombosis, necessitating treatment with anticoagulants. Twenty-four patients considered as high risk for a thromboembolic event underwent 73 IVF cycles and 68 oocyte retrieval procedures, and were treated concomitantly with anticoagulation therapy (low molecular weight heparin; LMWH). A subgroup of five patients considered at especially high risk for thrombosis was isolated. These patients were prepared for oocyte retrieval using a controlled spontaneous cycle. All these patients were programmed exclusively for surrogacy. Nineteen women underwent 49 cycles of ovulation induction with gonadotrophins. The average peak oestradiol concentration was 1791 +/- 1420 pg/ml with an average of 13.5 +/- 8.4 oocytes retrieved in each cycle. The five patients from the very high risk group underwent 24 cycles: the average peak oestradiol concentration was 163 +/- 98 pg/ml. In 18, an egg was retrieved and in 14, fertilization was achieved. No bleeding or thromboembolic complications were noted during treatment of both groups of patients. It is concluded that during induction of ovulation in patients at risk for thrombosis, the introduction of LMWH as a cycle protective treatment was not associated with any medical complication. The use of a controlled spontaneous cycle with LMWH is suggested in very high risk patients. PMID:16578908
Chen, Zhen-Xia; Oliver, Brian
X chromosome dosage compensation is required for male viability in Drosophila. Dosage compensation relative to autosomes is two-fold, but this is likely to be due to a combination of homeostatic gene-by-gene regulation and chromosome-wide regulation. We have baseline values for gene-by-gene dosage compensation on autosomes, but not for the X chromosome. Given the evolutionary history of sex chromosomes, these baseline values could differ. We used a series of deficiencies on the X and autosomes, along with mutations in the sex-determination gene transformer-2, to carefully measure the sex-independent X-chromosome response to gene dosage in adult heads by RNA sequencing. We observed modest and indistinguishable dosage compensation for both X chromosome and autosome genes, suggesting that the X chromosome is neither inherently more robust nor sensitive to dosage change. PMID:25850426
WANG Jing; ZHANG Quanbin; ZHANG Zhongshan; HOU Yun; ZHANG Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminariajaponica,an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT).The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content,sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong
Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.
Suzuki, Tatsuhiko; Endo, Jiro
This paper reveals the dosages of decoctions in Shanghanlun in relation of pills and powder formulations, and obtains following results. At the first examination of the system of weight, while Taohongjing shows three kinds of system of weight; [(1)1liang is equivalent to 14 g. (2) 1liang = 7 g (3) 1liang = 1.4 g], he describes the necessity of the corrective system of weight among the decoctions, the pills and the powder formulations. After Song dynasty, Zhusanfa, which is the method of preparing the decoction by placing powder ingredients of prescriptions in water and simmer, have been mainly adopted. In the term of Zhusanfa, although the whole quantities of prescriptions are written with the ancient weight unit, the notation of the dosage is indicated by the current weight unit, Qian. In Shanghanlun, since the dosage form seems to have been changed from the pills or the powders into the decoction, some of decoctions contain impractical dose for decoction. PMID:21796994
Mickley, Frank; Geigenmüller, Grit; Schinköthe, Claudia
Equal safety and efficacy of direct oral anticoagulants as compared to vitamin K antagonists have been shown in elderly and very old patients. The use of these seem to have certain advantages in this special patient cohort: higher drug safety, no need for lab monitoring, less drug-drug interactions and a lower rate of intracranial hemorrhages. However, more data is needed to quantify the exact bleeding risk for geriatric patients. Elderly patients suffer quite frequently from significant comorbidities, such as renal failure, dementia, vision loss etc., which might put them at higher risk to suffer from medication side effects, especially bleeding complications. Routine clinical examinations combined with monitoring of renal function are therefore of paramount importance. Regarding these precautions the use of the new oral anticoagulants in the elderly is hence quite justified and rising. PMID:26625228
Summers, Richard L; Sterling, Sarah A
Direct oral anticoagulants (DOACs) offer clinical advantages over warfarin, such as minimal medication and food interactions and fixed dosing without the need for routine monitoring of coagulation status. As with all anticoagulants, bleeding, either spontaneous or provoked, is the most common complication. The long-term use of these drugs is increasing, and there is a crucial need for emergency medicine service professionals to understand the optimal management of associated bleeding. This review aims to describe the indications and pharmacokinetics of available DOACs; to discuss the risk of bleeding; to provide a treatment algorithm to manage DOAC-associated emergency bleeding; and to discuss future directions in bleeding management, including the role of specific reversal agents, such as the recently approved idarucizumab for reversal of the direct thrombin inhibitor dabigatran. Because air medical personnel are increasingly likely to encounter patients receiving DOACs, it is important that they have an understanding of how to manage patients with emergent bleeding. PMID:27255877
Amara, Walid; Larsen, Torben B; Sciaraffia, Elena; Hernández Madrid, Antonio; Chen, Jian; Estner, Heidi; Todd, Derick; Bongiorni, Maria G; Potpara, Tatjana S; Dagres, Nikolaos; Sagnol, Pascal; Blomstrom-Lundqvist, Carina
The purpose of this European Heart Rhythm Association survey was to assess the attitude, level of education, and knowledge concerning oral anticoagulants (OACs) among patients with atrial fibrillation (AF) taking vitamin K antagonists (VKAs), non-VKA oral anticoagulants (NOACs) or antiplatelets. A...... total of 1147 patients with AF [mean age 66 ± 13 years, 529 (45%) women] from 8 selected European countries responded to this survey. The overall use of OACs and antiplatelets was 77 and 15.3%, respectively. Of the patients taking OACs, 67% were on VKAs, 33% on NOACs, and 17.9% on a combination of OACs...... and antiplatelets. Among patients on VKAs, 91% correctly stated the target international normalized ratio (INR) level. The proportion of patients on VKA medication who were aware that monthly INR monitoring was required for this treatment and the proportion of patients on NOAC who knew that renal...
Menapace, Laurel A; McCrae, Keith R; Khorana, Alok A
The impact of venous thromboembolism (VTE) in the cancer population remains substantial despite significant advances in detecting and treating thrombotic events. While there is extensive literature regarding predictors of first VTE event in cancer patients as well as a validated predictive score, less data exist regarding recurrent VTE in cancer cohorts and associated predictive variables. A similar paucity of data in regard to bleeding events in cancer patients receiving anticoagulation has been observed. This review article will highlight clinical risk factors as well as predictive biomarkers associated with recurrent VTE and bleeding in cancer patients receiving therapeutic anticoagulation. Predictive risk assessment models for cancer-associated recurrent VTE and bleeding are also discussed. PMID:27067987
Nilsson, Hanna; Grove, E; Larsen, Torben Bjerregaard;
endpoints: all-cause mortality, major thromboembolism and bleeding events, percentage of time within therapeutic International Normalized Ratio (INR) target range (TTR) and variance of the INR value. Patient data was obtained from two databases in the two centers, where all data had been prospectively......Self-management of oral anticoagulant therapy in two centers: 11.000 patient-years of follow-up H Nilsson1,2,3, EL Grove2, TB Larsen3, M Maegaard1, TD Christensen1 1Department of Cardiothoracic and Vascular Surgery & Institute of Clinical Medicine, Aarhus University Hospital, Aarhus; 2Department of...... registered. Results: Results are pending but baseline characteristics (age, gender, indication for anticoagulant therapy) and data on all-cause mortality, major thromboembolism and bleeding events, TTR, INR-variance will be presented at the meeting. Conclusions: We hope to find a good quality of treatment...
Cohen, I A; Hutchison, T A; Kirking, D M; Shue, M E
Medical records were retrospectively analyzed to evaluate the success of a pharmacist-managed Anticoagulation Surveillance Clinic (ASC). The 78 patients in group I were followed by the ASC. The 17 patients in Group II were followed by other Veterans Administration Medical Center clinics. Demographic characteristics, warfarin indication and potentially complicating conditions were comparable between the groups. Group I patients had shorter intervals between visits to the clinic than Group II patients. Although not statistically different compared to Group II, Group I patients had better prothrombin time control. Group I patients also had fewer complications per treatment year (6.9% vs 9.0%) and received fewer potentially interacting drugs. The ASC was at least as successful as the other clinics in managing patients on warfarin, and results compared very favorably to those reported in the literature for other anticoagulation clinics. PMID:4019790
Saeed, Wajeeha; Burke, James F; Mirrani, Ghazi; Sirinivasa, Minisha; Nabi, Usman; Hayat, Umar; Khan, Zubair; Sardar, Muhammad Rizwan
Atrial fibrillation (AF) is the most common arrhythmia and represents one-third of the arrhythmia-related hospital admissions in the developed countries. Embolic strokes associated with AF are more severe and disabling. Thromboembolic stroke prevention is a major goal in treatment of AF and Warfarin has successfully served this purpose for many years. Drug-drug interaction and regular monitoring with Warfarin pose a significant challenge where health care system has limited resources; and lack of a well-structured health system, hinders regular International Normalized Ratio (INR) monitoring. Novel oral anticoagulants (NOACs) have opened up a new exciting chapter in the field of anticoagulation in non-valvular atrial fibrillation (NVAF). This review discussed the landmark trials that led to the development of NOACs and explored the potentials of these new agents with simultaneous comparison of Warfarin. PMID:27504556
Dimova, Cena; Kovacevska, Ivona; Angelovska, Bistra
Aim of this study is to review the evidence of different therapy approach, to highlight the areas of major concern, and to suggest specific oral surgery treatment for patients on new oral anticoagulants. A Medline and an extensive hand search were performed on English-language publications beginning in 1971 till now. The pertinent literature and clinical protocols of hospital dentistry departments have been extensively reviewed, presented and discussed. Several evolving clinical practic...
Fontana, Pierre; Robert-Ebadi, Helia; Bounameaux, Henri; Boehlen, Françoise; Righini, Marc
In recent years, small oral compounds that specifically block activated coagulation factor X (FXa) or thrombin (FIIa) have become alternatives to the anticoagulants that had been used for several decades. As of today, these direct oral anticoagulants (DOACs) include dabigatran etexilate (thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (inhibitors of FXa). While there is no doubt that DOACs represent a major step forward in the management of patients with venous thromboembolic disease and atrial fibrillation, new challenges have arisen. They need to be addressed with the necessary pragmatism on the basis of evidence. Indeed, a better understanding of the management of these last-generation antithrombotics will favour safer use and increase confidence of the practitioner for the prescription of these drugs. The aim of this article is to present practical suggestions for the prescription and use of these drugs in everyday clinical practice, based on clinical experience and recently updated recommendations of the European Heart Rhythm Association and the American College of Chest Physicians among other scientific organisations. We address issues such as pharmacokinetics, dosing, side effects, limitations of use, drug interactions, switching from and to other anticoagulants, renal function, concomitant administration of antiplatelet agents and perioperative use. We also address the issue of monitoring and reversal, taking advantage of the most recent development in this latter area. Rather than being one additional set of recommendations, our narrative review aims at assisting the practicing physician in his or her daily handling of these novel anticoagulant compounds, based on frequently asked questions to the authors, a group of experienced specialists in the field who have, however, no commitment to issue guidelines. PMID:26964028
Walmsley, T. A.; George, P M; Fowler, R. T.
AIMS: To determine if the iron in EDTA anticoagulated plasma samples can be measured by colorimetric assays using Ferrozine. METHODS: Paired samples of serum and EDTA plasma were obtained from 24 patients and analysed by three commercial iron methods. The EDTA plasmas were also analysed using methods modified by the addition of zinc sulphate or with different concentrations of Ferrozine. The iron contamination of EDTA sample tubes was measured by atomic absorption spectroscopy. RESULTS: Two c...
Hughes, Stephen; Szeki, Iren; Nash, Michael J; Thachil, Jecko
There is an increasing awareness about the risks of arterial and venous thromboembolism (TE) in hospital patients and general public which has led to consideration of thrombosis prevention measures in earnest. Early recognition of the symptoms of TE disease has led to timely administration of antiplatelet and anticoagulant drugs, translating to better outcome in many of these patients. In this respect, patients with chronic kidney disease (CKD) represent a special group. They indeed represent...
Konrad Jarząbek; Dawid Bąkowski; Beata Wożakowska-Kapłon
Atrial fibrillation is associated with a few folds higher risk of stroke. Traditional vitamin K antagonists used in the prevention of stroke in patients with non-valvular atrial fibrillation are often not efficient enough due to their interactions with a broad range of substances including medicines or food ingridients and problems with monitoring the treatment. New oral anticoagulants pose an alternative for the vitamin K antagonists. They are equally efficient in the prevention of stroke, ...
Pollack, Charles V
Long-term oral anticoagulant (OAC) therapy is used for the treatment and prevention of thrombosis and thromboembolism. As OAC use is so widespread, emergency physicians are likely to encounter patients on anticoagulant therapy in the emergency department (ED) on a regular basis, either for the same reasons as the population in general or as a result of the increased bleeding risk that OAC use entails.The vitamin K antagonist warfarin has been the standard OAC for several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply 'NOACs') have become available for long-term use. Protocols for assessing and managing warfarin-treated patients in the ED are well established and include international normalised ratio (INR) testing, which helps guide patient management. However, the INR does not give an accurate evaluation of coagulation status with NOACs, and alternative tests are therefore needed for use in emergency settings. This paper discusses what information the INR provides for a patient taking warfarin and which coagulation tests can guide the physician when treating patients on one of the NOACs, as well as other differences in emergency anticoagulation management. PMID:25987596
Fucoidan (FC),an effective anticoagulant constituent extracted from brown algae,was introduced into silk fibroin (SF) for improving its blood compatibility.The SF and SF/FC blend films were characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR),X-ray photoelectron spectroscopy (XPS),scanning electron microscopy (SEM) and dynamic contact angle determinator (CA).The in vitro anticoagulant activities of the films were evaluated by activated partial thromboplastin time (APTT),thrombin time (TT) and prothrombin time (PT) measurements.The endothelial cell attachment and proliferation viability on the film were assessed by micropipette aspiration technique and MTT assay,respectively.The testing results indicated that the introduction of FC increased the roughness,hydrophilicity and sulfate component of the film surface without impeding the formation of β-sheet conformation in SF.More important,FC brought excellent anticoagulant activity and better endothelial cell affinity to SF.The SF/FC blend film was hopeful to be used as blood-contacting biomaterials.
Skelley, Jessica W; Kyle, Jeffrey A; Roberts, Rachel A
To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966-March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians. PMID:27102287
Jennifer A Martin
Full Text Available Adverse drug reactions, including severe patient bleeding, may occur following the administration of anticoagulant drugs. Bivalirudin is a synthetic anticoagulant drug sometimes employed as a substitute for heparin, a commonly used anticoagulant that can cause a condition called heparin-induced thrombocytopenia (HIT. Although bivalrudin has the advantage of not causing HIT, a major concern is lack of an antidote for this drug. In contrast, medical professionals can quickly reverse the effects of heparin using protamine. This report details the selection of an aptamer to bivalirudin that functions as an antidote in buffer. This was accomplished by immobilizing the drug on a monolithic column to partition binding sequences from nonbinding sequences using a low-pressure chromatography system and salt gradient elution. The elution profile of binding sequences was compared to that of a blank column (no drug, and fractions with a chromatographic difference were analyzed via real-time PCR (polymerase chain reaction and used for further selection. Sequences were identified by 454 sequencing and demonstrated low micromolar dissociation constants through fluorescence anisotropy after only two rounds of selection. One aptamer, JPB5, displayed a dose-dependent reduction of the clotting time in buffer, with a 20 µM aptamer achieving a nearly complete antidote effect. This work is expected to result in a superior safety profile for bivalirudin, resulting in enhanced patient care.
Krupa, Mariusz; Moskała, Marek; Składzień, Tomasz; Grzywna, Ewelina
In recent years in the Department of Neurotraumatology in Cracow it has been noticed the frequent connection between appearance of chronic subdural hematoma (CSDH) and treatment by anticoagulant medications. The aim of this study is to draw attention to the problem of insufficient control of anticoagulants consumption, especially by patients treated for cardiovascular system diseases that increases the risk of bleeding and CSDH development. The paper is based on data from questionnaires that was sent to patients with CSDH, cured in the Department of Neurotraumatology form 2004 to 2005. Analyzed was the group of 51 patients with chronic subdural hematoma; 37 individuals (72.5%) confirmed taking acetylsalicylic acid in the period of 3 months before admission to the Department, 9 (17.6%) patients answered that they were taking low-molecular weight heparin. One patient (1.9%) was taking chronically derivative of cumarin. The authors would inform that anticoagulant treatment might favour increase of chronic subdural hematoma incidence. It's especially important, because the average life expectancy has been prolonged in Poland and there are more people taking acetylsalicylic acid. This can be an epidemiological problem in future. PMID:20043584
Emre Kumral; Tuba Cerraho(g)lu (S)irin
Recent evidence is leading to the replacement of vitamin K antagonists,the efficacy of which in preventing stroke in patients with atrial fibrillation (AF) is well established,with better tolerated and more manageable new anticoagulant drugs,with a lower risk of intracranial bleeding,no clear interactions with food,fewer interactions with medications,and no need for frequent laboratory monitoring and dose adjustments.Among new anticoagulants,dabigatran etexilate is a direct,competitive inhibitor of thrombin.It was evaluated for patients with AF in the RE-LY trial,showing lower rates of stroke and systemic embolism at a dose of 150 mg twice daily with similar rates of major hemorrhage compared with warfarin; and non-inferiority compared with warfarin for the prevention of stroke and systemic embolism at a dose of 110 mg twice daily,with lower rates of major bleeding.Beside dabigatran,oral factor X a inhibitors are also emerging for the prevention of thromboembolic events in AF.Despite the obvious advantages of these new oral anticoagulants over vitamin K antagonists,further information is still needed on how to prioritize the patients deriving the greatest benefit from these novel agents on the basis of patient characteristics or drug pharmacokinetics.There is also a need for assessing their long-term efficacy and safety over decades in the real-world setting.
Julio Cesar Lazaro
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.
... 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....
... 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...
... 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...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amoxicillin oral dosage forms. 520.88 Section 520.88 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 § 520.88 Amoxicillin...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Tetracycline oral dosage forms. 520.2345 Section 520.2345 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Tetracycline oral dosage forms....
... 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....
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dithiazanine iodide oral dosage forms. 520.763 Section 520.763 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dithiazanine iodide oral dosage forms....
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dexamethasone oral dosage forms. 520.540 Section 520.540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dexamethasone oral dosage forms....
Full Text Available Lubrication plays a key role in successful manufacturing of pharmaceutical solid dosage forms; lubricants are essential ingredients in robust formulations to achieve this. Although many failures in pharmaceutical manufacturing operations are caused by issues related to lubrication, in general, lubricants do not gain adequate attention in the development of pharmaceutical formulations. In this paper, the fundamental background on lubrication is introduced, in which the relationships between lubrication and friction/adhesion forces are discussed. Then, the application of lubrication in the development of pharmaceutical products and manufacturing processes is discussed with an emphasis on magnesium stearate. In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and trihydrate and its powder characteristics on lubrication efficiency, as well as product and process performance is summarized. In addition, the impact of lubrication on the dynamics of compaction/compression processes and on the mechanical properties of compacts/tablets is presented. Furthermore, the online monitoring of magnesium stearate in a blending process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical ingredient (API with magnesium stearate and its reactive impurities is reviewed with examples from the literature illustrating the various reaction mechanisms involved.
Ezekowitz, Michael D; Spahr, Judy; Ghosh, Pradeepto; Corelli, Kathryn
Anticoagulation for stroke prevention in atrial fibrillation (AF) is effective. Pivotal trials RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE-AF TIMI 48 tested novel agents against warfarin (W). In RE-LY, an open-label trial, dabigatran 150 mg BID (D150) was superior (35%) and 110 mg BID (D110) was noninferior to W. D150 reduced ischemic strokes by 25% and intracerebral bleeds by 74%, but increased major GI bleeds by 0.5 % per year. In ROCKET AF, a double-blind study, rivaroxaban 20 mg daily, downtitrated to 15 mg daily (if CrCl was 80; weight, 1.5 mg) was superior for safety (31%), efficacy (21%), and all-cause mortality (11%). In ENGAGE-AF TIMI 48, edoxaban 60 mg once daily (30 mg once daily if CrCl 30-50 ml/min, weight <60 kg, or concomitant verapamil or quinidine) was noninferior to W for efficacy, but reduced major bleeding (20%). To translate clinical trials to practice, understanding the disease and each anticoagulant is essential. For all novel agents, rapid anticoagulation, absence of monitoring, and a short half-life differentiate them from W. Bleed rates were either noninferior or lower than for W, without an antidote. Patient compliance is critical. Knowledge of renal function is essential and maintaining patients on therapy is key. PMID:24880227
Parry, D; Bryan, S; Gee, K; Murray, E.; Fitzmaurice, D
BACKGROUND: The demand for anticoagulation management is increasing. This has led to care being provided in non-hospital settings. While clinical studies have similarly demonstrated good clinical care in these settings, it is still unclear as to which alternative is the most efficient. AIM: To determine the costs borne by patients when attending an anticoagulation management clinic in either primary or secondary care and to use this information to consider the cost-effectiveness of anticoagul...
Kozik-Jaromin, Justyna; Nier, Volker; Heemann, Uwe; Kreymann, Bernhard; Böhler, Joachim
Background. Regional citrate anticoagulation is a very effective anticoagulation method for haemodialysis. However, it is not widely used, primarily due to the risk of hypocalcaemia. We studied citrate and calcium kinetics to better understand safety aspects of this anticoagulation method. Methods. During 15 haemodialysis treatments with a calcium-free dialysis solution, citrate was infused pre-dialyser and calcium was substituted post-dialyser. Systemic and extracorporeal citrate and calcium...
E. A. Belikov; K. V. Davtyan; O. N. Tkacheva
Prevention of thromboembolic complications in patients with atrial fibrillation during catheter pulmonary veins isolation is discussed. This subject review is presented with special consideration to new anticoagulants.
Singer, D E
Nonrheumatic atrial fibrillation (AFib) is the most potent common risk factor for stroke, raising the risk of stroke 5-fold. Six randomized trials of anticoagulation in AFib consistently demonstrated a reduction in the risk of stroke by about two-thirds. In these trials, anticoagulation in AFib was quite safe. In contrast, randomized trials indicate that aspirin confers only a small reduction in risk of stroke, at best. Pooled data from the first set of randomized trials indicate that prior stroke, hypertension, diabetes, and increasing age are independent risk factors for future stroke with AFib. Individuals AFib increases greatly at INR levels AFib depend on maintaining the INR between 2.0-3.0. Cost-effectiveness studies indicate that anticoagulation for AFib is among the most efficient preventive interventions in adults. Importantly, the benefits of anticoagulation in AFib accrue immediately. The implications for managed care organizations are that anticoagulation for AFib should be encouraged in their covered populations, and that dedicated anticoagulation services should be developed to promote system-wide control of anticoagulation intensity. Quality measures would include the proportion of patients with AFib who are anticoagulated, and the percentage of time patients' INR levels are between 2.0-3.0. Managed care organizations can benefit from recent research on anticoagulation for AFib; they have a responsibility to support future research and development efforts. PMID:9525571
Dosage patents are one way to extend the market exclusivity of an approved drug beyond the lifetime of the patent that protects the drug as such. Dosage patents may help to compensate the applicant for the long period where the active pharmaceutical ingredient as such is already under patent prosecution, but not on the market yet, due to lengthy development and approval procedures. This situation erodes part of the time the drug is marketed under patent protection. Dosage patents filed at a later date can provide remedy for this problem. Examples of successful and unsuccesful attempts, and the reasons for the respective outcomes, are provided in this article. PMID:27115842
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.)
Votruba-Drzal, Elizabeth; Miller, Portia
This ambitious monograph tackles several important questions related to children's preschool experiences that have relevance for program and policy initiatives at the state and federal levels. The authors' approach is rigorous: they conduct parallel analyses across eight large and diverse studies of preschool children in center care and use meta-analysis to summarize patterns across studies. The study finds nonlinear associations between preschool quality and gains in language and literacy skills, with larger associations in higher versus lower quality classrooms. Results also show that domain-specific measures of preschool quality were more strongly related to children's development than global quality measures. The "dosage" of preschool was likewise important: more years in Head Start predicted larger vocabulary and literacy gains, whereas more time spent on instruction predicted greater literacy and math skills growth. In this commentary, we situate these findings in the broader literature addressing links between preschool experiences and children's development and discuss key takeaways for research, practice, and policy. PMID:27273510
Jacob A Udell
Full Text Available BACKGROUND: Survivors of anterior MI are at increased risk for stroke with predilection to form ventricular thrombus. Commonly patients are discharged on dual antiplatelet therapy. Given the frequency of early coronary reperfusion and risk of bleeding, it remains uncertain whether anticoagulation offers additional utility. We examined the effectiveness of anticoagulation therapy for the prevention of stroke after anterior MI. METHODS AND FINDINGS: We performed a population-based cohort analysis of 10,383 patients who survived hospitalization for an acute MI in Ontario, Canada from April 1, 1999 to March 31, 2001. The primary outcome was four-year ischemic stroke rates compared between anterior and non-anterior MI patients. Risk factors for stroke were assessed by multivariate Cox proportional-hazards analysis. Warfarin use was determined at discharge and followed for 90 days among a subset of patients aged 66 and older (n = 1483. Among the 10,383 patients studied, 2,942 patients survived hospitalization for an anterior MI and 20% were discharged on anticoagulation therapy. Within 4 years, 169 patients (5.7% were admitted with an ischemic stroke, half of which occurred within 1-year post-MI. There was no significant difference in stroke rate between anterior and non-anterior MI patients. The use of warfarin up to 90 days was not associated with stroke protection after anterior MI (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.37-1.26. The use of angiotensin-converting-enzyme inhibitors (HR, 0.65; 95% CI, 0.44-0.95 and beta-blockers (HR, 0.60; 95% CI, 0.41-0.87 were associated with a significant decrease in stroke risk. There was no significant difference in bleeding-related hospitalizations in patients who used warfarin for up to 90 days post-MI. CONCLUSION: Many practitioners still consider a large anterior-wall MI as high risk for potential LV thrombus formation and stroke. Among a cohort of elderly patients who survived an anterior
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: firstname.lastname@example.org; Razdan, Rahul S.; Gagliardi, Joseph A.; Chaddha, Shashi K.B. [St Vincent' s Medical Center, Bridgeport, CT (United States)
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.
Just, Søren Andreas; Nybo, Mads; Laustrup, Helle;
Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis......Inflammation is strongly associated with lupus anticoagulant positivity, indepentent of know autoimmune disease and recent venous or arterial thrombosis...
Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. The aim of this study was to determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular dis...
Sarojini, S.; R. Manavalanb
Over the past four decades, gastro retentive dosage forms have recently become a leading methodology in the field of site-specific orally administered controlled release drug delivery system.. Gastroretentive dosage forms have the potential to improve local therapy with an increase of short gastric residence time and unpredictable gastric emptying time and decrease the variation in bioavailability which is unobserved, in other commercially available preparations. With the advent to current sc...
PROOST, JH; MEIJER, DKF
The pharmacokinetic software package MW/Pharm offers an interactive, user-friendly program which gives rapid answers in clinical practice. It comprises a database with pharmacokinetic parameters of 180 drugs, a medication history database, and procedures for an individual drug dosage regimen calcula
Cappelleri, Gianluca; Fanelli, Andrea
The use of direct oral anticoagulants including apixaban, rivaroxaban, and dabigatran, which are approved for several therapeutic indications, can simplify perioperative and postoperative management of anticoagulation. Utilization of regional neuraxial anesthesia in patients receiving anticoagulants carries a relatively small risk of hematoma, the serious complications of which must be acknowledged. Given the extensive use of regional anesthesia in surgery and the increasing number of patients receiving direct oral anticoagulants, it is crucial to understand the current clinical data on the risk of hemorrhagic complications in this setting, particularly for anesthesiologists. We discuss current data, guideline recommendations, and best practice advice on effective management of the direct oral anticoagulants and regional anesthesia, including in specific clinical situations, such as patients undergoing major orthopedic surgery at high risk of a thromboembolic event, or patients with renal impairment at an increased risk of bleeding. PMID:27290980
Vinholt, Pernille J; Nybo, Mads
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, and...... several coagulation factor levels were decreased. However, VWF activity and antigen were normal when analyzed by other methods. Also, coagulation factor levels were normal if an aPTT reagent with low lupus anticoagulant sensitivity or a chromogenic method was applied. Altogether, the initial findings were...... because of lupus anticoagulant interference and in fact, the patient had normal VWF activity and coagulation status. Interference of lupus anticoagulant in clot-based assays is well known but has not previously been described in VWF assays. This is furthermore the first report in which lupus anticoagulant...
Zacharski, Leo R
Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms. PMID:27413710
Full Text Available In intrauterine life, hemostasis is maintained by the same components as in extrauterine life (blood platelets, coagulation and fibrinolysis systems, involvement of the vascular wall; in the fetus, however, these components show significant differences of a quantitative/qualitative nature. In the present study, we surveyed the literature on the coagulation system in the fetus. We focused on the velocity of development of the coagulation system, being reflected in the increased concentration of all procoagulants and anticoagulants (a rise from approximately 20% in the middle of pregnancy to about 60% or more in the period of labor; exceptions: factors V, VIII and XIII which in the labor period reach the adult level and screening test results (prothrombin time, aPTT - activated prothrombin time, and thrombin time. Reference values were given for the 19-38 weeks of pregnancy and the labor term. Biochemical features of fetal fibrinogen and PIVKA factors were also discussed. The role of activated protein C (APC in the maintenance of balance between procoagulants and anticoagulants was postulated as well as the role of APC in the formation of thrombin activatable fibrinolysis inhibitor (TAFI.
Numerous studies have shown that elements of coagulation reactions mediate tumor cell proliferation, motility (invasiveness), tissue remodeling and metastasis. Coagulation activation is virtually a universal feature of human malignancy that differs from the clotting response to injury in that it is self-perpetuating rather than self-attenuating. Coagulation activation participates in tumor matrix deposition and local inflammation, and predicts subsequent cancer risk and adverse cancer outcomes. Several clinical trials of anticoagulants have shown improved outcomes in small cell carcinoma of the lung (SCCL) that have been correlated with assembly on the tumor cells of an intact coagulation pathway. However, variable efficacy of anticoagulant therapy has raised doubts about the coagulation hypothesis. Recently, initiators of coagulation and fibrinolytic pathways have been identified that mediate tumor inception and progression. Notable among these is oxidative stress driven by iron-catalyzed reactive oxygen species that may be the basis for local coagulation activation, tumor matrix deposition, inflammation and aberrant properties characteristic of the malignant phenotype. Recognition of important biological characteristics of individual tumor types, disease stage, choice of standard therapy including chemotherapy and the iron status of the host may clarify mechanisms. All of these are subject to modification based on controlled clinical trial design. Further tests of the coagulation hypothesis may lead to novel, low cost and relatively non-toxic approaches to treatment of malignancy including lung cancer that contrast with certain current cancer treatment paradigms.
Stöllberger, Claudia; Finsterer, Josef
Dabigatran, rivaroxaban, and apixaban are the new oral anticoagulants (NOAC) which have been investigated in patients with atrial fibrillation (AF) for primary and secondary prevention of stroke and thromboembolism. In these trials NOAC had a similar efficacy and safety profile compared to traditional vitamin-K-antagonists such as warfarin. We advise caution in the use of NOAC in patients with stroke or cerebral hemorrhage because of the following reasons: 1) Patients with cerebral bleeding were excluded from the trials. 2) Stroke within 14 days and severe stroke within 6 months before screening were exclusion criteria in the trials investigating dabigatran and rivaroxaban. 3) There is no antidote for reversal and no reliable laboratory monitoring of the anticoagulant effect for emergency situations. 4) NOAC are either substrates of the P-glycoprotein (P-gp) or are metabolized by the cytochrome P450 (CYP) system, or both. Drug-drug interactions between NOAC and P-gp and CYP-affecting drugs are largely unknown. 5) Long-term effects of thrombin generation inhibition on the occurrence of infections, malignancies, dementia, and other diseases are unknown. Based on these considerations it is our opinion that studies of NOAC in patients with stroke compared with other prevention strategies, as well as more post marketing surveillance data, are required. PMID:23628464
Robben, J H; Mout, H C; Kuijpers, E A
The occurrence, the diagnosis, and the treatment of anticoagulant rodenticide poisoning in dogs in the Netherlands was evaluated by a survey among Dutch veterinarians carried out by the National Poisons Control Center (NPCC). The survey included information on 54 dogs, 32 being treated by veterinarians who consulted the NPCC and 22 that were admitted to the Utrecht University Clinic for Companion Animals (UUCCA). The poisons that were suspected were brodifacoum (n = 19), bromadiolone (n = 14), difenacoum (n = 8), difethialone (n = 6) and chlorophacinone (n = 1). In 6 dogs the identity of the poison was unknown. Of 31 dogs with hemorrhages, 2 died shortly after presentation to practitioners and 2 died shortly after admission to the UUCCA. Signs of bleeding occurred especially in poisoning by brodifacoum (n = 16). In all but one of the dogs without hemorrhages, the intake of poison had taken place within 24 hours before presentation. The method of treatment varied, with the induction of vomiting and the use of vitamin K mentioned most. The choice of therapy was determined by the length of time after intake of the poison, the clinical signs and whether or not an anticoagulant toxicosis was suspected at the time of the initial examination. These findings provide the basis for discussion of several aspects of diagnosis and treatment. PMID:9534772
Ciurus, Tomasz; Cichocka-Radwan, Anna
Introduction The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. Material and methods We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. Results The mean age of the patients was 68.8 ± 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 ± 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR ≥ 80% were included in the stable anticoagulation group (TTR ≥ 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). Conclusions The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients. PMID:26855650
Pauline E Jullien
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.
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.
Full Text Available Abstract Background In animals with heteromorphic sex chromosomes, dosage compensation of sex-chromosome genes is thought to be critical for species survival. Diverse molecular mechanisms have evolved to effectively balance the expressed dose of X-linked genes between XX and XY animals, and to balance expression of X and autosomal genes. Dosage compensation is not understood in birds, in which females (ZW and males (ZZ differ in the number of Z chromosomes. Results Using microarray analysis, we compared the male:female ratio of expression of sets of Z-linked and autosomal genes in two bird species, zebra finch and chicken, and in two mammalian species, mouse and human. Male:female ratios of expression were significantly higher for Z genes than for autosomal genes in several finch and chicken tissues. In contrast, in mouse and human the male:female ratio of expression of X-linked genes is quite similar to that of autosomal genes, indicating effective dosage compensation even in humans, in which a significant percentage of genes escape X-inactivation. Conclusion Birds represent an unprecedented case in which genes on one sex chromosome are expressed on average at constitutively higher levels in one sex compared with the other. Sex-chromosome dosage compensation is surprisingly ineffective in birds, suggesting that some genomes can do without effective sex-specific sex-chromosome dosage compensation mechanisms.
Elmeros, Morten; Christensen, Thomas Kjær; Lassen, Pia
Anticoagulant rodenticides are widely used to control rodent populations but they also pose a risk of secondary poisoning in non-target predators. Studies on anticoagulant rodenticide exposure of non-target species have mainly reported on frequency of occurrence. They have rarely analyzed variations in residue concentrations. We examine the occurrence and concentrations of five anticoagulant rodenticides in liver tissue from 61 stoats (Mustela erminea) and 69 weasels (Mustela nivalis) from Denmark. Anticoagulant rodenticides were detected in 97% of stoats and 95% of weasels. 79% of the animals had detectable levels of more than one substance. Difenacoum had the highest prevalence (82% in stoats and 88% in weasels) but bromadiolone was detected in the highest concentrations in both stoat (1.290 μg/g ww) and weasel (1.610 μg/g ww). Anticoagulant rodenticide concentrations were highest during autumn and winter and varied with sampling method. Anticoagulant rodenticide concentrations were higher in stoats and weasels with unknown cause of death than in specimens killed by physical trauma. There was a negative correlation between anticoagulant rodenticide concentrations and body condition. Our results suggest that chemical rodent control in Denmark results in an extensive exposure of non-target species and may adversely affect the fitness of some stoats and weasels. PMID:21477845
Full Text Available Abstract Background The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. Methods MEDLINE and EMBASE databases were searched to identify relevant original articles. Results Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Conclusions Parenteral
Full Text Available Thyroid storm is a life-threatening condition that occurs secondary to an uncontrolled hyperthyroid state. Atrial fibrillation is a cardiovascular complication occurring in up to 15% of patients experiencing thyroid storm, and if left untreated this condition could have up to a 25% mortality rate. Thyroid storm with stroke is a rare presentation. This case report details a left middle cerebral artery (MCA stroke with global aphasia and thyroid storm in a 53-year-old Hispanic male patient. Although uncommon, this combination has been reported in multiple case series. Although it is well documented that dysfunctional thyroid levels promote a hypercoagulable state, available guidelines from multiple entities are unclear on whether anticoagulation therapy is appropriate in this situation.
Carazo, Matthew; Berger, Jeffrey S; Reyentovich, Alex; Katz, Stuart D
Heart failure continues to be a leading cause of morbidity and mortality throughout the United States. The pathophysiology of heart failure involves the activation of complex neurohormonal pathways, many of which mediate not only hypertrophy and fibrosis within ventricular myocardium and interstitium, but also activation of platelets and alteration of vascular endothelium. Platelet activation and vascular endothelial dysfunction may contribute to the observed increased risk of thromboembolic events in patients with chronic heart failure. However, current data from clinical trials do not support the routine use of chronic antiplatelet or oral anticoagulation therapy for ambulatory heart failure patients without other indications (atrial fibrillation and/or coronary artery disease) as the risk of bleeding seems to outweigh the potential benefit related to reduction in thromboembolic events. In this review, we consider the potential clinical utility of targeting specific pathophysiological mechanisms of platelet and vascular endothelial activation to guide clinical decision making in heart failure patients. PMID:26501990
Mamdani, M M; Racine, E; McCreadie, S; Zimmerman, C; O'Sullivan, T L; Jensen, G; Ragatzki, P; Stevenson, J G
We conducted a prospective cohort study to evaluate clinical and economic end points achieved by a pharmacist-managed anticoagulation service compared with usual care (50 patients/group). The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold. The primary economic end point was the direct variable cost of hospitalization from admission to discharge. No significant differences between groups were noted for the primary therapeutic end point. Total hospital costs were significantly lower for patients receiving pharmacist-managed care than for those receiving usual care ($1594 and $2014, respectively, 1997 dollars, p=0.04). Earlier start of warfarin (p=0.05) and shorter hospital stay (5 and 7 days, p=0.05) were associated with the pharmacist-managed group. PMID:10610013
Muschin, Tegshi; Budragchaa, Davaanyam; Kanamoto, Taisei; Nakashima, Hideki; Ichiyama, Koji; Yamamoto, Naoki; Shuqin, Han; Yoshida, Takashi
Naturally occurring galactomannans were sulfated to give sulfated galactomannans with degrees of substitution of 0.7-1.4 per sugar unit and molecular weights of M¯n=0.6×10(4)-2.4×10(4). Sulfated galactomannans were found to have specific biological activities in vitro such as anticoagulant, anti-HIV and anti-Dengue virus activities. The biological activities were compared with those of standard dextran and curdlan sulfates, which are polysaccharides with potent antiviral activity and low cytotoxicity. It was found that sulfated galactomannans had moderate to high anticoagulant activity, 13.4-36.6unit/mg, compared to that of dextran and curdlan sulfates, 22.7 and 10.0unit/mg, and high anti-HIV and anti-Dengue virus activities, 0.04-0.8μg/mL and 0.2-1.1μg/mL, compared to those curdlan sulfates, 0.1μg/mL, respectively. The cytotoxicity on MT-4 and LCC-MK2 cells was low. Surface plasmon resonance (SPR) of sulfated galactomannans revealed strong interaction with poly-l-lysine as a model compound of virus proteins, and suggested that the specific biological activities might originate in the electrostatic interaction of negatively charged sulfate groups of sulfated galactomannans and positively charged amino groups of surface proteins of viruses. These results suggest that sulfated galactomannans effectively prevented the infection of cells by viruses and the degree of substitution and molecular weights played important roles in the biological activities. PMID:27154517
WANG Jian-qi; SHI Xu-bo; YANG Jin-gang; HU Da-yi
Background Although low-molecular-weight heparin has replaced unfractionated heparin to become the primary anticoagulation drug for treatment of acute coronary syndrome, there is no convenient bedside monitoring method. We explored the best laboratory monitoring method of low-molecular-weight heparins (enoxapadn, dalteparin, and nadroparin) by use of the Sonoclot coagulation analyzer to monitor the activated clotting time.Methods Atotal of 20 healthy volunteers were selected and 15 ml of fasting venous blood samples were collected and incubated. Four coagulants, kaolin, diatomite, glass bead, and magnetic stick, were used to determine the activated clotting time of the low-molecular-weight heparins at different in vitro anti-Xa factor concentrations. A correlation analysis was made to obtain the regression equation. The activated clotting time of the different low-molecular-weight heparins with the same anti-Xa factor concentration was monitored when the coagulant glass beads were applied. Results The activated clotting time measured using the glass beads, diatomite, kaolin, and magnetic stick showed a linear correlation with the concentration of nadroparin (r= 0.964, 0.966, 0.970, and 0.947, respectively). The regression equation showed that the linear slopes of different coagulants were significantly different (glass beads 230.03 s/IU,diatomite 89.91 s/IU, kaolin 50.87 s/IU, magnetic stick could not be calculated). When the concentration of the anti-Xa factor was the same for different low-molecular-weight heparins, the measured activated clotting time was different after the application of the glass bead coagulant.Conclusions The glass bead coagulant is most feasible for monitoring the in vitro anticoagulation activity of nadroparin.The different effects of different low-molecular-weight heparins on the activated clotting time may be related to the different anti-Ila activities.
Wilke, Thomas; Groth, Antje; Pfannkuche, Matthias;
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...... have been recommended for 56.1/62.9 % of the patients (regarding factors disfavouring VKA/NOAC use). For 38.88/39.20 % of the patient-days in 2010 we could not observe any coverage by anticoagulants. Dementia of patients (OR 2.656) and general prescription patterns of the treating physician (OR 1...
Rahmat, Nur A; Lip, Gregory Y H
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...... major challenges: the need for reliable laboratory assays to assess their anticoagulation effect, and the lack of approved antidotes to reverse their action. This article provides an overview of monitoring the anticoagulant effect of NOACs and their potential specific antidotes in development....
Full Text Available The Curve Fitting and Interpolation Model are applied in Nonel dosage detection in this paper firstly, and the gray of continuous explosive in the Nonel has been forecasted. Although the traditional infrared equipment establishes the relationship of explosive dosage and light intensity, but the forecast accuracy is very low. Therefore, gray prediction models based on curve fitting and interpolation are framed separately, and the deviations from the different models are compared. Simultaneously, combining on the sample library features, the cubic polynomial fitting curve of the higher precision is used to predict grays, and 5mg-28mg Nonel gray values are calculated by MATLAB. Through the predictive values, the dosage detection operations are simplified, and the defect missing rate of the Nonel are reduced. Finally, the quality of Nonel is improved.
Parikh Vikas C.
Full Text Available A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of Gemfibrozil in bulk and pharmaceutical tablet dosage formulation. This method obeys Beer’s law in the concentration range of 30-90 µg/ml. with correlation coefficient of 0.9993 and exhibiting maximum absorption at 276 nm with apparent molar absorptivity of 0.1703 × 104 L mole-1 cm-1. The method is accurate and precise and is extended to pharmaceutical tablet dosage forms and there was no interference from any common pharmaceutical additives and excipients. The results of analysis were validated statistically and by recovery studies.
Parikh Vikas C.; Karkhanis V.V
A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of Gemfibrozil in bulk and pharmaceutical tablet dosage formulation. This method obeys Beer’s law in the concentration range of 30-90 µg/ml. with correlation coefficient of 0.9993 and exhibiting maximum absorption at 276 nm with apparent molar absorptivity of 0.1703 × 104 L mole-1 cm-1. The method is accurate and precise and is extended to pharmaceutical tablet dosage forms and there was no ...
Straughn, A B; Cruze, C A; Meyer, M C
A pharmacokinetic slide rule to facilitate the computations based on relatively simple pharmacokinetic principles involved in the development of individualized drug dosage regimens is described. The calculations are based on the assumption that the body can be conceived as a one-compartment open model with drug elimination proceeding by apparent first-order kinetics. Examples are presented (1) to illustrate the clinical application of a slide rule to compute the time-course of drug in the body, (2) to calculate steady-state maximum and minimum levels, and accumulation during multiple dosage and (3) to estimate appropriate maintenance doses and intravenous infusion rates. PMID:842548
Full Text Available A simple, accurate, rapid, and sensitive visible spectrophotometric method has been developed for the determination of valdecoxib in pure and pharmaceutical dosage forms. The method is based on the reaction of valdecoxib with potassium permanganate to form a bluish green coloured chromogen with an absorption maximum at 610 nm. Beer′s law was obeyed in the range of 5-25 mg/ml. The proposed method has been successfully applied to the analysis of the bulk drug and its dosage forms
Alessandro Morotti; Mauro Felice Frascisco
Life-threatening bleeding in anticoagulation with Warfarin is an emergency challenging issue. Several approaches are available to treat bleeding in either over-anticoagulation or proper-anticoagulation, 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 avai...
Full Text Available Intraoral hematoma secondary to systemic anticoagulant therapy is rare, but it is a potentially fatal condition requiring immediate medical management. Case report: Here we report a case of self-inflicted hematoma in the anterior maxillary gingival region in a 65year old female cardiac patient who was on systemic anticoagulant therapy with a poor periodontal condition, manifesting as a periodontal swelling for a period of one week. Oral anticoagulant therapy is considerably imperative to prevent thromboembolic complications in various medical conditions, in such patients there are chances for spontaneous bleeding or hematoma by means of minor trauma due to sharp teeth or dental prosthesis in the mouth leading to life threatening complications such as partial or complete airway blockage. Therefore,directives about possible bleeding complications secondary to anticoagulant drugs in the oral cavity and the importance of maintaining oral health hygiene are necessary for the patient.
Heiberg, Ann-Charlotte; Leirs, Herwig; Siegismund, Hans Redlef
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...
Nielsen, Henriette Svarre; Christiansen, Ole Bjarne
BACKGROUND: Anticardiolipin antibodies (ACA) are found with increased prevalence in women with unexplained recurrent miscarriage (RM) but their impact on future pregnancy outcome in lupus anticoagulant (LAC) negative patients needs better quantification. METHODS: The impact of a repeatedly positive...
Werth, Sebastian; Breslin, Tomás; NiAinle, Fionnuala; Beyer-Westendorf, Jan
Modern direct-acting anticoagulants are rapidly replacing vitamin K antagonists (VKA) in the management of millions of patients worldwide who require anticoagulation. These drugs include agents that inhibit activated factor X (FXa) (such as apixaban and rivaroxaban) or thrombin (such as dabigatran), and are collectively known today as non-VKA oral anticoagulants (NOACs). Since bleeding is the most common and most dangerous side effect of long-term anticoagulation, and because NOACs have very different mechanisms of action and pharmacokinetics compared with VKA, physicians are naturally concerned about the lack of experience regarding frequency, management and outcome of NOAC-associated bleeding in daily care. This review appraises trial and registry (or "real-world") data pertaining to bleeding complications in patients taking NOACs and VKA and provides practical recommendations for the management of acute bleeding situations. PMID:25940651
Spivak, Inna E
Anticoagulation is an important strategy for the prevention of stroke associated with atrial fibrillation. Development of new oral agents has created a need to educate nurses to administer these medications and provide patient education. PMID:26306367
Felice, L J; Chalermchaikit, T; Murphy, M J
A sensitive liquid chromatographic method was developed for the analysis of 4-hydroxycoumarin anticoagulant rodenticides in blood serum. The method can simultaneously measure the serum levels of five anticoagulant rodenticides: brodifacoum, bromadiolone, coumatetralyl, difenacoum, and warfarin. Serum proteins are precipitated with acetonitrile and the supernatant is mixed with ethyl ether. The organic phase is separated, evaporated to dryness, and the residue subjected to chromatographic analysis. The anticoagulants are separated by reversed-phase gradient chromatography with fluorescence detection at an excitation wavelength of 318 nm and emission wavelength of 390 nm. Extraction efficiencies of 68.1 to 98.2% were obtained. The within-run precision (CV) ranged from 2.19 to 3.79% and the between-run precision (CV) from 3.72 to 9.57%. The anticoagulants can be quantitated at serum levels of 10 to 20 ng/mL. PMID:1943055
Fauconnet, V; Pouliquen, H; Pinault, L
A reversed-phase high-performance liquid chromatographic method was developed for the analysis of eight anticoagulant rodenticides in animal liver. Coumarinic anticoagulant rodenticides (brodifacoum, bromadiolone, coumachlor, coumatetralyl, difenacoum, and warfarin) were detected by using a gradient elution and a fluorimetric detection. Indanedione anticoagulant rodenticides (chlorophacinone and diphacinone) were detected by using an isocratic elution and an UV detection. Anticoagulants were extracted from liver with mixtures of acetone/diethylether and acetone/chloroform. Extracts were applied to solid-phase extraction cartridges. Linearity was checked over the concentration range 0.1-0.6 microgram/g. Relative standard deviations of within-run and between-run variability were all between 5.7 and 10.3%. Recoveries from spiked liver samples were between 51.7 (difenacoum) and 78.2% (warfarin). Limits of detection were between 0.01 (difenacoum and warfarin) and 0.11 microgram/g (chlorophacinone). PMID:9399124
Riva, Nicoletta; Ageno, Walter
Anticoagulant treatment can be currently instituted with two different classes of drugs: the vitamin K antagonists (VKAs) and the newer, "novel" or non-vitamin K antagonist oral anticoagulant drugs (NOACs). The NOACs have several practical advantages over VKAs, such as the rapid onset/offset of action, the lower potential for food and drug interactions, and the predictable anticoagulant response. However, the VKAs currently have a broader spectrum of indications, a standardized monitoring test, and established reversal strategies. The NOACs emerged as alternative options for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Nevertheless, there remain some populations for whom the VKAs remain the most appropriate anticoagulant drug. This article discusses the advantages and disadvantages of VKAs and NOACs. PMID:25703519
Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic).
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.
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.
Ami M Karkar
Full Text Available Thromboembolism continues to be a major concern in patients with mechanical heart valves, especially in those with unsatisfactory anticoagulation levels. The new On-X valve (On-X Life Technologies, Austin, TX, USA has been reported as having unique structural characteristics that offer lower thrombogenicity to the valve. We report a case where the patient received no or minimal systemic anticoagulation after placement of On-X mitral and aortic valves due to development of severe mucosal arterio-venous malformations yet did not show any evidence of thromboembolism. This case report reinforces the findings of recent studies that lower anticoagulation levels may be acceptable in patients with On-X valves and suggests this valve may be particularly useful in those in whom therapeutic levels of anticoagulation cannot be achieved due to increased risk of bleeding.
Conclusions: Within the range of total energy examined, there is a positive correlation between total energy used and amount of pressure reduction achieved at up to 3 years of follow-up. This may be useful in determining the optimal energy dosage for maximum effect for patients receiving SLT.
Škrabanja, Vida; Zajc, Natalija; Gojak, Urška; Vrečer, Franc
The present invention relates to a pharmaceutical formulation comprising aliskiren or a pharmaceutically acceptable salt thereof as the active ingredient, wherein the pharmaceutical formulation is present in a solid dosage form suitable for oral administration based on a granulate obtained by a hot-melt and solvent-free granulation process, and to a process for manufacturing a pharmaceutical formulation.
Vogt, M; Derendorf, H; Krämer, J; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S; Dressman, J B; Barends, D M
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 prednisolone are reviewed. Data on its solubility, oral absorption, and permeability are not totally conclusive, but strongl
Jantratid, E; Prakongpan, S; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Barends, D M
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 cimetidine are reviewed. According to the current Biopharmaceutics Classification System (BCS), cimetidine would be assigned
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
McDonald John F
Full Text Available Abstract Background Dosage compensation in Drosophila is the epigenetic process by which the expression of genes located on the single X-chromosome of males is elevated to equal the expression of X-linked genes in females where there are two copies of the X-chromosome. While epigenetic mechanisms are hypothesized to have evolved originally to silence transposable elements, a connection between transposable elements and the evolution of dosage compensation has yet to be demonstrated. Results We show that transcription of the Drosophila melanogaster copia LTR (long terminal repeat retrotransposon is significantly down regulated when in the hemizygous state. DNA digestion and chromatin immunoprecipitation (ChIP analyses demonstrate that this down regulation is associated with changes in chromatin structure mediated by the histone acetyltransferase, MOF. MOF has previously been shown to play a central role in the Drosophila dosage compensation complex by binding to the hemizygous X-chromosome in males. Conclusion Our results are consistent with the hypothesis that MOF originally functioned to silence retrotransposons and, over evolutionary time, was co-opted to play an essential role in dosage compensation in Drosophila.
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a supplemental new animal...
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new...
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal...
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original abbreviated new...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... starting line). The loss on drying is not more than 10 percent when dried in vacuum at 60 °C for 2 hours....
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal...
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect the original approval of a new...
... HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of an original new animal...
Jansa, Petr; Homolka, David; Blatný, Radek; Mistrik, M.; Bartek, Jiří; Forejt, Jiří
Roč. 90, č. 6 (2014), 124/1-124/9. ISSN 0006-3363 R&D Projects: GA ČR GA13-08078S Institutional support: RVO:68378050 Keywords : gene dosage * male sterility * segmental trisomy * meiotic silencing of unsynapsed chromatin * DOWN-SYNDROME * MAMMALIAN MEIOSIS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.318, year: 2014
Hosmane, Sharath R.; Tucker, Johanna; Osman, Dave; Williams, Steve; Waterworth, Paul
Background Warfarin prescription for anticoagulation after cardiac surgery has always been a challenge for junior medical staff. Methods A prospective study was carried out to assess the quality of anticoagulation control by junior doctors compared with clinical pharmacists at South Manchester University hospitals NHS Trust. The junior medical staff prescribed warfarin for 50 consecutive patients from April to September 2006 (group A, n = 50) and experienced clinical pharmacists dosed 46 cons...
Dimova, Cena; Kovacevska, Ivona; Angelovska, Bistra
During the past 20 years, the approval of anticoagulants such as low-molecular-weight heparins (LMWHs), indirect factor Xa inhibitors and direct thrombin inhibitors has signaled a growing interest in antithrombotic compounds that have relatively discrete targets within the coagulation pathway. Aim of this study is to review the evidence of different therapy approach, to highlight the areas of major concern, and to suggest specific oral surgery treatment for patients on new oral anticoagul...
Luca Masotti; Mario Di Napoli; Walter Ageno; Davide Imberti; Cecilia Becattini; Maurizio Paciaroni; Daniel Augustin Godoy; Roberto Cappelli; Giancarlo Landini; Grazia Panigada; Ido Iori; Domenico Prisco; Giancarlo Agnelli
The patients with non-valvular atrial fibrillation (NVAF), both permanent and paroxysmal, and history of previous transient ischemic attack (TIA) or stroke represent a category of patients at high risk of new embolic events, independently of the presence of other risk factors. In these patients, national and international guidelines recommend oral anticoagulants as first choice for antithrombotic prevention. Direct oral anticoagulants (DOACs) have been demonstrated to be not inferior to warfa...
Hanninen, Mikael; Cassagneau, Romain; Manlucu, Jaimie; Yee, Raymond
Lead extraction is becoming increasingly common as indications for pacing and ICD insertion expand. Periop management varies between extraction centers, and no clinical guidelines have addressed the need for perioperative anticoagulation. We report a case of massive thrombosis which occurred shortly after laser lead extraction and is undoubtedly related to the trauma of the extraction and ensuing hypercoagulabiilty. Routine post-operative anticoagulation has been advocated as a means to preve...
Bergen, P. F. van; Deckers, J.W.; Jonker, J. J.; van Domburg, R. T.; Azar, A J; Hofman, A.
OBJECTIVE--To investigate the efficacy of long term oral anticoagulant treatment in subgroups of patients after myocardial infarction. DESIGN--Analysis of the effect of anticoagulant treatment in subgroups of hospital survivors of myocardial infarction based upon age, gender, history of hypertension, previous myocardial infarction, smoking habits, diabetes mellitus, Killip class, anterior location of infarction, thrombolytic therapy, and use of beta blockers. SUBJECTS--Participants of a multi...
Mankee, Anil; Petri, Michelle; Magder, Laurence S.
Introduction 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. Me...
Cappello, M; Vlasuk, G P; Bergum, P W; Huang, S.; Hotez, P. J.
Human hookworm infection is a major cause of gastrointestinal blood loss and iron deficiency anemia, affecting up to one billion people in the developing world. These soil-transmitted helminths cause blood loss during attachment to the intestinal mucosa by lacerating capillaries and ingesting extravasated blood. We have isolated the major anticoagulant used by adult worms to facilitate feeding and exacerbate intestinal blood loss. This 8.7-kDa peptide, named the Ancylostoma caninum anticoagul...
A. A. Rumyantsev; I. A. Pokataev; T.V. Kozlov; N.A. Rumyantsev
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 patien...
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 cha...
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 particul...
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
Acute mesenteric venous thrombosis is potentially lethal because it can result in mesenteric ischemia and, ultimately, bowel infarction requiring surgical intervention. Systemic anticoagulation for the prevention of thrombus propagation is a well-recognized treatment modality and the current mainstay therapy for patients with acute mesenteric venous thrombosis. However, the decision between prompt surgical exploration vs conservative treatment with anticoagulation is somewhat difficult in pat...
OBJECTIVE: Atrial fibrillation (AF) substantially increases risk of stroke. Evidence suggests that anticoagulation to reduce risk is underused (a "care gap"). Our objectives were to clarify measures of this gap in care by including data from family physicians and to determine why eligible patients were not receiving anticoagulation therapy. DESIGN: Telephone survey of family physicians regarding specific patients in their practices. SETTING: Nova Scotia. PARTICIPANTS: Ambulatory AF patients n...
Drozd, N N; Kuznetsova, S A; Kalinina, T B; Vasilieva, N Yu
Experiments on rabbits showed that increasing the dose of intravenously administered cellulose sulfate from wheat straw (dynamic viscosity 3.4 cP, sulfur content 14.1%) increased plasma clotting time in some coagulation tests and plasma anticoagulant activity. When cellulose sulfate was administered in the dose of 1 mg/kg, plasma clotting time in the presence of the anticoagulant (5 min after administration) was ~3-fold higher than after saline administration. PMID:27165079
Agnelli, Giancarlo; Becattini, Cecilia
The management of patients with acute pulmonary embolism is made challenging by its wide spectrum of clinical presentation and outcome, which is mainly related to patient haemodynamic status and right ventricular overload. Mechanical embolic obstruction and neurohumorally mediated pulmonary vasoconstriction are responsible for right ventricular overload. The pathophysiology of acute pulmonary embolism is the basis for risk stratification of patients as being at high, intermediate and low risk of adverse outcomes. This risk stratification has been advocated to tailor clinical management according to the severity of pulmonary embolism. Anticoagulation is the mainstay of the treatment of acute pulmonary embolism. New direct oral anticoagulants, which are easier to use than conventional anticoagulants, have been compared with conventional anticoagulation in five randomised clinical trials including >11 000 patients with pulmonary embolism. Patients at high risk of pulmonary embolism (those with haemodynamic compromise) were excluded from these studies. Direct oral anticoagulants have been shown to be as effective and at least as safe as conventional anticoagulation in patients with pulmonary embolism without haemodynamic compromise, who are the majority of patients with this disease. Whether these agents are appropriate for the acute-phase treatment of patients at intermediate-high risk pulmonary embolism (those with both right ventricle dysfunction and injury) regardless of any risk stratification remains undefined. PMID:25700388
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.
Ofosu, F A; Modi, G J; Blajchman, M A; Buchanan, M R; Johnson, E A
Heparan sulphate and dermatan sulphate have both antithrombotic and anticoagulant properties. These are, however, significantly weaker than those of a comparable amount of standard pig mucosal heparin. Antithrombotic and anticoagulant effects of glycosaminoglycans depend on their ability to catalyse the inhibition of thrombin and/or to inhibit the activation of prothrombin. Since heparan sulphate and dermatan sulphate are less sulphated than unfractionated heparin, we investigated whether the decreased sulphation contributes to the lower antithrombotic and anticoagulant activities compared with standard heparin. To do this, we compared the anticoagulant activities of heparan sulphate and dermatan sulphate with those of their derivatives resulphated in vitro. The ratio of sulphate to carboxylate in these resulphated heparan sulphate and dermatan sulphate derivatives was approximately twice that of the parent compounds and similar to that of standard heparin. Anticoagulant effects were assessed by determining (a) the catalytic effects of each glycosaminoglycan on the inhibition of thrombin added to plasma, and (b) the ability of each glycosaminoglycan to inhibit the activation of 125I-prothrombin in plasma. The least sulphated glycosaminoglycans were least able to catalyse the inhibition of thrombin added to plasma and to inhibit the activation of prothrombin. Furthermore, increasing the degree of sulphation improved the catalytic effects of glycosaminoglycans on the inhibition of thrombin by heparin cofactor II in plasma. The degree of sulphation therefore appears to be an important functional property that contributes significantly to the anticoagulant effects of the two glycosaminoglycans. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2963622
Gómez-Canela, Cristian; Barata, Carlos; Lacorte, Silvia
Anticoagulants are biocides widely used as pest control agents in agriculture, urban infrastructures, and domestic applications for the control of rodents. Other anticoagulants such as warfarin and acenocoumarol are also used as drugs against thrombosis. After use, anticoagulants are discharged to sewage grids and enter wastewater treatment plants (WWTPs). Our hypothesis is that WWTP effluents can be a source of anticoagulants to receiving waters and that these can affect aquatic organisms and other nontarget species. Therefore, the objective of the present study was to determine the occurrence of 11 anticoagulants in WWTPs receiving urban and agricultural wastewaters. Warfarin was the most ubiquitous compound detected in influent waters and was partially eliminated during the activated sludge treatment, and low nanograms per liter concentration were found in the effluents. Other detected compounds were coumatetralyl, ferulenol, acenocoumarol, flocoumafen, brodifacoum, bromadiolone, and difenacoum at concentrations of 0.86-87.0 ng L(-1). Considering water volumes of each WWTP, daily emissions were estimated to be 0.02 to 21.8 g day(-1), and thus, WWTPs contribute to the loads of anticoagulants to receiving waters. However, low aquatic toxicity was observed using Daphnia magna as a model aquatic organism. PMID:24622989
Full Text Available Anticoagulant therapy is essential for the prevention of risks associated with the formation of thrombus in patients after surgery, especially in orthopedics. Recently, new oral anticoagulants were introduced in the therapeutic arsenal. This fact is important, because the current drug of choice in clinical practice is enoxaparin, a low molecular weight heparin. As all injecting drugs, enoxaparin may reduce patients' adherence to treatment by dissatisfaction with and resistance to the administration. This article reviews the available literature on the overall utility of these innovative medicines, approaching the pharmacology, the compared efficacy in relation to current agents, and the potential targets for new agents, as well as points to new trends in research and development. The article also contributes with a practical guide for use and recommendations to health professionals, especially focusing on the reversibility of hemorrhagic events, and discusses the importance of convenience/satisfaction of use, the cost of treatment, and the risk-benefit profile for patients.A terapia anticoagulante é fundamental para a prevenção de riscos associados à formação de trombos em pacientes pós-cirúrgicos, principalmente em ortopedia. Recentemente, novos anticoagulantes orais foram introduzidos no arsenal terapêutico. Tal fato é importantíssimo, visto que o atual medicamento de primeira escolha na prática clínica é a enoxaparina, uma heparina de baixo peso molecular. Por ser de uso injetável, a enoxaparina pode diminuir a adesão do paciente ao tratamento, devido à insatisfação e à resistência quanto à via de administração. Este artigo revisa a literatura disponível sobre a utilidade total desses medicamentos inovadores ao abordar a farmacologia, a eficácia em comparação com os agentes atuais e os alvos potenciais para novos agentes, bem como aponta as novas tendências em pesquisa e desenvolvimento. O artigo também contribui
Paraish Misra, MD
Full Text Available Guidelines strongly recommend long-term anticoagulation with warfarin for patients with newly recognized AF who have high embolic risk by virtue of a CHADS2 (Congestive Heart Failure, Hypertension, Age >65, Diabetes, History of Stroke score ≥ 2. The goal of this study was to determine patterns of emergency department-initiated anticoagulation among eligible patients discharged from Canadian centers with an episode of recent-onset atrial fibrillation and flutter (RAFF and determine if decision-making is driven by the CHADS2 score or other factors. This was accomplished by examining health records using uniform case identification and data abstraction as well as centralized quality control; it was conducted in 8 Canadian university emergency departments over a 12-month period. Eligible patients for this analysis demonstrated RAFF requiring emergency management, were not already taking warfarin and were not admitted to hospital. Univariate analyses were conducted using T-test or Chi-square to select factors associated with anticoagulation initiation at a significance level of p < 0.15 and multiple logistic regression was employed to evaluate independent predictors after adjustment for confounders. Among 633 eligible patients, only 21 out of 120 patients (18% with a CHADS2 score ≥ 2 received anticoagulation and among 70 patients who were given anticoagulation only 21 (30% had a CHADS2 score ≥ 2. Independent predictors of anticoagulation included age by 10-year strata: (OR = 1.7; 95% CI 1.3 – 2.1, heparin use in the anticoagulation (OR = 9.6; 95% CI 4.9 – 18.9, a new prescription for metoprolol (OR = 9.6; 95% CI 4.9 – 18.9 and being referred to cardiology for follow-up (OR = 5.6; 95% CI 2.6 – 12.0. CHADS2 ≥ 2 doubled the likelihood of being prescribed anticoagulation (OR= 2.0; 95% CI 1.5 – 3.5 but was not an independent predictor. It was thus determined that patients discharged from the emergency department in this study were not
Full Text Available Piperlonguminine (PL, an important component of Piperlongum fruits, is known to exhibit anti-hyperlipidemic, antiplateletand anti-melanogenic activities. Here, the anticoagulantactivities of PL were examined by monitoring activatedpartial-thromboplastin-time (aPTT, prothrombin-time (PT, andthe activities of thrombin and activated factor X (FXa. Theeffects of PL on the expressions of plasminogen activatorinhibitor type 1 (PAI-1 and tissue-type plasminogen activator(t-PA were also tested in tumor necrosis factor-α (TNF-αactivated HUVECs. The results showed that PL prolonged aPTTand PT significantly and inhibited the activities of thrombin andFXa. PL inhibited the generation of thrombin and FXa inHUVECs. In accordance with these anticoagulant activities, PLprolonged in vivo bleeding time and inhibited TNF-α inducedPAI-1 production. Furthermore, PAI-1/t-PA ratio was significantlydecreased by PL. Collectively, our results suggest that PLpossesses antithrombotic activities and that the current studycould provide bases for the development of new anticoagulantagents. [BMB Reports 2013; 46(10: 484-489
Poposka, Lidija; Boskov, Vladimir; Risteski, Dejan; Taleski, Jane; Georgievska-Ismail, Ljubica
INTRODUCTION: In patients with an implanted pacemaker, asymptomatic atrial fibrillation (AF) is associated with an increased risk of thrombo-embolic complications. There is still no consensus which duration of episodes of atrial fibrillation should be taken as an indicator for inclusion of oral anticoagulation therapy (OAC). MATERIAL AND METHODS: A total of 104 patients who had no AF episodes in the past and have an indication for permanent pacing were included in the study. RESULTS: During an average follow-up of 18 months, 33 of the patients developed episodes of AF. Inclusion of OAC was performed in 17 patients, in whom AF was recorded, although in all patients CHA2DS2-VASc score was ≥ 1. The inclusion of OAC showed a statistically significant correlation with increasing duration of episodes of AF (r = 0.502, p = 0.003). During the follow-up period none of the patients developed thrombo-embolic complication. CONCLUSION: Considering that our group of patients had no thrombo-embolic events, we could conclude that dividing the AF episodes in less than 1% in 24 hours and longer than 1% within 24 hours could be an indicator for decision-making to include OAK if the CHA2DS2-VASc score is ≥ 1. PMID:27335594
Dr. J. David Spence
Full Text Available Patients in atrial fibrillation may have left atrial thrombi or strokes despite adequate anticoagulation. It is important to consider elevated plasma total homocysteine (tHcy as a treatable clotting factor that may explain such cases. Metabolic B12 deficiency is common even in patients with a “normal” serum B12. Measurement of holotranscobalamin, methylmalonic acid or, in folate-replete patients, tHcy are necessary to diagnose metabolic B12 deficiency when the serum B12 is below 400 pmol/L. Elevated tHcy quadruples the risk of stroke in atrial fibrillation, and is far more common than the usual clotting factors for which testing is commonly performed: among patients attending a secondary stroke prevention clinic, tHcy > 14 mmol/L is present in 20% at age 40, and in 40% at age 80. B vitamin therapy does reduce the risk of stroke; key issues are renal impairment and adequacy of vitamin B12. This intervention should be considered routinely in patients with AF.
Vitor Hugo Pomin
Full Text Available Marine sulfated polysaccharides (MSP, such as sulfated fucans (SF, sulfated galactans (SG and glycosaminoglycans (GAG isolated from either algae or invertebrate animals, are highly anionic polysaccharides capable of interacting with certain cationic proteins, such as (co-factors of the coagulation cascade during clotting-inhibition processes. These molecular complexes between MSP and coagulation-related proteins might, at first glance, be assumed to be driven mostly by electrostatic interactions. However, a systematic comparison using several novel sulfated polysaccharides composed of repetitive oligosaccharides with clear sulfation patterns has shown that these molecular interactions are regulated essentially by the stereochemistry of the glycans (which depends on a conjunction of anomericity, monosaccharide, conformational preference, and glycosylation and sulfation sites, rather than just a simple consequence of their negative charge density (mainly the number of sulfate groups. Here, we present an overview of the structure-function relationships of MSP, correlating their structures with their potential anticoagulant and antithrombotic actions, since pathologies related to the cardiovascular system are one of the major causes of illness and mortality in the world.
To evaluate the complications and outcome of anticoagulation therapy in pregnant females with valvular heart diseases. All pregnant females with prosthetic heart valves admitted in Armed Forces Institute of Cardiology from Jan 2004 to Dec 2004 were included in this study Basic demographic data including age, duration of pregnancy and complications observed were recorded. Warfarin was replaced with un-fractionated heparin (UFH) in first trimester and after that warfarin was continued with a targeted INR between 2.0-3.0. At 36 weeks warfarin was stopped and UFH was added; however, if patient went into spontaneous labour before this then immediate caesarian section was performed and UFH was restarted 4-6 hours after delivery along with oral warfarin. Out of 21 patients, sixteen (76.1%) had mitral valve diseases and five (23.9%) had both mitral and atrial. Majority (42.3%)of patients were in age group 26-30 years. Eleven (52.2%) reported in 9th month of gestation. Complications observed were hypertension (1), transient ischaemic attacks (1), pulmonary embolism (1), haemoptysis (1) and abortion (1). All patients, except one had successful completion of pregnancy. No case of foetal abnormality was seen. In 76% patients, daily dose of warfarin was <5 mg. Thrombo-prophylaxis in pregnancy with warfarin and UFH with an INR of 2.0-3.0 is effective in preventing thrombotic complications in females with mechanical valves without resulting in increase hemorrhagic complications. (author)
Bakalli, Aurora; Kamberi, Lulzim; Dragusha, Gani; Zeqiri, Nexhmi; Gashi, Fitim; Prekpalaj, Lazer
Background Despite the indisputable role of anticoagulation therapy for atrial fibrillation (AF) patients at risk for stroke, anticoagulants remain under-used in everyday clinical practice. We assumed that by performing trans-oesophageal echocardiography (TEE) on patients with AF who were not on anticoagulation treatment prior to the procedure, and by explaining to them the TEE images obtained, as well as the possible consequences of these findings, we could convince patients to start anticoa...
Tummala, Ramyashree; Kavtaradze, Ana; Gupta, Anjan; Ghosh, Raktim Kumar
The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Activated charcoal, hemodialysis, and activated Prothrombin Complex Concentrate (PCC) were amongst the nonspecific agents used in a DOAC associated bleeding but with limited success. Idarucizumab, the first novel antidote against direct thrombin inhibitor dabigatran was approved by US FDA in October 2015. It comprehensively reversed dabigatran-induced anticoagulation in a phase I study. A phase III trial on Idarucizumab also complete reversal of anticoagulant effect of dabigatran. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively. It is currently being studied in ANNEXA-4, a phase IV study. Aripazine (PER-977), the third reversal agent, has shown promising activity against dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH. This review article summarizes pharmacological characteristics of these novel antidotes, coagulation's tests affected, available clinical and preclinical data, and the need for phase III and IV studies. PMID:27082776
Wei Lai; Shi-Chun Lu; Guan-Yin Li; Chuan-Yun Li; Ju-Shan Wu; Qing-Liang Guo; Meng-Long Wang; Ning Li
AIM:To compare the incidence of early portal or splenic vein thrombosis (PSVT) in patients treated with irregular and regular anticoagulantion alter splenectomy with gastroesophageal devascularization.METHODS:We retrospectively analyzed 301 patients who underwent splenectomy with gastroesophageal devascularization for portal hypertension due to cirrhosis between April 2004 and July 2010.Patients were categorized into group A with irregular anticoagulation and group B with regular anticoagulation,respectively.Group A (153 patients) received anticoagulant monotherapy for an undesignated time period or with aspirin or warfarin without low-molecular-weight heparin (LMWH) irregularly.Group B (148 patients) received subcutaneous injection of LMWH routinely within the first 5 d after surgery,followed by oral warfarin and aspirin for one month regularly.The target prothrombin time/international normalized ratio (PT/INR) was 1.25-1.50.Platelet and PT/INR were monitored.Color Doppler imaging was performed to monitor PSVT as well as the effectiveness of thrombolytic therapy.RESULTS:The patients' data were collected and analyzed retrospectively.Among the patients,94 developed early postoperative mural PSVT,including 63patients in group A (63/153,41.17％) and 31 patients in group B (31/148,20.94％).There were 50 (32.67％)patients in group A and 27 (18.24％) in group B with mural PSVT in the main trunk of portal vein.After the administration of thrombolytic,anticoagulant and antiaggregation therapy,complete or partial thrombus dissolution achieved in 50 (79.37％) in group A and 26 (83.87％) in group B.CONCLUSION:Regular anticoagulation therapy can reduce the incidence of PSVT in patients who undergo splenectomy with gastroesophageal devascularization,and regular anticoagulant therapy is safer and more effective than irregular anticoagulant therapy.Early and timely thrombolytic therapy is imperative and feasible for the prevention of PSVT.
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.
Full Text Available Over the past four decades, gastro retentive dosage forms have recently become a leading methodology in the field of site-specific orally administered controlled release drug delivery system.. Gastroretentive dosage forms have the potential to improve local therapy with an increase of short gastric residence time and unpredictable gastric emptying time and decrease the variation in bioavailability which is unobserved, in other commercially available preparations. With the advent to current scientific and patented literature, this review have covered in detail the recent developments of FDDS including the physiological and formulation variables affecting gastric retention, classification, approaches to design single and multiple unit floating systems, formulation aspects and invitro and invivo studies to evaluate the performance.
Full Text Available Nateglinide (NTG is available as tablet dosage form in 60 mg and 120 mg strength. In the present study, two simple, reproducible and efficient UV spectrophotometric methods for the estimation of this drug in bulk and pharmaceutical dosage forms have been developed. In method I, methanol-AR was used as solvent, while in method II, Methanol-AR + 10% V/V 3N NaOH was used as reference solvent. In method I, nateglinide shows λmax at 216 nm, which is then shifted to 225.4 nm on increasing the basicity of the reference solvent in method II. The linearity for nateglinide was observed to be statistically in the range of 10-100 μg/ml in method I and 100-1000 μg/ml in method II. Both the methods were validated using ANOVA. The recovery studies confirmed the accuracy of the proposed methods.
Full Text Available In pharmaceutical organizations, validation is a fundamental segment that supports a company commitment to quality assurance. Validation is a tool of quality assurance which provides confirmation of the quality in equipment systems, manufacturing processes, software and testing methods. Validation assures that products with pre-determined quality characteristics and attributes can be reproduced consistently/reproducibly within the established limits of the manufacturing process operation at the manufacturing site. Validation of the individual steps of the manufacturing processes is called the process validation. Different dosage forms have different validation protocols. Here this article concentrates on the process validation of tablet dosage form, protocol preparation and regulatory basis for process validation in industry. It gives in detail the validation of each step of the manufacturing process of tablets through wet granulation.
Full Text Available A simple and sensitive spectrophotometric method has been developed for determination of azithromycin in its pharmaceutical dosage forms. In the proposed method, azithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone, in the presence of ammonium acetate. A yellow coloured chromogen was obtained, having an absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml, with regression coefficient of 0.9978. Various reaction parameters such as concentration of potassium permanganate and reagent, time required for oxidation, and maximum colour intensity were optimized. The method was validated, and can be used successfully to assay azithromycin in its pharmaceutical dosage forms viz. tablets, capsules, and injections.
Full Text Available A simple and sensitive spectrophotometric method has been developed for determination of roxithromycin in its pharmaceutical dosage forms. In the proposed method, roxithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone in the presence of ammonium acetate to give a yellow-coloured chromogen with absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml with regression coefficient of 0.9987. No significant difference was found between the proposed method and the reported method when two-tailed t-tests are applied. Various reaction parameters, such as concentration of potassium permanganate and reagent, time required for oxidation and maximum colour intensity, were optimized. The method was validated and can be used successfully to assay roxithromycin in its pharmaceutical dosage form, viz, tablets.
Huang, Haiyu; Zhao, Peisen; Chen, Pai-Yen; Ren, Yong; Liu, Xuewu; Ferrari, Mauro; Hu, Ye; Akinwande, Deji
Miniaturized helix antennas are integrated with drug reservoirs to function as RFID wireless tag sensors for real-time drug dosage monitoring. The general design procedure of this type of biomedical antenna sensors is proposed based on electromagnetic theory and finite element simulation. A cost effective fabrication process is utilized to encapsulate the antenna sensor within a biocompatible package layer using PDMS material, and at the same time form a drug storage or drug delivery unit inside the sensor. The in vitro experiment on two prototypes of antenna sensor-drug reservoir assembly have shown the ability to monitor the drug dosage by tracking antenna resonant frequency shift from 2.4-2.5-GHz ISM band with realized sensitivity of 1.27 [Formula: see text] for transdermal drug delivery monitoring and 2.76-[Formula: see text] sensitivity for implanted drug delivery monitoring. PMID:27170865
Kumar Vikash; Mishra Santosh Kumar; Lather Amit; Vikas; Singh Ranjit
Pellets have been used in the pharmaceutical industry for more than four decades, with the advent of controlled release technology, that the full impact of the inherent advantages of pellets over single unit dosage forms have been realized, not only has focused on refining and optimizing existing pelletization techniques, but also focused on the development of novel approaches and procedures for manufacturing of pellets. The present review outlines the manufacturing and evaluation of pellets....
Isabelle M Henry
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
C. K. Rameesa; M. K. Drisya
Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper p...
Perrin, A.; Musa, O. M.; STEED, J. W.
This review aims to introduce the chemistry of low dosage inhibitors of clathrate hydrate formation within the context of their role in the oil and gas industry. The review covers both kinetic hydrate inhibitors and anti-agglomerants from the point of view of structure–function relationships, focussing on recent refinements in mechanistic understanding and chemical design, and the consequently evolving and increasingly fine-tuned properties of these fascinating compounds.
Cooper, M K; Hamblen-Coyle, M. J.; Liu, X; Rutila, J E; Hall, J.C.
The period (per) gene is located on the X chromosome of Drosophila melanogaster. Its expression influences biological clocks in this fruit fly, including the one that subserves circadian rhythms of locomotor activity. Like most X-linked genes in Drosophila, per is under the regulatory control of gene dosage compensation. In this study, we assessed the activity of altered or augmented per(+) DNA fragments in transformants. Relative expression levels in male and female adults were inferred from...
To compare the radiation dosage and costs in conventional and digital technologies. The study dealt with transverse sections. The dosage applied with conventional technology was measured in 254 patients who intertwined 402 explorations of 6 anatomic regions in 4 Radiodiagnostic Services. The dosage applied with digital technology was measured in 57 patients who underwent 95 explorations of the same anatomic region in one Radiodiagnostic Service. The costs of the 6 types of conventional and digital explorations performed were calculated for two Radiodiagnostic Service. The doses administered (mGy) using convectional/digital technology were as follows: chest PA 0.2/0.1; chest LAT 0.7/0.3; breast CC 7.0/8.4; breast LAT 7.0/7.8; breast OB 7.0/10.5; cervical spine AP 9.6/9.0; cervical spine LAT 21.9/29.6; pelvis AP 7.3/7.1; plain abdominal 6.5/2.2. The costs incurred (1992 pesetas) with the convectional/digital technologies: chest AP and LAT 1,393/2,973; portable chest 2,027/3,714; mammography 2,357/3,486; phlebography 12,718/14,023; hysterosalpingography 4,876/6,701; bone scientigraphy 1,633/2,839. Compared with conventional technology, digital imaging reduces the radiation doses received by the patients, except in the case of mammography. The costs associated with the use of digital technology are greater than those incurred with conventional technology, mainly due to the costs of amortization. the use of digital technology is more justified when: 1) it is very necessary to reduce the dosage; 2) studies of chest and abdomen predominant; 3) the volume of utilization is high; 4) staff management is flexible , and 5) the cost of purchasing the equipment is lower. (Author) 10 refs
Suhagia B; Shah S; Rathod I; Patel H; Doshi K; Parmar V
A simple and sensitive spectrophotometric method has been developed for determination of roxithromycin in its pharmaceutical dosage forms. In the proposed method, roxithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone in the presence of ammonium acetate to give a yellow-coloured chromogen with absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml with regression...
Suhagia B; Shah S; Rathod I; Patel H; Doshi K
A simple and sensitive spectrophotometric method has been developed for determination of azithromycin in its pharmaceutical dosage forms. In the proposed method, azithromycin is oxidized with potassium permanganate to liberate formaldehyde, which is determined in situ using acetyl acetone, in the presence of ammonium acetate. A yellow coloured chromogen was obtained, having an absorption maxima at 412 nm. The method is found to be linear in the concentration range of 10-75 µg/ml, with ...
Petruševska, Marija; Berglez, Sandra; Krisch, Igor; Legen, Igor; Megušar, Klara; Peternel, Luka; Abrahamsson, Bertil; Cristofoletti, Rodrigo; Groot, D W; Kopp, Sabine; Langguth, Peter; Mehta, Mehul; Polli, James E; Shah, Vinod P; Dressman, Jennifer
Literature and experimental data relevant for the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing levetiracetam are reviewed. Data on solubility and permeability suggest that levetiracetam belongs to class I of the biopharmaceutical classification system (BCS). Levetiracetam's therapeutic use, its wide therapeutic index, and its favorable pharmacokinetic properties make levetiracetam a valid candidate for the BCS-based biowaiver approach. Further, no BE studies with levetiracetam IR formulations in which the test formulation failed to show BE with the comparator have been reported in the open literature. On the basis of the overall evidence, it appears unlikely that a BCS-based biowaiver approach for levetiracetam IR solid oral dosage forms formulated with established excipients would expose patients to undue risks. Thus, the BCS-based biowaiver approach procedure is recommended for IR solid oral dosage form containing levetiracetam, provided the excipients in the formulation are also present in products that have been approved in countries belonging to or associated with the International Committee on Harmonization and are used in their usual quantities, and provided the dissolution profiles of the test and reference product comply with the current requirements for BCS-based biowaivers. PMID:25663270
Thoracic radiographs and clinical records from 14 dogs with confirmed anticoagulant rodenticide toxicity were reviewed. Twelve of the 14 dogs were presented with a chief complaint of respiratory distress, and 12 had elevated prothrombin and activated partial thromboplastin times consistent with a coagulopathy secondary to a clotting factor deficiency. Thoracic radiographs of the 14 dogs were reviewed and abnomalities included increased mediastinal soft tissue opacity with extra and intrathoracic tracheal narrowing (4/14), increased mediastinal soft tissue opacity without tracheal narrowing (8/14), variable degrees of pleural effusion (13/14) and generalized, patchy interstitial/alveolar pulmonary infiltrates (8/14). Radiographic evidence of cardiomegaly and pulmonary artery abnormalities consistent with concurrent heartworm infestation were detected in one dog. In four dogs, dramatic tracheal narrowing was identified on the lateral thoracic radiograph caused by either mediastinal hemorrhage compressing the trachea or submucosal hemorrhage within the tracheal lumen. The trachea was displaced in a ventral direction in two dogs, and extra and intrathoracic luminal diameter narrowing was evident cranially in all four dogs. Two of these four dogs had soft tissue opacity within the dorsal trachea that extended from the larynx to the intrathoracic trachea. Twelve of the 14 dogs survived with standard treatment protocols utilizing injectable and oral vitamin K1. One dog died from pancreatitis and disseminated intravascular coagulopathy. The other dog died soon after presentation due to severe, disseminated hemorrhage. Follow-up thoracic radiographs were made in four dogs that survived and showed resolution of the mediastinal, pleural and pulmonary changes within one to five days after the initiation of vitamin K1 therapy
Başaran, Özcan; Dogan, Volkan; Beton, Osman; Tekinalp, Mehmet; Aykan, Ahmet Cağri; Kalaycioğlu, Ezgi; Bolat, Ismail; Taşar, Onur; Şafak, Özgen; Kalcik, Macit; Yaman, Mehmet; İnci, Sinan; Altintaş, Bernas; Kalkan, Sedat; Kirma, Cevat; Biteker, Murat
Abstract This study aimed to investigate the potential misuse of novel oral anticoagulants (NOACs) and the physicians’ adherence to current European guideline recommendations in real-world using a large dataset from Real-life Multicenter Survey Evaluating Stroke Prevention Strategies in Turkey (RAMSES Study). RAMSES study is a prospective, multicenter, nationwide registry (ClinicalTrials.gov identifier NCT02344901). In this subgroup analysis of RAMSES study, patients who were on NOACs were classified as appropriately treated (AT), undertreated (UT), and overtreated (OT) according to the European Society of Cardiology (ESC) guidelines. The independent predictors of UT and OT were determined by multivariate logistic regression. Of the 2086 eligible patients, 1247 (59.8%) received adequate treatment. However, off-label use was detected in 839 (40.2%) patients; 634 (30.4%) patients received UT and 205 (9.8%) received OT. Independent predictors of UT included >65 years of age, creatinine clearance ≥50 mL/min, urban living, existing dabigatran treatment, and HAS-BLED score of <3, whereas that of OT were creatinine clearance <50 mL/min, ongoing rivaroxaban treatment, and HAS-BLED score of ≥3. The suboptimal use of NOACs is common because of physicians’ poor compliance to the guideline recommendations in patients with nonvalvular atrial fibrillation (NVAF). Older patients who were on dabigatran treatment with good renal functions and low risk of bleeding were at risk of UT, whereas patients who were on rivaroxaban treatment with renal impairment and high risk of bleeding were at risk of OT. Therefore, a greater emphasis should be given to prescribe the recommended dose for the specified patients. PMID:27583892
Bernard, A; Fauchier, L; Pellegrin, C; Clementy, N; Saint Etienne, C; Banerjee, A; Naudin, D; Angoulvant, D
In patients with atrial fibrillation (AF) undergoing coronary stent implantation, the optimal antithrombotic strategy is unclear. We evaluated whether use of oral anticoagulation (OAC) was associated with any benefit in morbidity or mortality in patients with AF, high risk of thromboembolism (TE) (CHA2DS2-VASC score ≥ 2) and coronary stent implantation. Among 8,962 unselected patients with AF seen between 2000 and 2010, a total of 2,709 (30%) had coronary artery disease and 417/2,709 (15%) underwent stent implantation while having CHA2DS2-VASC score ≥ 2. During follow-up (median=650 days), all TE, bleeding episodes, and major adverse cardiac events (i.e. death, acute myocardial infarction, target lesion revascularisation) were recorded. At discharge, 97/417 patients (23%) received OAC, which was more likely to be prescribed in patients with permanent AF and in those treated for elective stent implantation. The incidence of outcome event rates was not significantly different in patients treated and those not treated with OAC. However, in multivariate analysis, the lack of OAC at discharge was independently associated with increased risk of death/stroke/systemic TE (relative risk [RR] =2.18, 95% confidence interval [CI] 1.02-4.67, p=0.04), with older age (RR =1.12, 1.04-1.20, p=0.003), heart failure (RR =3.26, 1.18-9.01, p=0.02), and history of stroke (RR =18.87, 3.11-111.11, p=0.001). In conclusion, in patients with AF and high thromboembolic risk after stent implantation, use of OAC was independently associated with decreased risk of subsequent death/stroke/systemic TE, suggesting that OAC should be systematically used in this patient population. PMID:23846210
Böttger, Björn; Thate-Waschke, Inga-Marion; Bauersachs, Rupert; Kohlmann, Thomas; Wilke, Thomas
Since the introduction of new oral anticoagulants (NOACs), besides vitamin-K antagonists, an additional option for stroke prevention of patients with atrial fibrillation (AF) is available. The objective of this study was to assess AF patients' preferences with regard to the attributes of these different treatment options. We conducted a multicenter study among randomly selected physicians. Preferences were assessed by computer-assisted telephone interviews. We used a discrete-choice-experiment (DCE) with four convenience-related treatment dependent attributes (need of bridging: yes/no, interactions with food/nutrition: yes/no, need of INR controls/dose adjustment: yes/no; frequency of intake: once/twice daily) and one comparator attribute (distance to practitioner: 15 km). Preferences measured in the interviews were analyzed descriptively and based on a conditional logit regression model. A total of 486 AF patients (age: 73.9 ± 8.2 years; 43.2 % female; mean CHA2DS2-VASc: 3.7 ± 1.6; current medication: 48.1 % rivaroxaban, 51.9 % VKA) could be interviewed. Regardless of type of medication, patients significantly preferred the attribute levels (in order of patients' importance) "once daily intake" (Level: once = 1 vs. twice = 0; Coefficient = 0.615; p 15 km = 0 vs. ≤1 km = 1; 0.494; p important OAC-attribute for patients' choice followed by "no bridging necessary" and "no interactions with food/nutrition". Thus, patients with AF seem to prefer treatment options which are easier to administer. PMID:26260625
Full Text Available The use of non-vitamin K antagonist oral anticoagulants (NOACs has become a breakthrough in anticoagulant treatment and it is expected to rise significantly in upcoming years. The use of conventional anticoagulants have several limitations: subcutaneous administration of heparin, or close monitoring of INR during application of vitamin K antagonists. In the last decade, target-specific oral anticoagulants (TSOAC including dabigatran, rivaroxaban, apixaban, edoxaban have been marketed for prophylaxis and treatment. Therefore, it is crucial to understand the potential uses, side effects, and management of these agents in routine practice. NOACs have major pharmacologic advantages, including a rapid onset and offset of action, fewer drug interactions than conventional anticoagulants, and predictable pharmacokinetics. These agents are gaining popularity among both physicians and patients because of their easiness of administration and the eliminating the requirement for regular coagulation monitoring. In this review, we focus on discussing practical recommendations for the use of NOACs and the risks and benefits of incorporating them into routine practice.
Full Text Available In order to search for sulfated polysaccharides in different invertebrate connective tissues and to examine their biological activities, we have isolated three types of polysaccharides from the body wall of the three sea cucumbers Holothuria edulis, Apostichopus japonicas and Holothuria nobilis. The physicochemical properties and anticoagulant activities of these polysaccharides were examined and compared. The chemical composition analysis and nuclear magnetic resonance (NMR analysis indicate that two types of polysaccharides, sulfated fucan and fucosylated chondroitin sulfate (FuCS, were found in all of the three species and in addition a neutral glycan was observed in H. edulis. The neutral α-glucan was firstly obtained from sea cucumber. The same type of polysaccharides from different species of sea cucumbers have similar physicochemical properties and anticoagulant activities, but those of different types of glycans are significantly different, possibly due to their different monosaccharide compositions, electric charges and average molecular weights. The FuCSs have stronger anticoagulant activities than the sulfated fucans, although the molecular sizes of the FuCSs are lower than those of the sulfated fucans, whereas the neutral glucan has no activity, as expected from the absence of sulfate. Thus, anticoagulant activities of the different type of polysaccharides are likely to relate to monosaccharide composition and sulfate content. Preliminary analysis suggests that the sulfation patterns of the FuCSs may result in the difference in anticoagulant activities. Our data could help elucidate the structure-activity relationship of the sea cucumber polysaccharides.
Menssen, H D; Melber, K; Brandt, N; Thiel, E
Undesirable interactions between anticoagulants and diagnostic test kit procedures so far have prevented the development of a single uniform blood sampling tube. Contrary to K2-EDTA, heparin and other anticoagulants, hirudin only minimally alters blood cells and dissolved blood constituents, thus qualifying as a universal anticoagulant for diagnostic purposes. Automated complete blood counts, automated analyses of clinical chemistry analytes and immunohaematology were performed from hirudinised and routinely processed blood obtained from healthy volunteers (n=35) and hospitalised patients (n=45). Hirudin (400 ATU/ml blood) sufficiently anticoagulated blood for diagnostic purposes. The measurements of automated complete blood counts obtained from K2-EDTA-anticoagulated and hirudinised blood correlated significantly as did the measurements of 24 clinical chemistry analytes from hirudinised plasma and serum. Regression analysis revealed that the results of complete blood counts and clinical chemistry tests were predictable from the respective measurements from hirudinised blood (p=0.001). Immunohaematological tests and cross-matching from hirudinised and native blood of the same donors gave identical results. Single clotting factors, but not global coagulation analytes, could be measured from hirudinised blood. Therefore, a universal hirudin-containing blood sampling tube could be designed for automated analysis of haematological, serological and clinical chemistry analytes. PMID:11798089
Romero Guardeño, Araceli; Pérez Lucena, Dolores Amalia
A significant increase during recent years in the number of patients who need Oral Anticoagulant Treatment has meant a greater role for nurses, especially in Primary Health Care Centers, since nurses, along with doctors, are the professionals responsible for treating those patients. This control is carried out by measuring the levels of anticoagulants in the blood, regulating the anticoagulant medicine doses, and providing patients with the essential health education so patients participate in the treatment of their illness. To a large degree, the preponderance of Primary Health Care Centers in the aforementioned control has developed hand-in-hand with the availability of portable, simple and low cost coagulation measuring systems which permit a direct reading of a patient's anticoagulation level with one drop of capillary blood. The objective of this article is introduce the reader to a measuring system appropriate for outpatient clinic control of anticoagulant levels in blood by mans of the CoaguChek XS System, which is described. The authors specify the sample extraction procedure, how to measure coagulant levels, and recommendations to keep in mind while carrying out this procedure. The authors sketch the importance of health education and finally, they describe some advantages and inconveniences this system has. PMID:19462604
Abdou, John K; Auyeung, Vivian; Patel, Jignesh P; Arya, Roopen
Adherence to medication, commonly reported as being 50% in chronic diseases, is of great concern in healthcare. Medication non-adherence is particularly apparent in chronic diseases, where treatment is often preventative and may provide little or no symptomatic relief or feedback for the patient. A lot of research has been undertaken to describe the extent of non-adherence to long-term anticoagulation therapy, particularly with vitamin K antagonists and more recently with direct oral anticoagulants. However, the literature is scarce with respect to describing adherence to anticoagulation in terms of the behavioural aspects that influence medicine use. Utilizing the COM-B (capability, opportunity, motivation and behaviour) psychological model of non-adherence, we present the available evidence, not only in terms of describing the extent of the non-adherence problem, but also describing why patients do not adhere, offering theory-driven and evidence-based solutions to improve long-term adherence to chronic anticoagulation therapy. Lessons learned are not only applicable within the field of anticoagulation but throughout haematology. PMID:27173746
Obamiro, Kehinde O; Chalmers, Leanne; Bereznicki, Luke R E
Atrial fibrillation (AF) is a growing public health concern and remains an independent risk factor for ischemic stroke. Warfarin, a commonly used oral anticoagulant, is associated with a 60-70 % relative reduction in stroke risk and a reduction in mortality of 26 %. However, warfarin has several limitations, including a narrow therapeutic window, variable dose response, multiple interactions with other drugs and concurrent illnesses, and the need for frequent laboratory monitoring. In recent years, the direct acting oral anticoagulants (DOACs), including dabigatran, rivaroxaban, apixaban and edoxaban, have been developed to overcome the limitations of warfarin therapy. These treatment strategies are either comparable or superior to warfarin in stroke prevention in AF. Despite the documented effectiveness of oral anticoagulants in AF, patients may not derive optimal benefit if they fail to adhere or fail to continue with their medication. This may lead to treatment failure, increased hospitalization and mortality. This review summarizes the literature regarding adherence and persistence (or discontinuation) rates with oral anticoagulants in the management of AF; the impact of non-adherence and non-persistence on treatment outcomes; and the effectiveness of strategies to improve adherence and persistence with oral anticoagulant therapy. PMID:27262433
Battinelli, Elisabeth M; Markens, Beth A; Kulenthirarajan, Rajesh A; Machlus, Kellie R; Flaumenhaft, Robert; Italiano, Joseph E
Platelets are a reservoir for angiogenic proteins that are secreted in a differentially regulated process. Because of the propensity for clotting, patients with malignancy are often anticoagulated with heparin products, which paradoxically offer a survival benefit by an unknown mechanism. We hypothesized that antithrombotic agents alter the release of angiogenesis regulatory proteins from platelets. Our data revealed that platelets exposed to heparins released significantly decreased vascular endothelial growth factor (VEGF) in response to adenosine 5'-diphosphate or tumor cells (MCF-7 cells) and exhibited a decreased angiogenic potential. The releasate from these platelets contained decreased proangiogenic proteins. The novel anticoagulant fondaparinux (Xa inhibitor) demonstrated a similar impact on the platelet angiogenic potential. Because these anticoagulants decrease thrombin generation, we hypothesized that they disrupt signaling through the platelet protease-activated receptor 1 (PAR1) receptor. Addition of PAR1 antagonists to platelets decreased VEGF release and angiogenic potential. Exposure to a PAR1 agonist in the presence of anticoagulants rescued the angiogenic potential. In vivo studies demonstrated that platelets from anticoagulated patients had decreased VEGF release and angiogenic potential. Our data suggest that the mechanism by which antithrombotic agents increase survival and decrease metastasis in cancer patients is through attenuation of platelet angiogenic potential. PMID:24065244
... 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 Food and Drugs 6 2010-04-01 2010-04-01 false Flumethasone implantation or injectable dosage... HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.960 Flumethasone implantation or injectable dosage forms....
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ampicillin implantation and injectible dosage... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.90 Ampicillin implantation and injectible dosage forms....
... 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....
Vitale, Gail A.
The purpose of this study was to examine how nursing efficacy for drug-dosage calculation instruction is determined. Medication administration is a critical function of nurses in healthcare settings. An essential component of safe medication administration is accurate drug-dosage calculation, but instruction in drug-dosage calculation methods…
A. P. Momot
Full Text Available The anticoagulants of indirect action during many years serve drugs of basic prophylaxis and therapy of thromboembolic episodes at cardiovascular , neurological, oncology, orthopaedic and other diseases, after surgical interventions and traumas, and also large bunch of the generically caused and acquired (secondary thrombophilie. The contents of vitamin К1 in nutrition depend on a method of product preparation. The highest concentrations are found in dark green vegetables and grass: parsley, spinach, green turnip, and also in cabbage and lettuce. For achievement stable hypocoagulation at assignment of anticoagulants of indirect action the daily entering with nutrition of constant amounts of vitamin K (at a level 65-80 mkg/day is necessary. Thus, a doctor at assignment of anticoagulants, is obliged to pay attention to character of a food and to inform patient about possible undesirable consequences at the use of products keeping high levels of vitamin К1.
Christensen, Thomas D; Attermann, Jørn; Hjortdal, Vibeke E.;
complications requiring doctoral intervention. All the patients and their parents expressed full satisfaction with the treatment. Conclusion: Selfmanagement of oral anticoagulation provides a good quality of treatment, which is feasible and safe in selected children with congenital cardiac disease.......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...
Heiberg, A.C.; Leirs, H.; Siegismund, Hans Redlef
how bromadiolone-resistant phenotypes are manifested when bromadiolone selection is absent. Experimental populations were established under semi-natural conditions with wild rats trapped at two Danish farms. The individuals caught on each of the two farms were divided into two experimental groups. One......Resistance to anticoagulant rodenticides in Norway rats (Rattus norvegicus) is documented to be associated with pleiotropic effects, notably with an increased dietary vitamin K requirement. The aim of this study was to quantify these effects in small populations of Norway rat in Denmark and to see...... against resistance in the two non-treatment populations was found to be insignificant. Thus, absence of anticoagulant, under the environmental conditions provided, did not lead to a selection favouring anticoagulant-sensitive rats. However, we found some evidence of selection against presumed homozygous...
Stabile, Eugenio; Izzo, Raffaele; Rozza, Francesco; Losi, Maria Angela; Coscioni, Enrico; Trimarco, Bruno
Vitamin K-dependent antagonists (VKAs) are the most commonly used oral anticoagulants. Non-VKA oral anticoagulants (NOACs), directly target factor IIa (dabigatran) or Xa (rivaroxaban, apixaban, and edoxaban) have predictable pharmacological effects and relatively few drug and food interactions compared with VKA. Among NOACs, dabigatran has been extensively tested for stroke prevention in patients with non-valvular atrial fibrillation eligible for oral anticoagulation with VKA. Dabigatran is at least as effective as warfarin at preventing stroke with advantages of less serious bleeding except for gastrointestinal bleeding, which occurs more often than with warfarin. The findings of dabigatran use in randomized trials, post market registries and specific clinical settings are discussed in this article. PMID:27207360
Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin
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. PMID:26358933
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 that...... showed in some patients being prescribed coumarin anticoagulants, especially warfarin, that the International Normalised Ratio (INR) increased after they began taking glucosamine, which indicated an increase in the coagulation time. In most cases the increased INR values were symptomless but in some...... 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...
Greaves, J H; Rehman, A B
Three South-Asian rodent past species were tested for susceptibility to anticoagulant rodenticides. Wheat fluor containing 0-025% warfarin 0-0375% coumatetralyl or 0-005% difenacoum was fed to 260 Tatera indica, 140 Nesokia indica and 81 Bandicota bengalensis for 1-56 days. Tatera was about as susceptible to anticoagulants as Rattus has been reported to be. Nesokia and Bandicota were extremely variable: though the majority were highly susceptible, the slopes of the dose-mortality curves were close to zero. The difenacoum diet appeared to be more toxic than the warfarin diet to all three species, but less toxic than the coumatetralyl diet to Tatera and Nesokia. All of the anticoagulants were eventually lethal to all of the animals tested. PMID:264500
Amartya Kundu; Partha Sardar; Jessica Huston; Parijat Sen; Saurav Chatterjee; Ramez Nairooz; John J. Ryan; Wilbert S. Aronow
Full Text Available Novel Oral Anticoagulants (NOACs such as Dabigatran, Rivaroxaban, Apixaban and Edoxaban are becoming increasingly popular choices for anticoagulation in place of oral Vitamin K Antagonists in various clinical settings. However, they are thought to be associated with an increased risk of gastrointestinal bleeding. Moreover, no specific antidote is available which can rapidly reverse the anti-coagulant action of NOACs raising concern that gastrointestinal bleeding with NOACs could carry a worse prognosis than that associated with conventional agents. In this review, we describe a case of gastrointestinal bleeding in the setting of NOAC use, followed by a brief overview of the pivotal trials involving NOACs. Clinical issues such as pathophysiology, diagnosis and management of NOAC induced GI bleeding have been described. Future trials will help elucidate the true incidence, risk factors and preventive strategies for NOAC associated gastrointestinal bleeding.
Martin, Karlyn; Key, Nigel S
Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we review atherothrombotic disease, venous thrombotic disease, and atrial fibrillation in patients with inherited bleeding disorders, and discuss strategies for using anticoagulants in this population using cases to illustrate these considerations. PMID:27106121
Albert, Nancy M
Atrial fibrillation (AF), a common arrhythmia, increases the risk of ischemic stroke. Stroke and bleeding scores for patients with AF can help to stratify risk and determine the need for antithrombotic therapy, for which warfarin has been the gold standard. Although highly effective, warfarin has several limitations that can lead to its underuse. Data from randomized, Phase III clinical trials of the novel oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban and apixaban, both factor Xa inhibitors, indicate these drugs are at least noninferior to warfarin for the prevention of stroke and systemic embolism. They are easier to administer, and have an equivalent or lower risk of bleeding versus warfarin. A better understanding of the risks and benefits of the novel oral anticoagulants, and their use in clinical practice, will prepare clinicians to anticipate and address educational and clinical needs of AF patients and their families, and promote evidence-based prescription of appropriate and safe anticoagulation therapy. PMID:24373340
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.
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 (owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian shorteared owl (Asio flammeus sandwichensis) and Hawaiian 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.
Markussen, Mette Drude Kjær; Heiberg, Ann-Charlotte; Fredholm, Merete;
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...
Mahmoud, W; Redfern, R
The response of Acomys cahirinus to three anticoagulant rodenticides was investigated in the laboratory. In contrast to the other commensal rodents Rattus rattus and R. norvegicus, this species appears to be naturally very resistant to warfarin, difenacoum and brodifacoum. It is considered unlikely that anticoagulant poisons would be effective in the field for the control of A. cahirinus. PMID:7240734
Taki Galanis, MD
Conclusions: These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE.
Markussen, Mette Drude; Heiberg, Ann-Charlotte; Fredholm, Merete;
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. W...
Full Text Available A case of rheumatic heart disease (RHD with prosthetic mitral valve endocarditis receiving anticoagulation with heparin, underwent medical termination of pregnancy in a second trimester. The following report entails the use of aminocaproic acid (ACA in preventing excessive bleeding during and after the procedure, while the patient continued to receive anticoagulant therapy.
Moore, Gary W; Culhane, Aidan P; Maloney, James C; Archer, Robert A; Breen, Karen A; Hunt, Beverley J
A study is presented which assesses the diagnostic impact of incorporating Taipan snake venom time (TSVT) with ecarin time confirmatory test into an existing dilute Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT) repertoire when testing nonanticoagulated patients for lupus anticoagulants. A total of 387 plasma samples from nonanticoagulated patients being investigated for antiphospholipid antibodies were tested for lupus anticoagulant by dRVVT and dilute APTT with confirmatory and mixing tests, and TSVT with ecarin time, with commercially available reagents. All were analyzed on a Sysmex CS2000i automated analyzer. Lupus anticoagulant was not detected by dRVVT, dilute APTT or TSVT screening in 265 of 387 (68.5%) samples. A lupus anticoagulant was detected in 60 (15.5%) samples in dRVVT and/or dilute APTT analysis, but gave normal TSVT ratios. Thirty-nine (10.1%) were positive by TSVT and ecarin time and one or both of dRVVT and dilute APTT testing, whereas a further 23 (5.9%) were only positive in TSVT/ecarin time testing. Most of the lupus anticoagulants manifested in dRVVT and/or APTT analysis, as might be anticipated for this reagent pairing. The samples positive by TSVT/ecarin time only, as has been previously demonstrated, emphasize that the many variables that impact lupus anticoagulant testing mean that even a well established dRVVT and APTT pairing cannot deliver diagnostic certainty. Interference by direct factor Xa inhibitors in dRVVT testing could pave the way for wider adoption of TSVT screening as we gain more evidence of its diagnostic performance. PMID:26656903
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.
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
Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials
Boutitie, Florent; Pinede, Laurent; Schulman, Sam; Agnelli, Giancarlo; Raskob, Gary; Julian, Jim; Hirsh, Jack; Kearon, Clive
Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the shortest length of anticoagulation that reduces the risk of recurrence to its lowest level. Design Pooled analysis of individual participants’ data from seven randomised trials. Setting Outpatient anticoagulant clinics in academic centres. Population 2925 men or women with a first venous thromboem...
Full Text Available As a result of sex chromosome differentiation from ancestral autosomes, male mammalian cells only contain one X chromosome. It has long been hypothesized that X-linked gene expression levels have become doubled in males to restore the original transcriptional output, and that the resulting X overexpression in females then drove the evolution of X inactivation (XCI. However, this model has never been directly tested and patterns and mechanisms of dosage compensation across different mammals and birds generally remain little understood. Here we trace the evolution of dosage compensation using extensive transcriptome data from males and females representing all major mammalian lineages and birds. Our analyses suggest that the X has become globally upregulated in marsupials, whereas we do not detect a global upregulation of this chromosome in placental mammals. However, we find that a subset of autosomal genes interacting with X-linked genes have become downregulated in placentals upon the emergence of sex chromosomes. Thus, different driving forces may underlie the evolution of XCI and the highly efficient equilibration of X expression levels between the sexes observed for both of these lineages. In the egg-laying monotremes and birds, which have partially homologous sex chromosome systems, partial upregulation of the X (Z in birds evolved but is largely restricted to the heterogametic sex, which provides an explanation for the partially sex-biased X (Z expression and lack of global inactivation mechanisms in these lineages. Our findings suggest that dosage reductions imposed by sex chromosome differentiation events in amniotes were resolved in strikingly different ways.
Full Text Available How allopolyploids are able not only to cope but profit from their condition is a question that remains elusive, but is of great importance within the context of successful allopolyploid evolution. One outstanding example of successful allopolyploidy is the endemic Iberian cyprinid Squalius alburnoides. Previously, based on the evaluation of a few genes, it was reported that the transcription levels between diploid and triploid S. alburnoides were similar. If this phenomenon occurs on a full genomic scale, a wide functional ''diploidization'' could be related to the success of these polyploids. We generated RNA-seq data from whole juvenile fish and from adult livers, to perform the first comparative quantitative transcriptomic analysis between diploid and triploid individuals of a vertebrate allopolyploid. Together with an assay to estimate relative expression per cell, it was possible to infer the relative sizes of transcriptomes. This showed that diploid and triploid S. alburnoides hybrids have similar liver transcriptome sizes. This in turn made it valid to directly compare the S. alburnoides RNA-seq transcript data sets and obtain a profile of dosage responses across the S. alburnoides transcriptome. We found that 64% of transcripts in juveniles' samples and 44% in liver samples differed less than twofold between diploid and triploid hybrids (similar expression. Yet, respectively 29% and 15% of transcripts presented accurate dosage compensation (PAA/PA expression ratio of 1 instead of 1.5. Therefore, an exact functional diploidization of the triploid genome does not occur, but a significant down regulation of gene expression in triploids was observed. However, for those genes with similar expression levels between diploids and triploids, expression is not globally strictly proportional to gene dosage nor is it set to a perfect diploid level. This quantitative expression flexibility may be a strong contributor to overcome the genomic shock
Full Text Available A 40 year s lady who underwent a mitral valve replacement with a mechancial prosthesis nine years ago, stopped oral anticoagulants totally. She was asymptomatic and doing her field job with good exercise tolerance for 4 years without any anticoagulation or follow - up and presented now with acute pulmonary edema due to prosthetic valve thrombosis. Echocardiography revealed a large clot on the mitral valve and increased Doppler gradients across the valve. She was given intravenous streptokinase for 28 hours with relief o f symptoms, re - appearance of prosthetic valve click and normalisation of flow velocities. She was prescribed oral acenocoumarol and discharged in a stable condition.
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
Gray, David R; Garabedian-Ruffalo, Susan M; Chretien, Steven D
A cost-benefit evaluation of a clinical pharmacist-managed anticoagulation clinic (AC) was performed. Outpatient and hospital records were examined for 26 patients in the treatment group with an AC clinic and 26 patients in the control group. Therapeutic prothrombin times were maintained within the treatment group to a significantly greater extent than within the control group (ppharmacist-managed AC was effective in maintaining therapeutic prothrombin times, and reducing the incidence of hospitalizations resulting from anticoagulation complications, and can be cost-justified based on a cost-benefit analysis. PMID:17341522
Penka, M; Buliková, A; Gumulec, J; Matýsková, M; Smejkal, P; Kissová, J; Slechtová, M; Chlupová, G
Coumarins belong to drugs widely used and the spectrum of their use is going to grow. From this point of view and/or because the coumarins are adminstrated in patients who are treated for the other diseases--medical or surgical--at the same time, it is necessary to modify, interrupt or replace peroral anticoagulant treatment in the dependence on various aspects. It requires to compound different algorithms for given situations solution. It is always to decide, if the situation is imperative from the view of solution planed, what risk brings proposed treatment and what is the risk of anticoagulant treatment modification. PMID:16637448
Pottegård, Anton; Meegaard, P. M.; Holck, L. H.;
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......). SUBJECTS: Both cases and controls were selected from users of VKA. Cases were defined by being hospitalised with a main diagnosis indicating excessive anticoagulation. For each case, we selected 15 controls among VKA users, matched by age and sex. MAIN OUTCOME MEASURE: Odds ratio for experiencing excessive...
Chery, Jessica; Larschan, Erica
Dosage compensation is the essential process that equalizes the dosage of X-linked genes between the sexes in heterogametic species. Because all of the genes along the length of a single chromosome are co-regulated, dosage compensation serves as a model system for understanding how domains of coordinate gene regulation are established. Dosage compensation has been best studied in mammals, flies and worms. Although dosage compensation systems are seemingly diverse across species, there are key shared principles of nucleation and spreading that are critical for accurate targeting of the dosage compensation complex to the X-chromosome(s). We will highlight the mechanisms by which long non-coding RNAs function together with DNA sequence elements to tether dosage compensation complexes to the X-chromosome. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. PMID:24406325
Full Text Available Topical application of drugs to the eye is most popular and well-accepted route of administration for the treatment of various eye disorders. A variety of ocular dosage form and drug delivery systems, including a controlled release of the drug, drug targeting, and penetration enhancement of the drug, have been investigated. Polymers have been widely used as the drug carrier for controlled-release systems. Polymers release the drug as they themselves degrade and are sometimes finally absorbed within the body. In this article, several ocular drug delivery systems have discussed using different kinds of polymers and their acceptance over conventional.
R.A. Ajadi; Adetunji, A.; V.O. Omoerah; J.U. Okoh
Three series of trials involving 10 domestic short-haired cats were carried out to determine the influence of dosage of contrast media or type of chemical restraint on feline excretory urography. The 1st series (group A) involved 5 cats sedated with 2.0 mg/kg intramuscular (i.m) injection of 2 % xylazine and receiving 800 mg/kg of 76 % meglumine diatrizoate (urografin). The 2nd series (group B) involved another 5 cats sedated with 2.0 mg/kg (i.m) injection of 2 % xylazine and receiving 1200 m...
临床药师参与抗凝管理服务对经皮球囊二尖瓣成形术后心房颤动患者华法林抗凝效果和安全性影响的随机对照试验%A randomized controlled trial of warfarin anti-coagulation efficacy and safety of clinical pharmacist-participated anticoagulation management for patients with atrial fibrillation after percutaneous balloon mitral valvuloplasty
李峥嵘; 王凌; 石增成; 鲍玉琳
(PBMV). Methods The patients who underwent PBMV were divided into trial group and control group by random number table. The patients in the trial group received the clinical pharmacist-participated AMS. The clinical pharmacist provided adjusted warfarin dosage suggestion to clinician and warfarin anticoagulant education to the patients and their family members. The patients in the control group received warfarin following the visiting doctor's advice. Anticoagulant effect indicators included international normalized ratio( INR)compliance rate,effective anticoagulation rate, anticoagulant deficiency rate and excessive anticoagulation rate. Safety evaluation indicators were embolism and bleeding events during the anticoagulant therapy. Results A total of 131 patients were enrolled in the study. The trial group comprised 68 and the control group 63 patients,respectively. The differences in the patients' age,sex composition,body weight,smoking and drinking habits,degree of mitral stenosis, combined disease,baseline INR,and preliminary warfarin dosage after PBMV were not significant between the 2 groups(all P > 0. 05). The INR compliance rate in the trial group and the control group were 53. 3%(217 / 407)and 41. 8%(155 / 371),respectively(P = 0. 001);effective anticoagulation rates were 55. 9%(38 / 68)and 33. 3%(21 / 63),respectively(P = 0. 016);anticoagulant deficiency rate were 19. 9%(81 /407)and 27. 8%(103 / 371),respectively( P = 0. 003);and the excessive anticoagulation rates were 7. 9%(32 / 407)and 14. 0%(52 / 371),respectively(P = 0. 006). There were 6 and 9 patients developed minor bleeding events and each was one slight embolism in the trial group and the control group, respectively. The incidence rate of adverse reactions in the trial group(10. 3% )was lower than that in the control group(15. 9% ),but the difference was not significant. Conclusion The clinical pharmacist-participated AMS may increase the INR compliance rate and the effective anticoagulation rate
Twelve groups of falcons, each containing three female gyrfalcon-peregrine falcon hybrids (Falco rusticolus x Falco peregrinus) were injected intramuscularly with a single dose of ivermectin ranging from 0.2 mg/kg to 11 mg/kg bodyweight, and a control group was injected with water. Doses of ivermectin between 0.2 and 5 mg/kg failed to produce clinical signs of illness in the birds. Four birds which received either 6, 7 or 8 mg/kg showed slight clinical signs, and all the birds receiving 9 to 11 mg/kg showed more or less severe clinical signs of anorexia, apathy and sedation. Slight changes in the mean plasma activities of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase (AP) were detected in the group dosed with 5 mg/kg, and higher dosages caused marked changes in these enzymes as well as in the mean plasma activity of lactate dehydrogenase. The mean activity of AP decreased, and the activities of the other enzymes increased. A dosage of 2 to 3 mg/kg ivermectin is recommended as a safe and effective antiparasitic drug for falcons and it has been used successfully to treat infestations of Serratospiculum species. PMID:11386446
Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel
The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry. PMID:27194002
C. K. Rameesa
Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.
Clemente-Ruiz, Marta; Murillo-Maldonado, Juan M; Benhra, Najate; Barrio, Lara; Pérez, Lidia; Quiroga, Gonzalo; Nebreda, Angel R; Milán, Marco
Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID:26859353
Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.)
Roldan, Tamara; Landzberg, Michael J; Deicicchi, David J; Atay, Julie K; Waxman, Aaron B
Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk. PMID:26527532
Full Text Available Background: Dried Whitmania pigra is used for the treatment of cardiovascular and cerebrovascular diseases in traditional Chinese medicine and hot water and alcohol extracts also have anticogulant activity. However, a lower molecular weight and more stable anticogulant is needed. Objective: The objective of the following study is to purify and characterize of an anticoagulant oligopeptide from Hirudo (Whitmania pigra Whitman. Materials and Methods: Gel filtration on Sephadex G 50, ion exchange on diethylaminoethyl cellulose, and semi prepared high performance liquid chromatography were used to purify Hirudo. Automated coagulation analyzer was used for evaluating anticoagulant activity. Molecular weight was measured by Matrix assisted laser desorption ionization time of flight mass spectrometry. Amino acid sequence of the oligopeptide was measured by amino acid sequence analyzer. Results: A new anticoagulant, named whitide, isolated from Hirudo was purified, with a molecular weight 1997.1 Da. Amino acid sequence of the oligopeptide was identified as Gly-Pro-ALa-Gly-Hyp-Val-Gly-Ala-Hyp-Gly-Gly-Hyp-Gly-Val-Arg-Gly-Leu-Hyp-Gly-Asp-Arg-Gly. The results revealed that its amino acid sequence had strong homology to various types of collagen. Conclusion: Whitide might be an orally anticoagulant for its hot and trypsin stable.
To determine the CT findings of an acute pulmonary thromboembolism for the prediction of response to anticoagulant therapy. Forty-eight patients diagnosed with a pulmonary embolism underwent anticoagulant therapy, and underwent pre- and post-treatment CT scans, were selected to be part of the study. Pre-treatment CT scans were retrospectively reviewed for the number and degree of emboli, right ventricular to left ventricular (RV/LV) diameter ratio, pulmonary arterial to aorta (PA/aorta) diameter ratio, ventricular septal bowing, consolidation, mosaic perfusion, and pleural effusion. The response to anticoagulant therapy was assessed by a change in embolic burden on pre-and post-treatment CT scans. The 48 patients were divided into two groups: good responder and poor responder. The pre-treatment CT findings were compared by group to determine if there were any differences in the CT findings. Thirty patients were categorized as good responders (62.5%) and eighteen patients as poor responders (37.5%). A pleura-based wedge-shaped consolidation was observed in 9 of 18 cases (50%) from the poor responder group and one of 30 (3%) cases from the good responder group. The comparison of the finding by group was found to be significantly different (p<0.001). No other CT findings were significantly different between the good and poor responders. The pre-treatment CT scans of patients with acute pulmonary embolism indicate that pleurabased wedge-shaped consolidations can predict a poor response to anticoagulant therapy
Swadzba, J.; Iwaniec, T.; Pulka, M.; De Laat, B.; De Groot, P. G.; Musial, J.
Objectives: Lupus anticoagulant (LA) is clinically the most relevant among all antiphospholipid antibody tests. Recently, new guidelines for LA detection were published. The objective of this retrospective cohort study was to compare tests recommended under these guidelines with other methods used f
Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian
The optimal and the most effective treatment of pulmonary embolism is still a matter of concern and each day sees a new set of challenges for the world of medicine. The progress, has been made in recent years, improved quality of life and caused much better treatment results. This is difficult issue in patients, receiving anticoagulant therapy, because they require an individual approach and adjustability to the therapeutic possibilities. The benefits of long-term anticoagulant therapy, which decreases relapses of idiopathic venous thromboembolism and diminishes risk of thromboembolic complications, should be taking under consideration. It is still a matter of dispute the time of carrying out of treatment, especially after the first life idiopathic episode of pulmonary embolism. The purpose of this paper is an overview and a summary of the foregoing achievements concerned the standards of idiopathic pulmonary embolism treatment, expecting benefits flowing with using new oral anticoagulants, as an alternative to known for decades Vitamin K antagonist drugs. A lot of information about new oral anticoagulants speaks in favor of their use, but unknown safety of the drugs caused searching the best strategy of pulmonary embolism treatment all the time. PMID:27591448
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 challenge
J.J. Hofstra; A.P. Vlaar; A.D. Cornet; B. Dixon; J.J. Roelofs; G. Choi; T. van der Poll; M. Levi; M.J. Schultz
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 challenge
Fábio Wildson Gurgel Costa
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.
Staerk, Laila; Fosbøl, Emil Loldrup; Gadsbøll, Kasper;
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%), rivar...
Kaliyamoorthy Kalidasan; Velayudham Ravi; Sunil Kumar Sahu; Murugan Lakshmi Maheshwaran; Kathiresan Kandasamy
Objective:To study the spine structure of stingray Himantura imbricata (H. imbricata) and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods:Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using methanol, ethanol, chloroform and acetone. Antibacterial activity was evaluated by disc diffusion technique against 10 human pathogens. Similarly, anticoagulant activity was also assessed by following United States Pharmacopeia method. Results:Light microscopic observation of spine revealed that the venom apparatus of the stingray H. imbricata consisted of two to three spines, glandular tissue and a sheath. The spine extract showed potent antibacterial activity against all tested pathogen. Maximum activity (14 mm) was found against Staphylococcus aureus. Crude extract showed 91.50 USP units/mg of anticoagulant activity. Conclusions: Microscopic observations gave new insight about the spine structure of the stingray. The spine extracts of H. imbricate showed potent activity against human pathogens revealed by the good zone of inhibition. Chloroform extracts conferred the most prominent antibacterial activity. The anticoagulant activity was also comparable with that of standard heparin.
Bobek, V.; Boubelík, Michael; Kovařík, J.; Taltynov, O.
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
Illán-Gala, Ignacio; Martínez-Sánchez, Patricia; Fuentes, Blanca; Llamas-Osorio, Yudy; Díaz de Terán, Javier; Báez, Melissa; Ruiz-Ares, Gerardo; Sanz-Cuesta, Borja Enrique; Lara-Lara, Manuel; Díez-Tejedor, Exuperio
Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010-2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR 2. 35 %of patients received IVT. Multivariate analyses showed that an INR ≥2 on admission was a factor associated with a higher probability of mild stroke (NIHSS mRS ≤2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT. PMID:26860861
Christensen, Henry; Lauterlein, Jens-Jacob; Sørensen, Patricia D;
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 to...
Levine, Mark N; Raskob, Gary; Beyth, Rebecca J; Kearon, Clive; Schulman, Sam
This chapter about hemorrhagic complications of anticoagulant treatment is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Bleeding is the major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varies considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism (VTE) is 70 years). Low molecular weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute VTE. UFH and LMWH are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. Information on bleeding associated with the newer generation of antithrombotic agents has begun to emerge. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk. PMID:15383476
Mice and rat populations are commonly controlled by two classes of rodenticide anticoagulants, coumarins and indandiones. However, poisoning of nontarget animals also often occurs. For cases such as these, a rapid, multi-residue method, which provides positive confirmation for both classes of antico...
Full Text Available Dental treatment performed in patients receiving oral anticoagulant drug therapy is becoming increasingly common in dental offices.The aim of oral anticoagulant therapy is to reduce blood coagulability to an optimal therapeutic range within which the patient is provided some degree of protection from thromboembolic events. This is achieved at the cost of a minor risk of haemorrhage. Frequently raised questions concern the safety and efficacy of the various anticoagulation regimens and their accompanying thromboembolic and bleeding risks relative to invasive dental procedures.The aim of this literature review is to evaluate the available evidence on the impact of anticoagulant medications on dental treatment and highlight certain patient management issues closely interrelated to various aspects of dental treatment. For that purpose literature search in the electronic database of Medscape, Pubmed-Medline, Science Direct, and EBSCO host, in the data base of Medical University Plovdiv and specialised published books in general medicine and dentistry was made.A total of 33 publications between 1995 and 2013 were identified: 12 review articles, 11 randomized controlled and non-randomised studies, 6 guidelines and practical guides, 1 meta-analysis and 3 specialised books.
Simmelink, MJA; Derksen, RHWM; Arnout, J; De Groot, PG
Lupus anticoagulants (LAC) are a heterogeneous group of autoantibodies that prolong phospholipid-dependent clotting assays. The autoantibodies that cause LAC activity are predominantly directed against beta(2)-glycoprotein I (beta(2)GPI) or prothrombin. In the present study, we describe a method to
Spronk, Henri M. H.; de Jong, Anne Margreet; Crijns, Harry J.; Schotten, Ulrich; Van Gelder, Isabelle C.; ten Cate, Hugo
Factor Xa and thrombin are well-known components of the coagulation cascade and have been proven to be viable targets for effective anticoagulation treatment. However, accumulating evidence suggests that these serine proteases are also crucial modulators of other cellular mechanisms through the acti
Objective To evaluate the safety and efficacy of regional citrate anticoagulation in sustained low efficiency dialysis (SLED) .Methods A total of 45 patients with acute kidney injury (AKI) or end stage renal disease (ESRD) admitted in our hospital from August 2011 to
Zhang, Xiao; Zhao, Xiaoliang; Lang, Yinzhi; Li, Qinying; Liu, Xiaoxiao; Cai, Chao; Hao, Jiejie; Li, Guoyun; Yu, Guangli
Heparin (HP) is a promising agent for anti-Alzheimer's disease (AD), but its anticoagulant activity limits its applications. So a low anticoagulant heparin (LAH) with anti-AD effect is needed. A novel LAH and heparan sulfate (HS) were purified from crude porcine intestinal heparin. Their structures were characterized by nuclear magnetic resonance and liquid chromatography-mass spectrometry. LAH had a relatively high degree of sulfation, but lower than that of HP. 3-O-Sulfated-containing glucosamine residues further confirmed the low anticoagulant activity of LAH. Sixteen oligosaccharides of LAH and HS were prepared and assigned. Evaluation of anti-BACE-1 activities suggested that their potencies were positively correlated with degree of sulfation and polymerization of oligosaccharides. Besides, LAH-derived hexa- to dodecasaccharides was promised to be administrated in vitro as BACE-1 inhibitors. This study presented ideal BACE-1 inhibitors, LAH-derived oligosaccharides, with virtually no anticoagulant activities, which were promised to be excellent leads for treatment of AD. PMID:27474542
Full Text Available Objective: To study the spine structure of stingray Himantura imbricata (H. imbricata and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods: Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using methanol, ethanol, chloroform and acetone. Antibacterial activity was evaluated by disc diffusion technique against 10 human pathogens. Similarly, anticoagulant activity was also assessed by following United States Pharmacopeia method. Results: Light microscopic observation of spine revealed that the venom apparatus of the stingray H. imbricata consisted of two to three spines, glandular tissue and a sheath. The spine extract showed potent antibacterial activity against all tested pathogen. Maximum activity (14 mm was found against Staphylococcus aureus. Crude extract showed 91.50 USP units/mg of anticoagulant activity. Conclusions: Microscopic observations gave new insight about the spine structure of the stingray. The spine extracts of H. imbricate showed potent activity against human pathogens revealed by the good zone of inhibition. Chloroform extracts conferred the most prominent antibacterial activity. The anticoagulant activity was also comparable with that of standard heparin.
Gómez-Canela, Cristian; Lacorte, Silvia
The occurrence of 10 commonly used anticoagulant rodenticides in centrifuged sludge of 27 wastewater treatment plants was evaluated using solid-liquid extraction (SLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Activated carbon, alumina, and Florisil cartridges with methanol/dichloromethane as eluting solvents were tested in combination with primary-secondary amine (PSA) to optimize an efficient sample cleanup. PSA in combination with Florisil was the best methodology to extract anticoagulant rodenticides in sludge providing recoveries between 42 ± 0.5 and 100 ± 2 %. Warfarin, bromadiolone, ferulenol, and coumachlor were the most ubiquitous compounds in sludge at concentrations up to 84.2 ng g(-1) for the latter. Coumatetralyl, dicoumarol, and brodifacoum were detected sporadically at levels between 6.1 and 17.4 ng g(-1). On the contrary, acenocoumarol, difenacoum, and flocoumafen were not detected in any sample. Finally, we estimated the amount of anticoagulant rodenticides discharged via sludge in order to determine the potential impact to agricultural soil according to different sludge usage practices in the region investigated. This study demonstrates that anticoagulant rodenticides are accumulated in sludge during activated sludge treatment and that the application of sludge as fertilizers may pose a future environmental risk, if not controlled. PMID:27146526
Dowding, Claire V., E-mail: email@example.com [School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG (United Kingdom); Shore, Richard F.; Worgan, Andrew [NERC Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Baker, Philip J.; Harris, Stephen [School of Biological Sciences, University of Bristol, Woodland Road, Bristol BS8 1UG (United Kingdom)
Studies on exposure of non-targets to anticoagulant rodenticides have largely focussed on predatory birds and mammals; insectivores have rarely been studied. We investigated the exposure of 120 European hedgehogs (Erinaceus europaeus) from throughout Britain to first- and second-generation anticoagulant rodenticides (FGARs and SGARs) using high performance liquid chromatography coupled with fluorescence detection (HPLC) and liquid-chromatography mass spectrometry (LCMS). The proportion of hedgehogs with liver SGAR concentrations detected by HPLC was 3-13% per compound, 23% overall. LCMS identified much higher prevalence for difenacoum and bromadiolone, mainly because of greater ability to detect low-level contamination. The overall proportion of hedgehogs with LCMS-detected residues was 57.5% (SGARs alone) and 66.7% (FGARs and SGARs combined); 27 (22.5%) hedgehogs contained >1 rodenticide. Exposure of insectivores and predators to anticoagulant rodenticides appears to be similar. The greater sensitivity of LCMS suggests that hitherto exposure of non-targets is likely to have been under-estimated using HPLC techniques. - Exposure of insectivorous hedgehogs to anticoagulant rodenticides in Britain is similar to predatory birds and mammals that specialise in eating small mammals, and hitherto exposure levels have been under-estimated using HPLC techniques.
Keung, Y K; Cobos, E; Meyerrose, G E; Roberson, G H
We report a case of diffuse large cell non-Hodgkin's lymphoma with concomitant lupus anticoagulant at initial diagnosis. Progressive thrombosis occurred despite radiologically proven response of the lymphoma after chemotherapy treatment. Extraordinary bone scintigraphy with multiple "cold" lesions probably due to bone ischemia is described. PMID:8624478
Jones, Cindy; Lacombe, Guy
Integrating specialized pharmacist services and follow-up with the laboratory, home care nursing, retail pharmacy and physicians can ensure optimal outcomes for patients receiving anticoagulation, or "blood thinner," therapy. Improved patient education and discharge care planning can bridge disconnects, enable patients to better manage their care and ensure better patient outcomes and more effective use of health system resources. Specially trained pharmacists can provide safe and effective management of a high-alert medication to help prevent potentially life-threatening clots or bleeding. With advanced prescribing authorization, the pharmacist can seamlessly provide this service both locally in a community and via Telehealth to surrounding areas, potentially for any Albertan. Warfarin therapy may be lifelong or short-term (three to six months), but all patients require regular monitoring with blood tests. Many variables, both lifestyle and medication related, can impact therapy, and through extensive education and access via telephone to an "expert" for questions and follow-up of blood tests, patients are empowered to better regulate their anticoagulants. Anticoagulation pharmacists, as part of an AMS (anticoagulation management service), can provide a continuum of care for patients while in hospital, when discharged home, as an outpatient in the community or as a resident of a long-term care facility or seniors' home. PMID:20057253
Ernestus, R I; Speder, B; Pakos, P; Hildebrandt, G; Klug, N
Intracerebral hemorrhage (ICH) during oral anticoagulation is a serious complication, which is mostly fatal for the multimorbid patient. In the present retrospective study of 53 patients with ICH during treatment with a cumarin derivative (Phenoprocoumon, Marcumar), we investigated the relationship between therapy and preexisting parameters such as age, location, level of consciousness, additional bleeding risks, and the degree of anticoagulation, which were assumed to be of prognostic relevance. The therapeutic management of ICH during treatment with anticoagulants was determined predominantly by location of the hematoma, patient's age, and additional bleeding risks, but less by level of consciousness and initial thromboplastin time (Quick's test). As a consequence of the individual analysis of these 5 parameters, age over 60 years, location of hematoma in the midline or ventricles, coma, additional bleeding risks such as arterial hypertension and trauma, and Quick's test below 15% at the time of bleeding were supposed to be responsible for poor prognosis. Mortality increased with a rising number of poor prognostic factors, independently of surgical or conservative treatment. In consequence, prognosis of ICH during oral anticoagulation is predominantly influenced by the number of such disadvantageous indicators and only little by therapy. PMID:8053274
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.
Laith G. Alsayegh
Full Text Available Novel oral anticoagulants (NOACs are becoming popular management options for stroke prophylaxis in nonvalvular atrial fibrillation as well as deep vein thrombosis and pulmonary embolism treatment and prophylaxis. NOACs have similar efficacy to warfarin along with noninferior safety profiles. Patient comorbidities, size, renal and hepatic function, and concomitant drug regimen play a role in which NOAC a physician may choose.
Laith G. Alsayegh
Novel oral anticoagulants (NOACs) are becoming popular management options for stroke prophylaxis in nonvalvular atrial fibrillation as well as deep vein thrombosis and pulmonary embolism treatment and prophylaxis. NOACs have similar efficacy to warfarin along with noninferior safety profiles. Patient comorbidities, size, renal and hepatic function, and concomitant drug regimen play a role in which NOAC a physician may choose.
Chan, Noel C; Eikelboom, John W; Weitz, Jeffrey I
The direct oral anticoagulants (DOACs) represent a major advance in oral anticoagulant therapy and have replaced the vitamin K antagonists as the preferred treatment for many indications. By simplifying long-term anticoagulant therapy and improving its safety, the DOACs have the potential to reduce the global burden of thrombosis. Postmarketing studies suggest that the favorable results achieved with DOACs in the randomized controlled trials can be readily translated into practice, but highlight the need for appropriate patient, drug and dose selection, and careful follow-up. Leveraging on their success to date, ongoing studies are assessing the utility of DOACs for the prevention of thrombosis in patients with embolic stroke of unknown source, heart failure, coronary artery disease, peripheral artery disease, antiphospholipid syndrome, and cancer. The purpose of this article is to (1) review the pharmacology of the DOACs, (2) describe the advantages of the DOACs over vitamin K antagonists, (3) summarize the experience with the DOACs in established indications, (4) highlight current challenges and limitations, (5) highlight potential new indications; and (6) identify future directions for anticoagulant therapy. PMID:27126650
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
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.
Full Text Available Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS. We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20-0.71. Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69-0.86 and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78-0.97 were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08-1.33. In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes.
Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla
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. PMID:24919144
King, Adam B; O'Duffy, Anne E; Kumar, Avinash B
We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus. She was started on systemic anticoagulation and underwent mechanical clot removal and catheter-directed endovascular thrombolysis with limited success. Complicating the intensive care unit care was the development of heparin resistance, with an inability to reach the target partial thomboplastin time (PTT) of 60 to 80 seconds. At her peak heparin dose, she was receiving >35 000 units/24 h, and her PTT was subtherapeutic at <50 seconds. Deficiency of ATIII was suspected as a possible etiology of her heparin resistance. Fresh frozen plasma was administered for ATIII level repletion. Given her high thrombogenic risk and challenges with conventional anticoagulation regimens, we transitioned to argatroban for systemic anticoagulation. Heparin produces its major anticoagulant effect by inactivating thrombin and factor X through an AT-dependent mechanism. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and the AT. A deficiency of AT leads to a hypercoagulable state and decreased efficacy of heparin that places patients at high risk of thromboembolism. Heparin resistance, especially in the setting of critical illness, should raise the index of suspicion for AT deficiency. Argatroban is an alternate agent for systemic anticoagulation in the setting of heparin resistance. PMID:27366296
Wiggins, Barbara S; Northup, Amanda; Johnson, Dominic; Senfield, Jeffrey
Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant
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. PMID:27217793
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)
Full Text Available Area of drug delivery is vast, and various advances have been made in the medical field. Besides the versatility in the dosage forms, various orders for the drug release are known, which includes zero order, first order, Higuchi model, Hixon Crowell model and Korsmeyer Peppas model. In vitro dissolution is recognized as an important element in the development of drug. The nature of the drug such as its shape, crystallinity, particle size and solubility reflects the kinetics of the drug. Various models are used to study the dissolution profiles of the new drug substances. Qualitative and quantitative changes in the drug alters the drug release and performance that is action of drug in the body, which is in vivo performance. Various model dependent methods and model independent methods have been taken into consideration for studying the drug release kinetics.
Al-Gousous, Jozef; Langguth, Peter
Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. PMID:25546430
Full Text Available The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses. Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at –20, 7 and 25°C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below 7°C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.
Assadi, Farahnak; Shahrbaf, Fatemeh Ghane
The dosage of drugs in patients requiring continuous renal replacement therapy need to be adjusted based on a number of variables that that affect pharmacokinetics (PK) including patient weight, CRRT modality (convention, vs. diffusion), blood and/or effluent flow, hemofilter characteristics, physiochemical drug properties, volume of distribution, protein binding and half-life as well as residual renal function. There is a paucity of data on PK studies in children with acute kidney injury requiring CRRT. When possible, therapeutic drug monitoring should be utilized for those medications where serum drug concentrations can be obtained in a clinically relevant time frame. Also, a patient-centered team approach that includes an intensive care unit pharmacist is recommended to prevent medication-related errors and enhance safe and effective medication use is highly recommended. The aim of this article is to review the current guidelines for drug dosing in critically ill children who require continuous venovenous hemofiltration. PMID:26709896
Full Text Available Two, simple, accurate, rapid and sensitive methods have been developed for the estimation of famciclovir in tablet dosage forms. Method A is based on the nucleophillic substitution product with Folin′s reagent to form colored chromogen exhibiting absorption maximum at 454 nm with apparent molar absorptivity of 3.99x10 4 l/mol.cm and obeyed Beer′s law in the concentration range of 2-10 µg/ml. Method B is based on diazotisation and coupling reaction with resorcinol to form colored chromogen exhibiting absorbance maximum at 386 nm with apparent molar absorptivity of 3.15x10 4 l/mol.cm and obeyed Beer′s law in the concentration range of 7-21 µg/ml.
Full Text Available A simple and sensitive spectrophotometric method has been developed for the estimation of lomefloxacin hydrochloride in its marketed formulations. The method is based on the reaction between the drug and the dichlone, in the presence of crotonaldehyde in dimethylsulfoxide, which produces a blue chromogen with absorption maximum at 645 nm. The good agreement with Beer′s law was found in the concentration range of 5-100 µg/ml. The optimum reaction conditions and other analytical parameters are evaluated. Statistical comparison of the results with those of reported method shows good agreement, and indicated no significant difference in precision. The proposed method was found to be simple, accurate, and reproducible for the routine analysis of the drug in pharmaceutical dosage forms.
Full Text Available Laura A Michielsen,1 Frank MMA van der Heijden,1 Paddy KC Janssen,2 Harold JH Kuijpers11Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; 2Department of Pharmacy, VieCuri Medical Centre, Venlo, the NetherlandsBackground: The aim of this retrospective study was to explore the relationship between psychotropic medication dosage and birth outcomes.Methods: A total of 136 women were enrolled, who had an active mental disorder, were taking medication to prevent a relapse, or had a history of postpartum depression or psychosis. Medication use was evaluated for the three trimesters and during labor. Based on the defined daily dose, medication use was classified into three groups. Primary outcome variables included the infant gestational age at birth, birth weight, and Apgar scores at one and 5 minutes.Results: Our study showed a significantly higher incidence of Apgar score ≤7 at 5 minutes in women taking psychotropic drugs as compared with the group taking no medication, respectively (16.3% versus 0.0%, P=0.01. There was no significant difference between the two groups in Apgar score at one minute or in gestational age and birth weight. The results showed no significant differences in gestational age, birth weight, or Apgar scores for a low–intermediate or high dose of a selective serotonin reuptake inhibitor and for a low or intermediate dose of an antipsychotic.Conclusion: This study does not indicate a relationship between doses of selective serotonin reuptake inhibitors and antipsychotics and adverse neonatal outcomes.Keywords: pregnancy, psychotropic medication, dosage, birth outcomes
Assessing dissolution and Caco-2 permeability to estimate the in vivo performance of solid oral dosage forms is done since decades. However, permeability assays applying Caco-2 monolayers exhibit the drawback that, in contrast to dissolution testing, a complete dosage form is not eligible for conventional epithelial permeability assays. Hence, an apparatus was developed providing the possibility to assess permeability of solid oral dosage forms based on combination of a Caco-2 monolayer and a...
Valizadeh, Sousan; Rasekhi, Mehri; Hamishehkar, Hamed; Asadollahi, Malihe; Hamishehkar, Hadi
Objective: Considering the inability of neonates to swallow oral drugs in the form of solid tablets, the lack of appropriate dosage forms for infants, and the necessity to prepare some pills for neonates, the current study investigated dosage accuracy in drugs for neonates prepared from tablets by analyzing the concentrations of final products. Methods: Captopril and spironolactone, oral dosage forms that are not suitable for infants, were chosen as the drug model for this study. Demographic ...
Zimmer, Fabian; Harrison, Peter W; Dessimoz, Christophe; Mank, Judith E
In many diploid species, sex determination is linked to a pair of sex chromosomes that evolved from a pair of autosomes. In these organisms, the degeneration of the sex-limited Y or W chromosome causes a reduction in gene dose in the heterogametic sex for X- or Z-linked genes. Variations in gene dose are detrimental for large chromosomal regions when they span dosage-sensitive genes, and many organisms were thought to evolve complete mechanisms of dosage compensation to mitigate this. However, the recent realization that a wide variety of organisms lack complete mechanisms of sex chromosome dosage compensation has presented a perplexing question: How do organisms with incomplete dosage compensation avoid deleterious effects of gene dose differences between the sexes? Here we use expression data from the chicken (Gallus gallus) to show that ohnologs, duplicated genes known to be dosage-sensitive, are preferentially dosage-compensated on the chicken Z chromosome. Our results indicate that even in the absence of a complete and chromosome wide dosage compensation mechanism, dosage-sensitive genes are effectively dosage compensated on the Z chromosome. PMID:27044516
Full Text Available Antonio Gómez-Outes,1 M Luisa Suárez-Gea,1 Ramón Lecumberri,2 Ana Isabel Terleira-Fernández,3,4 Emilio Vargas-Castrillón,3,4 Eduardo Rocha51Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices, Madrid, 2Department of Hematology, University Clinic of Navarra, Pamplona, 3Department of Clinical Pharmacology, Hospital Clínico, Madrid, 4Department of Pharmacology, Universidad Complutense, Madrid, 5Department of Hematology, School of Medicine, University of Navarra, Pamplona, SpainAbstract: Venous thromboembolism (VTE, encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs, supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents, and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number. New anticoagulants in development for prophylaxis
Jacobs, Victoria; May, Heidi T; Bair, Tami L; Crandall, Brian G; Cutler, Michael J; Day, John D; Mallender, Charles; Osborn, Jeffrey S; Stevens, Scott M; Weiss, J Peter; Woller, Scott C; Bunch, T Jared
Direct oral anticoagulants (DOACs) have been used in clinical practice in the United States for the last 4 to 6 years. Although DOACs may be an attractive alternative to warfarin in many patients, long-term outcomes of use of these medications are unknown. We performed a propensity-matched analysis to report patient important outcomes of death, stroke/transient ischemic attack (TIA), bleeding, major bleeding, and dementia in patients taking a DOAC or warfarin. Patients receiving long-term anticoagulation from June 2010 to December 2014 for thromboembolism prevention with either warfarin or a DOAC were matched 1:1 by index date and propensity score. Multivariable Cox hazard regression was performed to determine the risk of death, stroke/TIA, major bleed, and dementia by the anticoagulant therapy received. A total of 5,254 patients were studied (2,627 per group). Average age was 72.4 ± 10.9 years, and 59.0% were men. Most patients were receiving long-term anticoagulation for AF management (warfarin: 96.5% vs DOAC: 92.7%, p <0.0001). Rivaroxaban (55.3%) was the most commonly used DOAC, followed by apixaban (22.5%) and dabigatran (22.2%). The use of DOACs compared with warfarin was associated with a reduced risk of long-term adverse outcomes: death (p = 0.09), stroke/TIA (p <0.0001), major bleed (p <0.0001), and bleed (p = 0.14). No significant outcome variance was noted in DOAC-type comparison. In the AF multivariable model patients taking DOAC were 43% less likely to develop stroke/TIA/dementia (hazard ratio 0.57 [CI 0.17, 1.97], p = 0.38) than those taking warfarin. Our community-based results suggest better long-term efficacy and safety of DOACs compared with warfarin. DOAC use was associated with a lower risk of cerebral ischemic events and new-onset dementia. PMID:27236255
McNair, E; Marcoux, J-A; Bally, C; Gamble, J; Thomson, D
Heparin resistance (unresponsiveness to heparin) is characterized by the inability to reach acceptable activated clotting time values following a calculated dose of heparin. Up to 20% of the patients undergoing cardiothoracic surgery with cardiopulmonary bypass using unfractionated heparin (UFH) for anticoagulation experience heparin resistance. Although UFH has been the "gold standard" for anticoagulation, it is not without its limitations. It is contraindicated in patients with confirmed heparin-induced thrombocytopenia (HIT) and heparin or protamine allergy. The safety and efficacy of the use of the direct thrombin inhibitor bivalirudin for anticoagulation during cardiac surgery has been reported. However, there have been no reports on the treatment of heparin resistance with bivalirudin during CPB. In this review, we report the favorable outcome of our single-center experience with the alternative use of bivalirudin in the management of anticoagulation of heparin unresponsive patients undergoing coronary artery bypass graft surgery. PMID:25934498
Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A
BACKGROUND: 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 wheth
Boyd, Jason L.; Du, Brian; Vaksman, Zalman; Locke, James P.; Putcha, Lakshmi
The NASA Reduced Gravity Office (RGO) uses scopolamine (SCOP) and in combination with dextoamphetamine (DEX) to manage motion sickness symptoms during parabolic flights. The medications are dispensed as custom dosage forms as gelatin capsules. Anecdotal evidence of efficacy suggests that these formulations are unreliable and less efficacious for the treatment of motion sickness. We estimated bioavailability of four different oral formulations used by NASA for the treatment of motion sickness. Twelve healthy, non-smoking subjects between 21and 48 years of age received four treatments on separate days in a randomized fashion; the treatments were 0.8 mg SCOP alone as tablet, 0.8 mg SCOP alone in gel cap, 0.8 mg SCOP and 10 mg DEX as tablets, and 0.8 mg SCOP and 10 mg DEX in gel cap. After each treatment, blood, saliva, and urine samples were collected at scheduled time intervals for 24 h after dosing. Bioavailability and pharmacokinetic parameters were calculated and compared using ANOVA. After administration of SCOP tablets alone, maximum concentration (C(sub max)) and time for maximum concentration (t(sub max)) were 0.26 plus or minus 0.04 ng/mL and 0.71 plus or minus 0.02 h, respectively; volume of distribution, and clearance were 47.6 plus or minus 4.72 L/kg and 23.0 plus or minus 4.58 L/h/kg, respectively. SCOP t(sub max) after administration as gelcaps was significantly longer than that with tablets (1.04 h, p less than 0.05), but no significant differences in other pharmacokinetic parameters of SCOP were observed between the two dosage forms. When coadministered with DEX, the area underneath the concentration versus time curve (AUC) of SCOP was significantly reduced to 0.61 plus or minus 0.09 and 0.64 plus or minus 0.11 ng (raised dot) h/mL after administration as a tablet or gelcap formulation, respectively; SCOP C(sub max) was lower after coadministration with DEX, this difference, however, was not statistically significant. Delayed absorption with gelcaps
Full Text Available Three series of trials involving 10 domestic short-haired cats were carried out to determine the influence of dosage of contrast media or type of chemical restraint on feline excretory urography. The 1st series (group A involved 5 cats sedated with 2.0 mg/kg intramuscular (i.m injection of 2 % xylazine and receiving 800 mg/kg of 76 % meglumine diatrizoate (urografin. The 2nd series (group B involved another 5 cats sedated with 2.0 mg/kg (i.m injection of 2 % xylazine and receiving 1200 mg/kg of 76% urografin. The 3rd series (group C involved the repeat urography of the group B cats but sedated with 15 mg/kg (i.m injection of 5% ketamine hydrochloride. Ventrodorsal radiographs were obtained immediately, 5, 15 and 40 minutes after the injection of 76 % urografin. Scores were assigned to nephrographic opacification as described in the literature. The heart rates, respiratory rates and rectal temperatures of the cats were also determined before sedation, after sedation, immediately after the injection of 76 % urografin and at 15-minute intervals over a period of 60 minutes. In this study, there were significant differences (P < 0.05 in the nephrographic opacification scores between the group A and group B cats at times 0 and 40 minutes post-administration of urografin. Group A cats had good initial nephrographic opacification which faded later while the nephrographic opacification of group B cats progressively increased. Similarly, nephrographic opacification was significantly (P < 0.05 higher in the xylazine-sedated cats (groups A and B than the ketamine-sedated cats (group C. However, there were no significant differences (P > 0.05 in heart rates, respiratory rates and rectal temperatures between the 3 groups of cats. It was therefore concluded that increasing the dosage of urografin above 800 mg/kg in cats does not provide additional beneficial effects on the nephrograms produced. Xylazine sedation was observed to produce better nephrographic
Fumagalli, Stefano; Cardini, Francesca; Roberts, Anna T.; Boni, Serena; Gabbai, Debbie; Calvani, Silvia; Casalone Rinaldi, Marta; Manetti, Stefania; Tarantini, Francesca; Marchionni, Niccolò
Background and aims: Atrial fibrillation (AF) is the most common arrhythmia in elderly people, yet oral anticoagulation is underused in the aged. We tried to determine whether new oral anticoagulants (NOA) have greater psychological tolerability than warfarin. Methods: Age-, gender-matched groups of AF patients receiving NOA (N = 15) or warfarin (N = 15) were assessed with the Anti-Clot Treatment Scale (ACTS) and the Perceived Stress Scale (PSS). Results: Patients were old (81 ...
Wong, Christopher X; Odutayo, Ayodele; Emdin, Connor A; Kinnear, Ned J; Sun, Michelle T
Atrial fibrillation (AF) is common in patients on dialysis. Although randomized trials of anticoagulation for AF have demonstrated striking reductions in stroke, these trials did not recruit patients on dialysis. We thus undertook this systematic review and meta-analysis of observational studies including patients with AF on dialysis that reported associations of anticoagulation use. Twenty studies involving 529,741 subjects and 31,321 patients with AF on dialysis were identified. Anticoagulation was associated with a 45% (95% CI 13% to 88%) increased risk of any stroke, reflecting a nonsignificant 13% (95% CI -4% to 34%) increased ischemic stroke risk and 38% (95% CI 3% to 85%) increased hemorrhagic stroke risk. There was also a 44% (95% CI 38% to 56%) lower risk of any thromboembolism, and a 31% (95% CI 12% to 53%) increased risk of any bleeding but no clear association with cardiovascular death (relative risk 0.99, 95% CI 0.86 to 1.15) or all-cause mortality (relative risk 0.97, 95% CI 0.90 to 1.04). Incident event rates were similar or worse in patients on anticoagulation. In conclusion, these observational analyses provide little supporting evidence of benefit, and instead suggest harm, from anticoagulation in patients on dialysis with AF. These results raise the possibility that the effects of anticoagulation in patients with AF on dialysis may not be similar to the clear benefit of anticoagulation seen in patients with AF without end-stage renal disease. Randomized trials are required to definitively evaluate the safety and efficacy of anticoagulation for AF in the dialysis setting. PMID:27237624
Dinorah Herenia Mulet Batista; Carlos Ramírez Pérez; Gladis Abreu Sera; Juan Pérez Mir; Jesús Alberto Pérez González
The international normalized ratio (INR) is the primary tool for assessing patients undergoing oral anticoagulant therapy. It was created from the need of standardizing the different types of thromboplastins, regardless of their origin, from which the figures of the true anticoagulation state desired by the physician depend, mainly in patients at risk of thromboembolic events. The objective of this work is to show the simple technique of determining this ratio so that it can be extended to an...
Sucker, Christoph; Mansmann, Georg; Steiner, Stefan; Gattermann, Norbert; Schmitt-Graeff, Anette; Loncar, Robert; Scharf, Rudiger E; Stockschlader, Marcus
A 37-year-old female patient with systemic mastocytosis who was admitted with severe unexplained bleeding symptoms is studied. Laboratory procedures established the diagnosis of a patient-derived-heparin-like anticoagulant as a very rare hemostatic abnormality predisposing to bleeding. The patient died from refractory disease despite therapy with protamine, initiation of chemotherapy, and supportive measures. The case illustrates the clinical presentation and diagnosis of heparin-like anticoagulants. Etiology, pathophysiology, and therapeutic options are discussed. PMID:18160568
Alegret, Josep M; Viñolas, Xavier; Arias, Miguel A.; Martínez-Rubio, Antoni; Rebollo, Pablo; Ràfols, Carles; Martínez-Sande, José L.
New oral anticoagulants (NOAC) have demonstrated their efficacy as an alternative to vitamin K antagonists (VKA) in the prophylaxis of cardioembolic events in patients with atrial fibrillation (AF). However, evidence on the benefits of NOAC in health-related quality of life (HRQoL) is lacking.We evaluated changes in HRQoL related to oral anticoagulation therapy employing a specific questionnaire in a cohort of 416 patients with AF undergoing electrical cardioversion. In terms of HRQoL, we obs...
The programmer's task is often taken to be the construction of algorithms, expressed in hierarchical structures of procedures: this view underlies the majority of traditional programming languages, such as Fortran. A different view is appropriate to a wide class of problem, perhaps including some problems in High Energy Physics. The programmer's task is regarded as having three main stages: first, an explicit model is constructed of the reality with which the program is concerned; second, this model is elaborated to produce the required program outputs; third, the resulting program is transformed to run efficiently in the execution environment. The first two stages deal in network structures of sequential processes; only the third is concerned with procedure hierarchies. (orig.)
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... part 522 is amended as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... Medicine, 21 CFR part 522 is amended as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New...--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for 21 CFR part...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... part 522 is amended as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... part 522 is amended as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation and Injectable Dosage Form New...: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New...--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for 21 CFR part...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 522 Implantation or Injectable Dosage Form New... as follows: PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS 0 1. The...
... 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...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New...--OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS 0 1. The authority citation for 21 CFR part 524...
... parasites that were approved for the pioneer product with 3 years of marketing exclusivity (69 FR 501... HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New... part 524 is amended as follows: PART 524--OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS 0 1....
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New... Veterinary Medicine, 21 CFR part 524 is amended as follows: PART 524--OPHTHALMIC AND TOPICAL DOSAGE FORM...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 Ophthalmic and Topical Dosage Form New... Veterinary Medicine, 21 CFR part 524 is amended as follows: PART 524--OPHTHALMIC AND TOPICAL DOSAGE FORM...
Manley, H J; Smith, J A; Garris, R E
Low-molecular-weight heparins have been administered for a variety of clinical conditions. A patient with a mechanical aortic valve replacement patient underwent elective transurethral prostatectomy. Anticoagulation was managed with unfractionated heparin immediately preoperatively and postoperatively. Warfarin was begun on postoperative day 1. The patient had a prolonged hospitalization due to subtherapeutic international normalized ratios (INR) despite warfarin administration. Because he intended to leave the hospital against medical advice before therapeutic INR was achieved, enoxaparin 1 mg/kg subcutaneously every 12 hours was prescribed to provide anticoagulation, facilitating discharge and improving the patient's quality of life. Enoxaparin was associated with an approximate saving of $4500 over warfarin. The only adverse event reported was bruising at the injection site. PMID:9545164
Drozd, N N; Tolstenkov, A S; Bannikova, G E; Miftakhova, N T; Lapikova, E S; Makarov, V A; Varlamov, V P
The anticoagulant activity of low-molecular weight heparins (LMWH-PC) with average distribution of molecular weights within 3.4-5.8 kD was investigated. The samples of LMWH-PC were obtained from unfractionated heparin using immobilized enzyme complex of protease C. The LMWH-PC derivatives inhibited the activity of blood coagulation factors IIa (thrombin) and Xa. The LMWH-PC derivatives had an anti-factor-Xa activity up to 131-208 IU/mg and anti-factor-IIa activity up to 81-175 IU/mg. All LMWH-PC derivatives form complexes with protamine sulfate during electrophoresis in agarose gel. The anticoagulant activity of rabbit plasma exhibits a doze-dependent increase upon the intravenous or subcutaneous injection of LMWH-PC with a molecular weight of 5.4 kD. PMID:18318190
A. A. Rumyantsev
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.
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.
Guo, Weihua; Zhu, Jian; Cheng, Zhenping; Zhang, Zhengbiao; Zhu, Xiulin
Polished 316 L stainless steel (SS) was first treated with air plasma to enhance surface hydrophilicity and was subsequently allowed to react with 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane to introduce an atom transfer radical polymerization (ATRP) initiator. Accordingly, the surface-initiated atom transfer radical polymerization of polyethylene glycol methacrylate (PEGMA) was carried out on the surface of the modified SS. The grafting progress was monitored by water contact angle measurements, X-ray photoelectron spectroscopy and atomic force microscopy. The polymer thickness as a function different polymerization times was characterized using a step profiler. The anticoagulative properties of the PEGMA modified SS surface were investigated. The results showed enhanced anticoagulative to acid-citrate-dextrose (ACD) blood after grafting PEGMA on the SS surface. PMID:21528878
Adepoju, GKA; Adeyemi, T
Aim: Citrus aurantifolia (Family Rutaceae) is commonly known as a familiar food and medicine, and s therapeutic effectiveness in a variety of diseases has been suggested in traditional medicine. Various complementary and alternative medicines (CAM) have been shown to interact with orthodox medicines. Hence, the aim of this study is to investigate such a phenomenon particularly the interaction of lime fruit juice with warfarin. Materials and Method: Wistar strain albino rats of both sexes weighing between 190 and 230g were administered with oral doses of the respective drugs used depending on the groups of animals. Effects on the anticoagulant activity of warfarin were determined by standard laboratory methods. Result: Lime fruit juice caused a reduction in the anticoagulant activity of warfarin. Conclusion: This finding has shown that CAM can interact with orthodox medicines hence, warfarin prescribers need to be aware of the usage of CAM and monitor the international normalized ratio (INR) of their patients more frequently. PMID:21042484
Andrew D Blann
Full Text Available Andrew D Blann, Chee W KhooUniversity Department of Medicine, City Hospital, Birmingham, UKAbstract: As the risk factors for thrombosis are becoming better understood, so is the need for anticoagulation. The inherent difficulties with warfarin are such that a low-molecular-weight heparin (LMWH is often the key therapeutic. However, there are several different species of LMWH available to the practitioner, which leads to the need for an objective guide. New agents are coming onto the marketplace, and these may supersede both warfarin and the heparins. The current report will review the biochemistry and pharmacology of different LWMHs and identify which are more suitable for the different presentations of venous thromboembolism. It will conclude with a brief synopsis of new agents which may supersede warfarin and heparin.Keywords: thrombosis, warfarin, heparin, anticoagulation
The determination of 90Sr in bones by dosage of its daughter product 90Y is a 4-step process: 1) elimination of the phosphate ions by precipitation of the Ca and Sr as oxalate in the presence of acid; 2) reduction in the calcium concentration to a suitable level by the addition of a known volume of nitric acid (a single precipitation is sufficient), the precipitation yield of the strontium nitrate is checked by the measurement of the amount of 85Sr added as tracer; 3) purification by a yttrium hydroxide precipitation; 4) extraction at equilibrium of the 90Y which is counted to give the concentration. By using 50 gm of ash it is possible to detect about 0.1 pCi of 90Sr per gram of calcium. The advantages of this technique: -) treatment of a large quantity of bone ash -) the use of a small volume of nitric acid (less than 2 ml/g of ash, and -) the various operations present no difficulty. (authors)
Łaszcz, Marta; Witkowska, Anna
Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10 mg and 30 mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify(®) 10 mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III. PMID:26397209
Al-Ghanam, S M; Belal, F
A simple and sensitive spectrophotometric method has been developed for the determination of diloxanide furoate in its dosage forms. The method is based on the reaction of the drug with potassium permanganate in the presence of sodium hydroxide to produce a bluish green coloured species measurable at 610 nm. The absorbance-concentration plot is linear over the range 2.5-20 microg/ml with correlation coefficient (n = 8) of 0.9998 and minimum detectability of 0.2 microg/ml (6.1 x 10(-7) M). The molar absorptivity was 1.1 x 10(4) l/mol cm. The different experimental parameters affecting the development and stability of the colour were carefully studied and optimised. The proposed method was applied successfully for the determination of diloxanide furoate in its tablet form. The results obtained were in good agreement with those obtained using the official method. The proposed method could be applied to the determination of diloxanide furoate in presence of some co-formulated drugs. The effect of sensitisers and surfactants on the performance of the proposed method was also studied. A proposal of the reaction pathway was presented. PMID:11680811
Hossein Zolfagharian; Mohammad Mohajeri; Mahdi Babaie
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 ...
Tarik; Khouya; Mhamed; Ramchoun; Abdelbassat; Hmidani; Souliman; Amrani; Hicham; Harnafi; Mohamed; Benlyas; Younes; Filali; Zegzouti; Chakib; Alem
Objective: To evaluate the anti-inflammatory, anticoagulant and antioxidant effects of aqueous extracts of thyme varieties from Moroccan.Methods: The aqueous extracts of tree medicinal plants [Thymus atlanticus(T. atlanticus), Thymus satureioides and Thymus zygis(T. zygis)] were screened for their antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl radical-scavenging, ferric reducing antioxidant power assay, radical scavenging activity method, the inhibition of 2,2’-azobis(2-amidinopropane) dihydrochloride that induces oxidative erythrocyte hemolysis and thiobarbituric acid reactive substances assay. The anti-inflammatory activity of aqueous extracts was evaluated in vivo using croton oil-induced ear edema and carrageenan-induced paw edema in mice and rats, respectively. This extracts were evaluated in vitro for their anticoagulant activity at the different concentrations by partial thromboplastin time and prothrombin time activated. Results: All thyme varieties were found to possess considerable antioxidant activity and potent anti-inflammatory activity in the croton oil-induced edema. Administration of aqueous extracts of two varieties(50 mg/kg)(T. zygis and T. atlanticus) reduced significantly the carrageenaninduced paw edema similar to non-steroidal anti-inflammatory drug(indomethacin, 10 mg/kg). In partial thromboplastin time and prothrombin time tests, T. atlanticus and T. zygis extracts showed the strongest anticoagulant activity. In contrast, Thymus satureioides did not show the anticoagulant activity in these tests. Conclusions: All aqueous extracts possess considerable antioxidant activity and are rich in total polyphenol and flavonoid but they act differently in the process of inflammatory and coagulation studied. This study shows great variability of biological activities in thyme varieties.
Johnsen, Søren Paaske; Svendsen, Marie Louise; Hansen, Morten Lock;
Preadmission oral anticoagulant treatment (OAT) has been linked with less severe stroke and a better outcome in patients with atrial fibrillation. However, the existing studies have methodological limitations and have, with one exception, not included hemorrhagic strokes. We performed a nationwid...... historic follow-up study using data from population-based healthcare registries to assess the effect of preadmission OAT on stroke outcomes further....
Kwa, Charlene Xian Wen; Tan, Veronique Kiak Mien; Ong, Hock Soo
We herein report the use of endoscopic n-butyl-2-cyanoacrylate injections to obliterate a gastric varix, which led to cyanoacrylate embolisation in the splenic and portal veins in a single patient. Cyanoacrylate embolisation is a known but uncommonly reported complication of endoscopic sclerotherapy. This case report illustrates the successful management of this complication (i.e. cyanoacrylate embolisation in the splenic and portal veins) with anticoagulation and analyses the presentation an...
Luca Masotti; Cecilia Becattini; Roberto Cappelli; Giancarlo Landini; Alessandro Pampana; Domenico Prisco; Giancarlo Agnelli
One of the main innovation emerged in recent years in the field of venous thromboembolism (VTE) has been represented by the clinical development and marketing of new oral anticoagulant agents used for prophylaxis and acute treatment. These drugs are represented by direct thrombin inhibitors (anti-factor IIa) and the direct inhibitors of activated factor X (anti-Xa). The main achievement of these new agents is represented by their ease of use without laboratory monitoring or dose adjustment. D...
Omer F. Karatas
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.
Elmeros, M.; Christensen, T. K.; Lassen, P.
We analyzed anticoagulant rodenticides (ARs) in birds of prey, owls and small mustelids to assess exposure rates and levels in Denmark. ARs were detected in 84-97% of individuals in all species. High AR prevalences and concentrations were recorded in all seasons in both birds and mammals. Prevalence of ARs was considerably higher than reported elsewhere with similar exposure scenarios. Further research on the potential effects of these high AR exposure levels on population levels of non-targe...
Dimova, Cena; Papakoca, Kiro; Kocev, Pavle; Milosev, Vladimir; Evrosimovska, Biljana
The individuals with implanted prosthetic heart valves (PHV) belong in the group of patients with high risk from several aspects. Medical risk assessment of these patients consists of three segments: 1. cardiac function and safe dental and oral surgery treatment, 2. existing risk of potential development and prevention from infective endocarditis, and 3. the potential for altered hemostasis in patients prescribed anticoagulant medications. The aim of this study was to show the specific or...
Brendan L Limone
Full Text Available OBJECTIVE: To conduct a systematic review of economic models of newer anticoagulants for stroke prevention in atrial fibrillation (SPAF. PATIENTS AND METHODS: We searched Medline, Embase, NHSEED and HTA databases and the Tuft's Registry from January 1, 2008 through October 10, 2012 to identify economic (Markov or discrete event simulation models of newer agents for SPAF. RESULTS: Eighteen models were identified. Each was based on a lone randomized trial/new agent, and these trials were clinically and methodologically heterogeneous. Dabigatran 150 mg, 110 mg and sequentially-dosed were assessed in 9, 8, and 9 models, rivaroxaban in 4 and apixaban in 4. Warfarin was a first-line comparator in 94% of models. Models were conducted from United States (44%, European (39% and Canadian (17% perspectives. Models typically assumed patients between 65-73 years old at moderate-risk of stroke initiated anticoagulation for/near a lifetime. All models reported cost/quality-adjusted life-year, 22% reported using a societal perspective, but none included indirect costs. Four models reported an incremental cost-effectiveness ratio (ICER for a newer anticoagulant (dabigatran 110 mg (n = 4/150 mg (n = 2; rivaroxaban (n = 1 vs. warfarin above commonly reported willingness-to-pay thresholds. ICERs vs. warfarin ranged from $3,547-$86,000 for dabigatran 150 mg, $20,713-$150,000 for dabigatran 110 mg, $4,084-$21,466 for sequentially-dosed dabigatran and $23,065-$57,470 for rivaroxaban. Apixaban was found economically-dominant to aspirin, and dominant or cost-effective ($11,400-$25,059 vs. warfarin. Indirect comparisons from 3 models suggested conflicting comparative cost-effectiveness results. CONCLUSIONS: Cost-effectiveness models frequently found newer anticoagulants cost-effective, but the lack of head-to-head trials and the heterogeneous characteristics of underlying trials and modeling methods make it difficult to determine the most cost-effective agent.
Austin, T.; Kalra, D.; Lea, N C; Patterson, D. L.; Ingram, D.
OBJECTIVES: This paper reports an evaluation of the properties of a generic electronic health record information model that were actually required and used when importing an existing clinical application into a generic EHR repository. METHOD: A generic EHR repository and system were developed as part of the EU Projects Synapses and SynEx. A Web application to support the management of anticoagulation therapy was developed to interface to the EHR system, and deployed within a north London hosp...
Geduhn, Anke; Jacob, Jens; Schenke, Detlef; Keller, Barbara; Kleinschmidt, Sven; Esther, Alexandra
Anticoagulant rodenticides (ARs) are commonly used to control rodent infestations for biocidal and plant protection purposes. This can lead to AR exposure of non-target small mammals and their predators, which is known from several regions of the world. However, drivers of exposure variation are usually not known. To identify environmental drivers of AR exposure in non-targets we analyzed 331 liver samples of red foxes (Vulpes vulpes) for residues of eight ARs and used local parameters (perce...
D. S. Zapryanova
Full Text Available Dynamics of the content in the goats’ blood (at the instant the sample was taken, and then after 3, 6 and 24 hours under influence of 4 anticoagulants (sodium fluoride, sodium citrate, heparin and complexon III were studied. Long term storage of the blood samples resulted in the glucose level decrease. It was mostly pronounced under the sodium citrate treatment.
Drozd, N N; Tolstenkov, A S; Makarov, V A; Kuznetsova, T A; Besednova, N N; Shevchenko, N M; Zvyagintseva, T N
Fucoidans isolated from Fucus evanescens and Laminaria cichorioides kelp can inhibit thrombin and factor Xa of the blood coagulation system. In rats, intravenous injection of fucoidans dose-dependently increased anticoagulant activity of the plasma. Fucoidans can form complexes with protamine sulfate. The observed quantitative differences in the action of fucoidans can result from different sulfation degree and the presence of various types of glycoside bonds in polysaccharide molecules. PMID:17415470
Full Text Available OBJECTIVE: To compare the effects of antiplatelets and anticoagulants on stroke and death in patients with acute cervical artery dissection. DESIGN: Systematic review with Bayesian meta-analysis. DATA SOURCES: The reviewers searched MEDLINE and EMBASE from inception to November 2012, checked reference lists, and contacted authors. STUDY SELECTION: Studies were eligible if they were randomised, quasi-randomised or observational comparisons of antiplatelets and anticoagulants in patients with cervical artery dissection. DATA EXTRACTION: Data were extracted by one reviewer and checked by another. Bayesian techniques were used to appropriately account for studies with scarce event data and imbalances in the size of comparison groups. DATA SYNTHESIS: Thirty-seven studies (1991 patients were included. We found no randomised trial. The primary analysis revealed a large treatment effect in favour of antiplatelets for preventing the primary composite outcome of ischaemic stroke, intracranial haemorrhage or death within the first 3 months after treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63, while the degree of between-study heterogeneity was moderate (τ(2 = 0.18. In an analysis restricted to studies of higher methodological quality, the possible advantage of antiplatelets over anticoagulants was less obvious than in the main analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30. CONCLUSION: In view of these results and the safety advantages, easier usage and lower cost of antiplatelets, we conclude that antiplatelets should be given precedence over anticoagulants as a first line treatment in patients with cervical artery dissection unless results of an adequately powered randomised trial suggest the opposite.
Kaliyamoorthy Kalidasan; Velayudham Ravi; Sunil Kumar Sahu; Murugan Lakshmi Maheshwaran; Kathiresan Kandasamy
Objective: To study the spine structure of stingray Himantura imbricata (H. imbricata) and to evaluate the anticoagulant properties of the spine extract obtained through various solvents extracts followed by antibacterial activity against human pathogens. Methods: Spines of H. imbricata were collected from Nagappattinam coast, Tamil Nadu, India and their spines were observed under the light microscope. The grounded spines were subjected to extraction of metabolites using m...
Walker, Lee A.; Anthony TURK; Long, Sara M.; Wienburg, Claire L.; Best, Jennifer; Shore, Richard F.
Secondary exposure of vertebrate predators to second-generation anticoagulant rodenticides (SGARs) is widespread in Britain. Tawny owl (Strix aluco) populations in the UK have declined since the 1970s, when SGARs were first introduced, and these compounds may have contributed to the decline in owl numbers. Our aims were to conduct the first systematic survey of SGAR exposure in tawny owls and ascertain whether there had been a change in the proportion of exposed birds that was concurrent wi...
Mantero, F; Procidano, M.; Vicariotto, M. A.; Girolami, A.
In patients receiving long-term acenocoumarin treatment, the effect on anticoagulant activity of atenolol (100 mg once-daily) and metoprolol (100 mg twice daily) was compared in a randomised within-patient open trial. No significant differences were demonstrated between mean prothrombin time and Thrombotest during treatment with atenolol, metoprolol or placebo. These data do not suggest the existence of an interaction between acenocoumarin and the moderately lipophilic β-adrenoceptor blocker ...
Claes, Neree; Moeremans, K; Buntinx, F.; Arnout, J; Vermylen, J.; H. van Loon; Annemans, L.
OBJECTIVES: A clinical trial, "Belgian Improvement Study on Oral Anticoagulation Therapy (BISOAT)," significantly improved the quality after implementing four different quality-improving interventions in four randomly divided groups of general practitioners (GPs). The quality-improving interventions consisted of multifaceted education with or without feedback reports on their performance, international normalized ratio (INR) testing by the GP with a CoaguChek device or computer-assisted advic...
Brooks, J. E.; Htun, P. T.; Naing, H.
The baseline susceptibility of the lesser bandicoot rat, Bandicota bengalensis, from Rangoon, Burma, to five anticoagulant rodenticides was established with no-choice feeding in the laboratory. The susceptibility of lesser bandicoots to the several poisons (brodifacoum, difenacoum, diphacinone, coumatetralyl, and warfarin) was such that they were offered at a 0.001% concentration. B. bengalensis was most susceptible to brodifacoum, and in descending order, difenacoum, coumatetralyl, diphacino...
Rowe, F. P.; Plant, C. J.; Bradfield, A.
Laboratory and field trials were conducted to determine the efficacy of the anticoagulant rodenticide bromadiolone against the house mouse (Mus musculus). In laboratory feeding tests, family groups of warfarin-resistant mice maintained in pens and conditioned to feeding on plain foods were offered pinhead oatmeal bait containing bromadiolone at 0.005%. Overall mortality in replicated 21-day poison treatments was 55/58 or 94.8%. Six field trials were carried out, using the same poison bait, ag...
Witeska, Malgorzata; WARGOCKA, Wioleta
Disodium EDTA used as anticoagulant for common carp blood caused a significant increase and high variability in hematocrit readings comparing to the heparinized samples. Na2EDTA induced erythrocyte swelling, causing cell membrane disruption (hemolysis). The nuclei released from destroyed cells changed shape from oval to round, and underwent gradual swelling and vacuolation, followed by karyolysis. The degree of observed changes was similar at all Na2EDTA concentrations (0.1, 0.5, and 1.0 mg/m...
Lesley J. Smith
Full Text Available Clotting blood contains fibrin-bound thrombin, which is a major source of procoagulant activity leading to clot extension and further activation of coagulation. When bound to fibrin, thrombin is protected from inhibition by antithrombin (AT + heparin but is neutralized when AT and heparin are covalently linked (ATH. Here, we report the surprising observation that, rather than yielding an inert complex, thrombin-ATH formation converts clots into anticoagulant surfaces that effectively catalyze inhibition of thrombin in the surrounding environment.
Preston, Roger J S
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.
Preston, Roger J S
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.
Andrew D Blann, Chee W KhooUniversity Department of Medicine, City Hospital, Birmingham, UKAbstract: As the risk factors for thrombosis are becoming better understood, so is the need for anticoagulation. The inherent difficulties with warfarin are such that a low-molecular-weight heparin (LMWH) is often the key therapeutic. However, there are several different species of LMWH available to the practitioner, which leads to the need for an objective guide. New agents are coming onto the...
Adiguzel Cafer; Fareed Jawed; Thethi Indermohan
Abstract Background The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of antic...
Yangcheng, Hanyu; Blanco, Michael; Gardner, Candice; Li, Xuehong; Jane, Jay-Lin
The objective of this study was to understand dosage effects of the Waxy gene on the structures of amylose and amylopectin and on the properties of corn starch. Reciprocal crossing of isogenic normal and waxy corn lines was conducted to develop hybrids with different dosages (0, 1, 2, 3) of Waxy gene in the endosperm. The amylose content of starch and proportions of branch chains of DP 17-30 and extra-long branch chains (DP>100) of amylopectin were positively correlated with the Waxy-gene dosage. Proportions of short (DPstarch were negatively correlated with the Waxy-gene dosage, indicating that amylose facilitated dissociation of the surrounding crystalline regions. These results helped us understand the function of granule-bound starch synthase I in the biosynthesis of amylose and amylopectin and impacts of Waxy-gene dosages on the properties of corn starch. PMID:27261752
The gelatin was irradiated for 0-60 kGy dosages by 60Co γ-ray. The relationship of dosage and properties including viscosity, gel strength, mechanical property, molecular weight and protein component was discussed. The results show that there is a negative correlation between the dosage and intrinsic viscosity, relative viscosity, gel strength and molecular weight. With the increase of irradiation dosage, the γ, β, α chain content of gelatin decreases but the small molecules content increases, and relative molecular weight distribution changes wider. The elongation decreases but tensile strength of gelatin film increases. Compared with no irradiation one, the irradiation gelatin has more compact and smooth surface texture. It is assumed that when the limited water and oxygen exist during the irradiation process, cross-linking and degradation of gelatin molecular produce simultaneously and the main reaction is cross-linking. The reaction degree increases with the dosage. (authors)
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.
Atterby, Helen; Kerins, Gerard M; MacNicoll, Alan D
The present study investigated the whole-carcass residue carried by resistant and susceptible laboratory rat strains following 5, 10, or 20 d of feeding on a diet of 25 mg difenacoum/kg bait. The mean whole-carcass residue of difenacoum was determined by high-performance liquid chromatography to be between 0.52 and 0.74 mg/kg body weight in all three rat strains tested. These values were considerably lower than some comparable data previously reported for other species and second-generation rodenticides as well as from mathematical models. The whole-carcass residue of extractable (i.e., nonrefractory) parent compound carried by highly resistant rats fed for 20 d (0.74 mg/kg body wt) is unlikely to present a significantly increased risk to predators compared to the amount carried by susceptible rats after 5 d of feeding (0.52 mg/kg body wt). However, resistant rats are more likely to be available for predation and to be carrying a whole-carcass residue of anticoagulant throughout the duration of a control program. PMID:15719991
Yang, Jie; Wang, Yuanhong; Jiang, Tingfu; Lv, Lv; Zhang, Boyuan; Lv, Zhihua
A controlled Cu(2+) catalytic free-radical depolymerization process of fucosylated chondroitin sulfate from sea cucumber Apostichopus japonicus was established. The results showed a good linear relationship between 1/Mw and time during the depolymerization. A series of fractions with different molecular weight were obtained, and the physicochemical properties of them were investigated and compared utilizing the chemical method, IR spectra and NMR spectra. The results showed no significant variations of the backbone and branches structures during the depolymerization. Furthermore, the anticoagulant activities of the depolymerized fractions were evaluated by the activated partial thromboplastin time (APTT). The APTT decreases in proportion to the molecular weight following a linear relationship and the prolongation of APTT activity requires at least oligosaccharide of 4 trisaccharide units (about 4000 Da). Their anticoagulant activity of low molecular weight fraction (Mw = 24,755 Da) is similar to LMWH with significantly less bleeding risk. The results suggest that the low molecular weight fraction could be used as a novel anticoagulant with less undesired side effects. PMID:25260572
Cai, Weirong; Xu, Huiling; Xie, Liangliang; Sun, Jian; Sun, Taotao; Wu, Xiaoyan; Fu, Qinbao
Three water-soluble polysaccharide fractions (GSP-1, GSP-2 and GSP-3) were obtained from Gentiana scabra Bunge roots by DEAE-Sepharose CL-6B and Sepharose CL-6B column chromatography. Their chemical characterizations were determined by high performance gel permeation chromatography (HPGPC), high performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) and Fourier transform infrared (FT-IR) spectrometer. Moreover, their in vitro anticoagulant activities were evaluated by activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays. GSP-1 and GSP-2 were composed of rhamnose, arabinose, galactose, glucose and galacturonic acid, while GSP-3 consisted of rhamnose, arabinose, galactose and galacturonic acid with a weight-average molecular weight of 5.8×10(4)Da. In comparison with the control group (saline), GSP, GSP-1, GSP-2 and GSP-3 could prolong APTT and TT, but not PT. Overall, GSP-3 exhibited potent anticoagulant activity and would be expected to be a potential source of anticoagulant. PMID:26876858
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
Aaron B. Holley
Full Text Available Introduction. Controversy remains over the optimal length of anticoagulation following idiopathic venous thromboembolism. We sought to determine if a longer, finite course of anticoagulation offered additional benefit over a short course in the initial treatment of the first episode of idiopathic venous thromboembolism. Data Extraction. Rates of deep venous thrombosis, pulmonary embolism, combined venous thromboembolism, major bleeding, and mortality were extracted from prospective trials enrolling patients with first time, idiopathic venous thromboembolism. Data was pooled using random effects meta-regression. Results. Ten trials, with a total of 3225 patients, met inclusion criteria. For each additional month of initial anticoagulation, once therapy was stopped, recurrent venous thromboembolism (0.03 (95% CI: −0.28 to 0.35; =.24, mortality (−0.10 (95% CI: −0.24 to 0.04; =.15, and major bleeding (−0.01 (95% CI: −0.05 to 0.02; =.44 rates measured in percent per patient years, did not significantly change. Conclusions: Patients with an initial idiopathic venous thromboembolism should be treated with 3 to 6 months of secondary prophylaxis with vitamin K antagonists. At that time, a decision between continuing with indefinite therapy can be made, but there is no benefit to a longer (but finite course of therapy.
Link, Mark S; Haïssaguerre, Michel; Natale, Andrea
Atrial fibrillation (AF) is the most common arrhythmia encountered by cardiologists and is a major cause of morbidity and mortality. Risk factors for AF include age, male sex, genetic predisposition, hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, heart failure, and possibly excessive exercise. The management of AF involves decisions about rate versus rhythm control. Asymptomatic patients are generally managed with rate control and anticoagulation. Symptomatic patients will desire rhythm control. Rhythm control options are either antiarrhythmic agents or ablation, with each having its own risks and benefits. Ablation of AF has evolved from a rare and complex procedure to a common electrophysiological technique. Selection of patients to undergo ablation is an important aspect of AF care. Patients with the highest success rates of ablation are those with normal structural hearts and paroxysmal AF, although those with congestive heart failure have the greatest potential benefit of the procedure. Although pulmonary vein isolation of any means/energy source is the approach generally agreed on for those with paroxysmal AF, optimal techniques for the ablation of nonparoxysmal AF are not yet clear. Anticoagulation reduces thromboembolic complications; the newer anticoagulants have eased management for both the patient and the cardiologist. Aggressive management of modifiable risk factors (hypertension, diabetes mellitus, sleep apnea, obesity, excessive alcohol, smoking, hyperthyroidism, pulmonary disease, air pollution, and possibly excessive exercise) after ablation reduces the odds of recurrent AF and is an important element of care. PMID:27462054
Miesbach, Wolfgang; Seifried, Erhard
To date, clinical studies show that the incidence of spontaneous bleeding with new direct oral anticoagulants (DOAs) is comparable to that of established anticoagulants. However, unlike vitamin K antagonists, there are currently no clinically available antidotes or approved reversal agents for new DOAs. Restoring normal coagulation is important in many cases, such as emergency surgeries, serious bleedings, or anticoagulant overdosing. Attempts have been made to restore normal coagulation after treatment with new DOAs using compounds such as recombinant activated factor VII (rFVIIa), prothrombin complex concentrate (PCC), or FEIBA (factor eight inhibitor bypassing activity). Limited pre-clinical data and even less clinical evidence are available on the usefulness of these methods in restoring normal coagulation for the emergency management of critical bleeding episodes. Evaluating the utility of DOAs is further complicated by the fact that it is unknown how predictive established test systems are of the bleeding risks. Clinical practice requires further evaluation of the emergency management options for the new DOAs to define the agents and the doses that are most useful. Furthermore, patients receiving long-term treatment with a DOA are likely to undergo elective surgery at some point, and there is lack of evidence regarding perioperative treatment regimens under such conditions. This review summarises potential bleeding management options and available data on the new DOAs. PMID:22782297
Full Text Available Ji Wang, Chengchu Zhu Department of Cardiothoracic Surgery, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China Abstract: Hypercoagulable state and disorganized angiogenesis are two conspicuous characteristics during tumor progression. There are a considerable number of clinical trials focusing on the effects of anticoagulant and antiangiogenic drugs on the survival of cancer patients. Favorable outcomes have been observed. Excessive blood coagulation not only causes cancer-associated thrombosis, which is a common complication and is the second leading cause of death in patients, but also decreases intratumoral perfusion rates and drug delivery by reducing the effective cross-sectional area of blood vessels. Meanwhile, structural and functional abnormalities of the tumor microvasculature also compromise convective drug transport and create a hypoxic and acidic microenvironment. Vascular normalization strategy can temporarily recover the abnormal state of tumor vasculature by improving blood density, dilation, and leakiness, resulting in enhanced penetration of chemotherapies and oxygen within a short time window. In this article, we first review the evidence to support the opinion that anticoagulant and antiangiogenic therapy can improve cancer survival through several underlying mechanisms. Next, we speculate on the feasibility and value of the combined strategy and discuss whether such a combination has a synergistic antineoplastic effect in cancer patients by way of increasing blood vessel perfusion and drug distribution. Keywords: tumor microenvironment, anticoagulation, antiangiogenesis, vascular normalization, tumor perfusion
Nagai, Mirei; Iwasaki, Kiyotaka; Umezu, Mitsuo; Ozaki, Makoto
Thrombogenic reactions under multiple interactions of pharmacological agents, doses, and materials have not been well understood yet. The aim of this study was to investigate the ability to simultaneously compare thrombogenic reactions to different combinations of anticoagulants, doses, and blood-contacting materials, in a single human blood using an in vitro test method. Four venous blood samples were drawn from each of six healthy volunteers into syringes that contained two different amounts of heparin and argatroban to set the activated clotting time (ACT) to approximately 200 or 500 s, respectively. The four blood samples from each volunteer were immediately poured into two clinical-grade extracorporeal circulation tubes: a polyvinyl chloride (PVC) tube and a poly(2-methoxyethyl acrylate)-coated (PMEA) PVC tube. These tubes with an inner diameter of 12.7 mm were rotated at 183 rpm in a 37°C chamber for 10 min. The results indicated that the in vitro thrombogenicity test method was capable of assessing differences in platelet factor 4 and β-thromboglobulin increases among different combinations of the two materials, two anticoagulants, and two ACTs. Higher amounts of total plasma proteins were absorbed on PVC tubes than on PMEA-coated tubes when using the same anticoagulant and dose. These data elucidate that the in vitro thrombogenicity test method is useful for the simultaneous quantitative evaluation of the influences of various combinations of materials, pharmacological agents, and doses on thrombogenicity in a single human blood. PMID:24652689
Vandenbroucke, V; Bousquet-Melou, A; De Backer, P; Croubels, S
The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one-half the lethal dose 50 (LD(50)), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC-ESI-MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half-lives in plasma for first-generation rodenticides were shorter than those for second-generation rodenticides. Coumatetralyl, a first-generation product, had a plasma elimination half-life of 0.52 days. Brodifacoum, a second-generation product, showed a plasma elimination half-life of 91.7 days. The elimination half-lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning. PMID:19000263
Chalermchaikit, T; Felice, L J; Murphy, M J
A liquid chromatographic method was developed for the analysis of indandione and 4-hydroxycoumarin anticoagulant rodenticides in blood serum and liver. The method enabled the measurement of serum and liver concentrations of eight anticoagulant rodenticides: brodifacoum, bromadiolone, chlorophacinone, coumafuryl, coumatetralyl, diphacinone, difenacoum, and warfarin. Anticoagulants were extracted from serum and liver with acetonitrile. Extracts were applied to solid-phase extraction columns, which contained mixed packings. Column eluates were evaporated to dryness, reconstituted, and subjected to reversed-phase liquid chromatography. Hydroxycoumarins were detected by fluorescence at an excitation wavelength of 318 nm and an emission wavelength of 390 nm. Indandiones were detected by UV absorption at 285 nm. Extraction efficiencies of greater than 75% for serum and greater than 69% for liver were obtained. The within-run precision (CV) ranged from 2.4 to 8.6% for serum and 2.6 to 8.7% for liver. The between-run precision (CV) ranged from 1.5 to 12.2% for serum and from 2.1 to 11.8% for liver. Hydroxycoumarin rodenticides were detected at 1 ng/mL of serum and 1 ng/g of liver. Indandiones were detected at 10 ng/mL of serum and 10 ng/g of liver. PMID:8429630