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Sample records for anticoagulation therapy mr-tomographische

  1. Anticoagulation therapy.

    PubMed

    Ginsberg, J A; Crowther, M A; White, R H; Ortel, T L

    2001-01-01

    Despite refinements and standardization in the use of anticoagulants, many problems remain for clinicians. Dr. Crowther describes appropriate starting and maintenance doses of warfarin, factors accounting for inter- and intra-observer variability and importantly, the management of the over-anticoagulated patients and bleeding patients. Dr. White compares unfractionated heparin (UFH) and low molecular weight heparin (LMWH) and addresses whether there truly are differences in the efficacy and safety of different LMWH's for both arterial and venous indications. Dr. Ortel discusses the management of the problem patient who requires anticoagulants, the management of heparin-induced thrombocytopenia, the pregnant patient, the obese patient, patients who have renal insufficiency and/or liver disease, patients with malignant disease, and other challenging patient populations.

  2. Oral Anticoagulant Therapy

    PubMed Central

    Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

    2012-01-01

    Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

  3. Anticoagulant therapy in pediatrics

    PubMed Central

    Dabbous, Mariam K.; Sakr, Fouad R.; Malaeb, Diana N.

    2014-01-01

    Thromboembolic episodes are disorders encountered in both children and adults, but relatively more common in adults. However, the occurrence of venous thromboembolism and use of anticoagulants in pediatrics are increasing. Unfractionated Heparin (UH) is used as a treatment and prevention of thrombosis in adults and critically ill children. Heparin utilization in pediatric is limited by many factors and the most important ones are Heparin Induced Thrombocytopenia (HIT) and anaphylaxis. However, Low Molecular Weight Heparin (LMWH) appears to be an effective and safe alternative treatment. Hence, it is preferred over than UH due to favorable pharmacokinetic and side effect profile. Direct Thrombin Inhibitors (DTI) is a promising class over the other anticoagulants since it offers potential advantages. The aim of this review is to discuss the differences between adult and pediatric thromboembolism and to review the current anticoagulants in terms of pharmacological action, doses, drug reactions, pharmacokinetics, interactions, and parameters. This review also highlights the differences between old and new anticoagulant therapy in pediatrics. PMID:25031496

  4. The evolution of anticoagulant therapy

    PubMed Central

    Franchini, Massimo; Liumbruno, Giancarlo M.; Bonfanti, Carlo; Lippi, Giuseppe

    2016-01-01

    Arterial and venous thromboembolism are leading causes of morbidity and mortality around the world. For almost 70 years, heparins (unfractionated heparin and low molecular weight heparins) and vitamin K antagonists have been the leading therapeutic medical options for the treatment and prevention of thromboembolic disorders. Nevertheless, the many limitations of these traditional anticoagulants have fuelled the search for novel agents over the past 15 years, and a new class of oral anticoagulants that specifically target activated factor X and thrombin has been developed and is now commercially available. In this narrative review, the evolution of anticoagulant therapy is summarised, with a focus on newer oral anticoagulants. PMID:26710352

  5. Infected renal hematoma complicating anticoagulant therapy.

    PubMed

    Morduchowicz, G; Rabinovitz, M; Neuman, M; Pitlik, S

    1987-03-01

    We describe a case of spontaneous infection of a renal hematoma complicating warfarin sodium anticoagulant therapy. The infected hematoma was successfully drained by sonar-guided fine-needle aspiration. All reported cases of renal hematomas complicating anticoagulant therapy are reviewed.

  6. Macroscopic hematuria in patients on anticoagulation therapy

    PubMed Central

    Mariyanovski, Valeri; Hadzhiyska, Valeria

    2015-01-01

    Introduction Visible hematuria is not rare in patients on anticoagulant therapy. There is no consensus regarding the diagnostic approach for them; some authors suggest restricted volume of diagnostic procedures because of the low number of urological etiology found. Some antibiotics have been reported to potentiate the effect of oral anticoagulants. Material and methods The study addresses the need for urological assessment of patients on anticoagulation therapy and the possible role of some drugs administrated simultaneously with an oral anticoagulant, for the onset of macroscopic hematuria. Patients hospitalized with hematuria, both with or without anticoagulation therapy, were investigated and followed up. Results The onset of hematuria depends on the monitoring of oral anticoagulation. INR (International Normalized Ratio) value corresponds with the probability of non-urological etiology, where INR>4 carries relatively low risk for urological and malignant etiology. Some antibiotics may influence the anticoagulation effect, so INR value may be elevated and hematuria may occur. Conclusions Anticoagulation therapy should be administrated carefully and individually. The risk of urological etiology of hematuria is lower in patients on oral anticoagulants (especially when INR >4), however, it is not zero. PMID:26568876

  7. Anticoagulant Therapy-Induced Gallbladder Hemorrhage after Cardiac Valve Replacement

    PubMed Central

    Cho, Seong Ho; Lee, Hae Young; Kim, Hyun Su

    2015-01-01

    Anticoagulation therapy is essential after cardiac valve surgery. However, spontaneous bleeding remains a major concern during anticoagulation therapy. Spontaneous gallbladder (GB) hemorrhage (hemobilia) is a rare occurrence during standard anticoagulation therapy. This report presents a case of GB hemorrhage that occurred shortly after initiating oral anticoagulant therapy in a patient who had undergone mitral valve replacement surgery. PMID:26665115

  8. Laboratory studies on patients receiving anticoagulant therapy

    PubMed Central

    Shaw, S.; Pegrum, G. D.; Wolff, S.

    1965-01-01

    An investigation into the laboratory control of anticoagulant therapy is presented. The cases were divided into those in the first few weeks of therapy and those on long-term treatment. Variations in the levels of factors VII and X, and factor IX were assessed. Thromboplastin levels were used to control therapy. These were compared with parallel estimations by Thrombotest and with the levels of the coagulation factors. Thrombotest was found to have no major advantage over thromboplastin. PMID:14304246

  9. Delivery of Optimized Inpatient Anticoagulation Therapy: Consensus Statement from the Anticoagulation Forum

    PubMed Central

    Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A

    2013-01-01

    Objective To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients. The guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. Study Selection and Data Extraction Because of this document’s scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent consensus opinion of all authors and are endorsed by the Board of Directors of The Anticoagulation Forum, a organization dedicated to optimizing anticoagulation care. The Board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. Data Synthesis Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in eight key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education (7) care transitions, (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. Conclusions Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national

  10. Contraindications to Anticoagulation Therapy and Eligibility for Novel Anticoagulants in Older Patients With Atrial Fibrillation

    PubMed Central

    Steinberg, Benjamin A.; Greiner, Melissa A.; Hammill, Bradley G.; Curtis, Lesley H.; Benjamin, Emelia J.; Heckbert, Susan R.; Piccini, Jonathan P.

    2015-01-01

    Aims Oral anticoagulation therapy prevents stroke and improves survival in patients with atrial fibrillation, but the therapy is underutilized. We sought to identify the prevalence of contraindications for oral anticoagulation and the proportion of patients potentially eligible for different agents. Methods We identified patients with nonacute atrial fibrillation in a nationally representative 5% sample of 2009 Medicare data. We divided the population into patients ineligible for any oral anticoagulant, patients eligible for warfarin only, and patients eligible for any anticoagulant. We compared patient characteristics and the use of anticoagulation among the subgroups. Results Among 86,671 patients with atrial fibrillation, 1872 (2.2%) were ineligible for anticoagulation because of an absolute contraindication, most frequently a history of intracranial hemorrhage (60%). Patients ineligible for any anticoagulant were the same age as the overall group (mean age, 80.5 vs 80.4 years). However, they had higher rates of dementia (19% vs 8.6%) and heart failure (59% vs 43%) and higher mean CHADS2 scores (3.8 vs 2.8). Of the remaining 84,799 patients eligible for anticoagulation, 7146 (8.4%) had were eligible for warfarin only (most commonly because of mechanical heart valves [66%] and end-stage renal disease [12%]). Sixty-five percent of patients eligible for anticoagulation received warfarin, and the proportion was similar for patients with a relatively high risk of bleeding. Conclusions Older adults with atrial fibrillation rarely have absolute contraindications to oral anticoagulation therapy. Among patients without contraindications, most appeared to be eligible for any anticoagulant, and relatively high-risk features appeared not to influence warfarin use. PMID:25930214

  11. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients.

    PubMed

    Alings, Marco

    2016-08-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations. PMID:27617088

  12. [Progress of anticoagulation therapy in atrial fibrillation].

    PubMed

    Hernández Olmedo, Miguel; Suárez Fernández, Carmen

    2015-08-01

    Atrial fibrillation is currently a very prevalent disease and it represents one of the most common causes of disabling stroke. Antithrombotic therapies have reduced the incidence of this complication although they pose many limitations and difficulties. As a result, a large number of high risk patients do not receive an appropriate treatment. In recent years, four new oral anticoagulants (NOAC) with relevant advantages in comparison to vitaminK antagonists have been released. Four large phaseiii clinical trials have demonstrated that NOAC are at least as safe and efficacious as warfarin in stroke prevention in non-valve atrial fibrillation patients with moderate-high thrombotic risk, being their main advantage the reduction in intracranial hemorrhage. The arrival of these drugs has caused great expectations in the management of these patients but also new doubts. Lacking data in some subgroups of frail patients, the absence of specific antidotes available and specially their high cost represent nowadays the main limitations for their generalization.

  13. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

    PubMed Central

    2016-01-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations. PMID:27617088

  14. Individualising Anticoagulant Therapy in Atrial Fibrillation Patients

    PubMed Central

    2016-01-01

    Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have emerged as alternatives to VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation. Four NOACS: dabigatran, apixaban, rivaroxaban and edoxaban, have received regulatory approval in Europe from the European Medicines Agency. Numerous factors can influence the decision to prescribe a NOAC, the most important of which are assessment of stroke and bleeding risks. Given the variation in design of the pivotal phase III clinical trials investigating the efficacy and safety of NOACs, and in the absence of head-to-head comparative data, it is impossible to recommend one NOAC over the other. However, NOACS offer the opportunity for individualised therapy based on factors such as renal function, age or patient/doctor preference for once- or twice-daily dosing regimens. Dose reduction of some NOACS should be considered in at-risk patient populations.

  15. Sudden sensorineural hearing loss during oral anticoagulant therapy.

    PubMed

    Mierzwa, Kathleen; Schneider, Gerlind; Müller, Andreas

    2004-11-01

    This study investigated the role of sudden sensorineural hearing loss (SSNHL) as a symptom in oral anticoagulant therapy with vitamin K antagonists (Phenprocoumon; Marcumar, Falithrom). Vascular compromise of the cochlea due to thrombosis, embolus, reduced blood flow or vasospasm is one of the four possible pathways that can lead to SSNHL. Oral anticoagulant therapy should prevent thrombosis; if it does not the question arises as to whether the anticoagulation is working, or the wrong hypothesis of vascular compromise has been made. Patients with SSNHL during oral anticoagulant therapy who were admitted to the ENT Department of the University Hospital in Jena from 1998 to 2001 were included. The pure-tone audiograms and the prothrombin time (PT) values before and after the event of the SSNHL were evaluated. The study found 10 patients with SSNHL during oral anticoagulant therapy. Although the audiograms showed some improvement in the majority of cases, three cases showed almost no improvement in hearing. On admission, half of the patients showed a PT-value higher than 30 per cent and in nine cases a PT-value >30 per cent could be demonstrated at least once during testing. It was not possible to demonstrate a relationship between the SSNHL and oral anticoagulation. Vascular compromise cannot be excluded as a cause for sudden hearing loss in patients undergoing oral anticoagulant therapy. It is possible that oral anticoagulants influence the viscosity of the plasma leading to interference with the microcirculation in the inner ear. Further research into this area is currently being conducted.

  16. [Duration of anticoagulant therapy in venous thromboembolic complications].

    PubMed

    Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A

    2016-01-01

    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.

  17. [Duration of anticoagulant therapy in venous thromboembolic complications].

    PubMed

    Kuznetsov, M R; Leontyev, S G; Neskhodimov, L A; Tolstikhin, V Yu; Khotinskiy, A A

    2016-01-01

    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

  18. Contemporary anticoagulation therapy in patients undergoing percutaneous intervention.

    PubMed

    Bhatty, Shaun; Ali, Asghar; Shetty, Ranjith; Sumption, Kevin F; Topaz, On; Jovin, Ion S

    2014-04-01

    The proper use of anticoagulants is crucial for ensuring optimal patient outcomes post percutaneous interventions in the cardiac catheterization laboratory. Anticoagulant agents such as unfractionated heparin, a thrombin inhibitor; low-molecular weight heparins, predominantly Factor Xa inhibitors; fondaparinux, a Factor Xa inhibitor and bivalirudin, a direct thrombin inhibitor have been developed to target various steps in the coagulation cascade to prevent formation of thrombin. Optimal anticoagulation achieves the correct balance between thrombosis and bleeding and is related to optimal outcomes with minimal complications. This review will discuss the mechanisms and appropriate use of current and emerging anticoagulant therapies used during percutaneous interventions.

  19. Contemporary anticoagulation therapy in patients undergoing percutaneous intervention.

    PubMed

    Bhatty, Shaun; Ali, Asghar; Shetty, Ranjith; Sumption, Kevin F; Topaz, On; Jovin, Ion S

    2014-04-01

    The proper use of anticoagulants is crucial for ensuring optimal patient outcomes post percutaneous interventions in the cardiac catheterization laboratory. Anticoagulant agents such as unfractionated heparin, a thrombin inhibitor; low-molecular weight heparins, predominantly Factor Xa inhibitors; fondaparinux, a Factor Xa inhibitor and bivalirudin, a direct thrombin inhibitor have been developed to target various steps in the coagulation cascade to prevent formation of thrombin. Optimal anticoagulation achieves the correct balance between thrombosis and bleeding and is related to optimal outcomes with minimal complications. This review will discuss the mechanisms and appropriate use of current and emerging anticoagulant therapies used during percutaneous interventions. PMID:24506409

  20. Physician's Fear of Anticoagulant Therapy in Nonvalvular Atrial Fibrillation

    PubMed Central

    Dahlberg, Katherine Willett

    2014-01-01

    Abstract: Despite the availability of predictive tools and treatment guidelines, anticoagulant therapies are underprescribed and many patients are undertreated for conditions that predispose to thromboembolic complications, including stroke. This review explores reasons for which physicians fear that the risks of anticoagulation may be greater than the potential benefit. The results of numerous clinical trials confirm that patients benefit from judiciously managed anticoagulation and that physicians can take various approaches to minimize risk. Use of stratification scores for patient selection and accurate estimation of stroke risk may improve outcomes; bleeding risk is less important than stroke risk. Adoption of newer anticoagulants with simpler regimens may help physicians allay their fears of anticoagulant use in patients with atrial fibrillation. These fears, although not groundless, should not overtake caution and hinder the delivery of appropriate evidence-based care. PMID:25285512

  1. Monitoring anticoagulant therapy with new oral agents.

    PubMed

    Ramos-Esquivel, Allan

    2015-12-26

    Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281

  2. [Heparin induced thrombocytopenia and anticoagulation in renal replacemant therapy].

    PubMed

    Steinfeldt, Thorsten; Rolfes, Caroline

    2008-04-01

    The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

  3. [Intramural hematoma of the ileum complicating anticoagulant therapy].

    PubMed

    Acea Nebril, B; Sánchez González, F; Aguirrezabalaga González, J; Crespo García, C; Lago Novoa, M; Blanco Freire, N

    1994-07-01

    The development of abdominal pain in the patient receiving anticoagulant therapy is more likely to pose a diagnostic dilemma. A group of intra-abdominal bleeding syndromes, which are extremely rare in patients with normal haemostasis, have been described in patients on anticoagulant therapy. Theses syndromes are of particular interest to surgeons because they simulate acute surgical conditions of the abdomen. We herein report the preoperative diagnosis of a spontaneous intramural hematoma of the small bowel by computed tomography. The authors conclude that CT should be used early in the diagnostic evaluation of abdominal pain and of acute abdomen in patients receiving anticoagulant therapy. Indications for the operative management of these patients include active bleeding, pneumoperitoneum, failure to improve with conservative management within 72 hours, worsening of symptoms, and uncertain diagnosis.

  4. Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics.

    PubMed

    Beitelshees, Amber L; Voora, Deepak; Lewis, Joshua P

    2015-01-01

    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 anticoagulation therapy. However, several factors may limit its usefulness and should be considered. PMID:25897256

  5. Application of the theory of planned behavior to oral anticoagulant therapy.

    PubMed

    Burns, Sharita

    2009-03-01

    Anticoagulation control is imperative for individuals who are prescribed long-term oral anticoagulation therapy. Therapeutic international normalized ratios decrease the risk of the thromboembolic complications that are associated with oral anticoagulation therapy. Individuals on oral anticoagulation therapy are often asked to make lifestyle modifications that can become barriers to medication adherence. The application of the theory of planned behavior to oral anticoagulation therapy can be used to assist advanced practice nurses in assessing individuals for the perceived barriers or obstacles that might interfere with the behavioral changes necessary to successfully comply with the recommended treatment plan. PMID:19298315

  6. Emerging anticoagulant therapies for atrial fibrillation: new options, new challenges.

    PubMed

    Mangiafico, R A; Mangiafico, M

    2012-01-01

    Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with an increased risk of stroke and systemic embolism. Oral anticoagulation with vitamin K antagonists (VKAs), such as warfarin, has historically been the mainstay of long-term thromboprophylaxis in AF patients. However, although highly effective, VKAs have a number of limitations that make their use difficult and cumbersome in clinical practice. They have a slow onset and offset of action, narrow therapeutic window, marked dose-response variability, and multiple food and drug interactions, and require frequent coagulation monitoring and dose adjustments. To overcome VKA drawbacks, several new oral anticoagulants have been recently developed for use in AF, and three of them, the direct thrombin inhibitor dabigatran etexilate and the direct factor Xa inhibitors rivaroxaban and apixaban, have completed phase III trials. New agents have proven to be noninferior or superior to warfarin for AF-related stroke prevention, with similar or better safety profiles. These new drugs, with their predictable anticoagulant effect that allows for fixed dosing with no need for coagulation monitoring, have the potential to greatly simplify anticoagulation therapy for AF. Dabigatran etexilate and rivaroxaban are already approved in the United States and Europe for stroke prevention in nonvalvular AF, and dabigatran etexilate has entered current AF guidelines as an alternative to warfarin. However, some issues with new compounds are still unresolved, such as the lack of antidotes and standardized tests to measure drug activity. Active postmarketing monitoring surveillance of effectiveness and safety is required in the implementation of new anticoagulant therapies. PMID:22830344

  7. Pharmacogenomics of Anti-platelet and Anti-coagulation Therapy

    PubMed Central

    Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.

    2013-01-01

    Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323

  8. [Anticoagulant therapy clinic: moving towards Advanced Nursing Practice].

    PubMed

    Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva

    2014-01-01

    There is currently around one million people receiving oral anticoagulants in Spain. The drug most used is acenocoumarol, which requires coagulation monitoring to ensure that the patient is within its normal therapeutic range. Patients usually start this treatment in a hospital clinic and, when they are stabilised, they are referred to primary care, where they are followed-up by their community nurses. The usual practice is that nurses are responsible for changes in the dose when the patients are outside the range. This practice is not performed by hospital nurses, despite having sufficient experience and knowledge to adequately manage these types of patients. An Advanced Nursing Practice model has been introduced into the Haematology management unit of the Hospital Universitario Virgen de la Victoria, Málaga. This involves various aspects of attention and care of patients on anticoagulant therapy, and includes adjusting the doses of their treatment following a catalogue of therapeutic and diagnostic ranges.

  9. [Bilateral renal infarction after discontinuation of anticoagulant therapy].

    PubMed

    Lavoignet, Charles-Éric; Le Borgne, Pierrick; Ugé, Sarah; Veneziano, Rinaldo; Brunhuber, Claudia; Kam, Claire; Bilbault, Pascal

    2016-07-01

    Acute renal infarction is an uncommon and often under diagnosed condition mostly because of misleading symptoms. Accurate data regarding clinical presentation, laboratory tests, diagnostic and treatment are lacking. Detection is often delayed or missed because of non-specific clinical presentation. The mechanisms of acute renal infarction are various, mainly embolic or thrombotic. Abdominal CT scan remains the most valuable exam to confirm the diagnosis. Therapeutic guidelines for the treatment of renal embolism have not been well established. The standard treatment strategy includes anticoagulation with or without thrombolysis. Despite the uncertainty regarding management, the renal outcome remains favorable. Some patients do develop some degree of renal insufficiency during the acute episode. We report here the case of a 73-year-old woman with bilateral acute renal infarction after discontinuation of anticoagulant therapy.

  10. [Anticoagulant therapy in secondary prevention of coronary events].

    PubMed

    Bultas, Jan

    2014-12-01

    Secondary prevention of atherothrombotic events is the domain of antiplatelet therapy and according to present risk is used one drug strategy or combination of acetylsalicylic acid with ADP receptor blockers. The importance of the combination of dual antiplatelet therapy together with xabans or dabigatran was investigated in 6 clinical trials. Only one of them (ATLAS ACS 2-TIMI 51) indicated that treatment with small dose of rivaroxaban (2 × 2.5 mg) may be added to dual strategy of acetylsalicylic acid and clopidogrel. The risk of major bleeding event is increased and net clinical benefit is only about 0.5 % per year. Dual therapy with aspirin and prasugrel or tikagrelor is beneficial. In the second part of the review is discussed higher incidence of myocardial infarction in controlled group in the trial comparing treatment of dabigatran with warfarin. This relationship has not been resolved, however, in patients with higher risk of coronary events and indication of anticoagulant treatment with direct oral anticoagulants it is recommended to choose from xabans (apixaban and rivaroxaban). PMID:25692828

  11. Anticoagulant and Antiplatelet Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease

    PubMed Central

    Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus

    2012-01-01

    Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation. PMID:22577538

  12. [Removal of an epidural catheter from a patient receiving anticoagulant and antiplatelet therapy].

    PubMed

    Arnal, D; Anduezaa, A; García del Valle, S

    2009-04-01

    We describe the management of anticoagulant and antiplatelet therapy to reduce the risk of hematoma on removal of an epidural catheter. The situation arose following major vascular surgery complicated by an acute myocardial infarction that required anticoagulant and antiplatelet therapy following implantation of a coronary stent.

  13. Sex Differences in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

    PubMed Central

    Blanco-Molina, Angeles; Enea, Iolanda; Gadelha, Telma; Tufano, Antonella; Bura-Riviere, Alessandra; Di Micco, Pierpaolo; Bounameaux, Henri; González, José; Villalta, Jaume; Monreal, Manuel

    2014-01-01

    Abstract In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex. As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant. In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice. PMID:25398066

  14. Pathophysiological basis for anticoagulant and antithrombotic therapy in pulmonary hypertension.

    PubMed

    Lopes, Antonio Augusto

    2006-01-01

    In pulmonary hypertension (PH), thrombosis and thromboembolism may occur as primary events associated with inherited or acquired thrombophilia. Alternatively, in situ thrombosis may develop as a complication of pre-existing vasculopathy as in the case of idiopathic PH and related disorders (so called pulmonary arterial hypertension). In these disorders, a number of abnormalities has been described involving endothelial cells, platelets and other circulating cellular and soluble elements. These abnormalities are suggestive of a shift of pulmonary vascular microenvironment toward a procoagulant, prothrombotic and antifibrinolytic pattern. The abnormalities described so far include circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P-selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and cytokines. Also, decreased endothelial production of natural anticoagulants (thrombomodulin) and platelet antiaggregating substances (nitric oxide, prostacyclin) have been demonstrated. The present review is focused on the procoagulant, prothrombotic and antifibrinolytic mechanisms so far identified in PH, in both clinical setting and animal models. Understanding of these mechanisms is crucial for a proper selection of anticoagulant and antithrombotic therapies and provides the rationale for development of novel therapeutic options.

  15. Effectiveness of Inferior Vena Cava Filters without Anticoagulation Therapy for Prophylaxis of Recurrent Pulmonary Embolism

    PubMed Central

    Zektser, Miri; Bartal, Carmi; Zeller, Lior; Nevzorov, Roman; Jotkowitz, Alan; Stavi, Vered; Romanyuk, Vitaly; Chudakov, Gregory; Barski, Leonid

    2016-01-01

    Objective The optimal treatment of deep vein thrombosis (DVT) is anticoagulation therapy. Inferior vena cava filter (IVC) placement is another option for the prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This is used mostly in patients with a contraindication to anticoagulant therapy. The purpose of the present study was to compare the two options. Methods A retrospective cohort study of two groups of patients with DVT: patients who received an IVC filter and did not receive anticoagulation due to contraindications; and patients with DVT and similar burden of comorbidity treated with anticoagulation without IVC insertion. To adjust for a potential misbalance in baseline characteristics between the two groups, we performed matching for age, gender, and Charlson’s index, which is used to compute the burden of comorbid conditions. The primary outcome was an occurrence of a PE. Results We studied 1,742 patients hospitalized with the diagnosis of DVT in our hospital;93 patients from this population received IVC filters. Charlson’s score index was significantly higher in the IVC filter group compared with the anticoagulation group. After matching of the groups of patients according to Charlson’s score index there were no significant differences in primary outcomes. Conclusion Inferior vena cava filter without anticoagulation may be an alternative option for prevention of PE in patients with contraindications to anticoagulant therapy. PMID:27487310

  16. [Improvements in oral anticoagulant therapy for atrial fibrillation].

    PubMed

    Briongos Figuero, Sem; García Santos-Gallego, Carlos; Badimón, Juan José

    2013-12-01

    For the last decades vitamin K antagonists have been the most effective anticoagulant treatment of atrial fibrillation. New molecules are being designed, mainly due to the great amount of disadvantages in the management of conventional anticoagulation. Dabigatran, rivaroxaban and apixaban will soon be available as an alternative to warfarin/acenocumarol. All of them have demonstrated to be non-inferior to warfarin in preventing stroke and systemic embolism, with even dabigatran 150 mg bid and apixaban being superior. They have also a lower risk of bleeding, especially regarding severe/fatal and intracranial hemorrhages. This is a real revolution. The advance of these new anticoagulants will be limited only by the higher cost, and will progressively become the protagonists of oral anticoagulation in patients with nonvalvular atrial fibrillation.

  17. Changing trends in anti-coagulant therapies. Are heparins and oral anti-coagulants challenged?

    PubMed

    Fareed, J; Iqbal, O; Cunanan, J; Demir, M; Wahi, R; Clarke, M; Adiguzel, C; Bick, R

    2008-06-01

    The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants and aspirin. Despite progress in the sciences, these drugs still remain a challenge and mystery. The development of low molecular weight heparins (LMWHS) and the synthesis of heparinomimetics represent a refined use of heparin. Additional drugs will continue to develop. However, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, GPIIb/IIIa inhibitors and other specific inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains the approach of choice to manage thrombotic disorders. The new anticoagulant targets, such as tissue factor, individual clotting factors, recombinant forms of serpins (antithrombin, heparin co-factor II and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin and site specific serine proteases inhibitors complexes have also been developed. There is a major thrust on the development of orally bioavailable anti-Xa and IIa agents, which are slated to replace oral anticoagulants. Both the anti-factor Xa and anti-IIa agents have been developed for oral use and have provided impressive clinical results. However, safety concerns related to liver enzyme elevations and thrombosis rebound have been reported with their use. For these reasons, the US Food and Drug Administration did not approve the orally active antithrombin agent Ximelagatran for several indications. The synthetic pentasaccharide (Fondaparinux) has undergone clinical development. Unexpectedly, Fondaparinux also produced major

  18. Control of anticoagulant and antiplatelet therapy. Managing patients with acute thrombotic disorders.

    PubMed Central

    Anderson, D. R.; Fernandez, L. A.

    1993-01-01

    Indications for using standard anticoagulants, heparin and warfarin; the dosage and route of administration; the importance of monitoring therapy with reliable laboratory indices; and complications of therapy are discussed. Acetylsalicylic acid and ticlopidine can be used as antiplatelet agents. Because their effect on platelet function is not monitored clinically, their clinical indications are emphasized. PMID:8495120

  19. Risk stratification, perioperative and periprocedural management of the patient receiving anticoagulant therapy.

    PubMed

    Oprea, Adriana D; Noto, Christopher J; Halaszynski, Thomas M

    2016-11-01

    As a result of the aging US population and the subsequent increase in the prevalence of coronary disease and atrial fibrillation, therapeutic use of anticoagulants has increased. Perioperative and periprocedural management of anticoagulated patients has become routine for anesthesiologists, who frequently mediate communication between the prescribing physician and the surgeon and assess the risks of both thromboembolic complications and hemorrhage. Data from randomized clinical trials on perioperative management of antithrombotic therapy are lacking. Therefore, clinical judgment is typically needed regarding decisions to continue, discontinue, bridge, or resume anticoagulation and regarding the time points when these events should occur in the perioperative period. In this review, we will discuss the most commonly used anticoagulants used in outpatient settings and discuss their management in the perioperative period. Special considerations for regional anesthesia and interventional pain procedures will also be reviewed. PMID:27687455

  20. 'Ins' and 'outs' of triple therapy: Optimal antiplatelet therapy in patients on chronic oral anticoagulation who need coronary stenting.

    PubMed

    Dewilde, W; Verheugt, F W A; Breet, N; Koolen, J J; Ten Berg, J M

    2010-09-01

    Chronic oral anticoagulant treatment is obligatory in patients (class I) with mechanical heart valves and in patients with atrial fibrillation with CHADS2 score >1. When these patients undergo percutaneous coronary intervention with placement of a stent, there is also an indication for treatment with aspirin and clopidogrel. Unfortunately, triple therapy is known to increase the bleeding risk. For this group of patients, the bottom line is to find the ideal therapy in patients with indications for both chronic anticoagulation therapy and percutaneous intervention to prevent thromboembolic complications such as stent thrombosis without increasing the risk of bleeding. (Neth Heart J 2010;18:444-50.).

  1. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

    PubMed

    Levine, Mark N; Raskob, Gary; Beyth, Rebecca J; Kearon, Clive; Schulman, Sam

    2004-09-01

    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 < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 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.

  2. Improving evidence on anticoagulant therapies for venous thromboembolism in children: key challenges and opportunities.

    PubMed

    Goldenberg, Neil A; Takemoto, Clifford M; Yee, Donald L; Kittelson, John M; Massicotte, M Patricia

    2015-12-10

    Venous thromboembolism (VTE) is increasingly diagnosed in pediatric patients, and anticoagulant use in this population has become common, despite the absence of US Food and Drug Administration (FDA) approval for this indication. Guidelines for the use of anticoagulants in pediatrics are largely extrapolated from large randomized controlled trials (RCTs) in adults, smaller dose-finding and observational studies in children, and expert opinion. The recently FDA-approved direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban, provide potential advantages over oral vitamin K antagonists and subcutaneous low-molecular-weight heparins (LMWHs). However, key questions arise regarding their potential off-label clinical application in pediatric thromboembolic disease. In this Perspective, we provide background on the use of LMWHs such as enoxaparin as the mainstay of treatment of pediatric provoked VTE; identify key questions and challenges with regard to DOAC trials and future DOAC therapy in pediatric VTE; and discuss applicable lessons learned from the recent pilot/feasibility phase of a large multicenter RCT of anticoagulant duration in pediatric VTE. The challenges and lessons learned present opportunities to improve evidence for anticoagulant therapies in pediatric VTE through future clinical trials.

  3. Spontaneous Resolution of Chronic Subdural Haematoma in a Patient Receiving Anticoagulant Therapy.

    PubMed

    Ratre, Shailendra; Yadav, Yadram; Choudhary, Sushma; Parihar, Vijay

    2015-08-01

    Significant chronic subdural hematoma (CSDH) is usually a surgical emergency. Spontaneous resolution of CSDH has rarely been reported in the literature. We are reporting a case of spontaneous resolution of CSDH in a patient receiving anticoagulant therapy who had undergone mitral valve replacement surgery. PMID:27604441

  4. Improving warfarin anticoagulation therapy in a community health system.

    PubMed

    Pubentz, M J; Calcagno, D E; Teeters, J L

    1998-10-01

    An internal chart review of warfarin patients revealed a 44 percent complication rate resulting in higher treatment costs, and identified patient noncompliance, access to monitoring, and insufficient patient education as contributing factors. A warfarin usage guideline was created to assist physicians with warfarin management and subsequently the Anticoagulation Center (ACC) was established. To date over 950 patients have been managed through the ACC with therapeutic international normalized ratios an average of 82 percent of the time. Fewer bleeds and treatment failures have occurred in the ACC group, and a patient satisfaction survey revealed that ACC patients were very satisfied with their care more often than non-ACC patients. PMID:10185241

  5. How I treat patients with inherited bleeding disorders who need anticoagulant therapy

    PubMed Central

    Martin, Karlyn

    2016-01-01

    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

  6. [GASTROINTESTINAL COMPLICATIONS OF ANTICOAGULANT THERAPY IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION].

    PubMed

    Novikova, N A; Volovchenko, A N; Oldakovsky, V I

    2015-01-01

    Non-valvular atrial fibrillation is the most common cardiac source of emboli and cardioembolic stroke. Anticoagulants are recommended for preventing stroke in patients with non-valvular atrial fibrillation. Warfarin reduces the risk of stroke in patients with AF by approximately two-thirds. Several novel anticoagulants that can overcome the limitations of warfarin have been introduced in the market or are under development. The NOACs are at least as effective as warfarin for stroke prevention in AF. Bleeding complications, including gastrointestinal bleeding, are common complication of anticoagulant treatment. The NOACs therapy are associated with an increased risk of major gastrointestinal bleeding compared with warfarin, and dabigatran is associated with an increased risk of non-bleeding upper GI symptoms such as dyspepsia and heartburn. This review provides information on the safety and risks of using NOACs, methods of treatment of gastrointestinal complications events in patients with non-valvular atrial fibrillation. PMID:26817106

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

    PubMed Central

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

    2016-01-01

    Women receiving vitamin K antagonists (VKAs) require adequate contraception because of the potential for fetal complications. It is unknown whether the use of hormonal therapy, especially those containing estrogens, is associated with recurrent venous thromboembolism (VTE) during anticoagulation. Despite the absence of data, World Health Organization guidelines state that use of estrogen-containing contraceptives confers an “unacceptable health risk” during established anticoagulation for VTE. We compared the incidences of recurrent VTE and abnormal uterine bleeding with and without concomitant hormonal therapy in women aged <60 years who were receiving anticoagulation with rivaroxaban or enoxaparin/VKA for confirmed VTE. Incidence densities in percentage per year were computed for the on and off estrogen-containing or progestin-only therapy periods. Cox regression models were fitted, with hormonal therapy (on vs off) as a time-dependent variable to derive the hazard ratio (HR) for the effects on recurrent VTE and abnormal uterine bleeding. In total, 1888 women were included. VTE incidence densities on and off hormonal therapy were 3.7%/year and 4.7%/year (adjusted HR, 0.56; 95% confidence interval [CI], 0.23-1.39), respectively, and were 3.7%/year and 3.8%/year, respectively, for estrogen-containing and progestin-only therapy. The adjusted HR for all abnormal uterine bleeding (on vs off hormonal therapy) was 1.02 (95% CI, 0.66-1.57). Abnormal uterine bleeding occurred more frequently with rivaroxaban than with enoxaparin/VKA (HR, 2.13; 95% CI, 1.57-2.89). Hormonal therapy was not associated with an increased risk of recurrent VTE in women receiving therapeutic anticoagulation. The observed increased risk of abnormal uterine bleeding with rivaroxaban needs further exploration. PMID:26696010

  8. [Quality of life of patients with venous thromboses in different variants of anticoagulant therapy].

    PubMed

    Kalinin, R E; Suchkov, I A; Pshennikov, A S; Agapov, A B

    2016-01-01

    The CIVIQ questionnaire was used to evaluate quality of life of patients presenting with deep vein thrombosis of lower limbs in different variants of anticoagulant therapy. The study included a total of 170 patients who were depending on the variant of anticoagulant therapy subdivided into 3 groups: Group One (comprising 48 patients) taking rivaroxaban as monotherapy; Group Two (consisting of 73 subjects) receiving low molecular weight heparin (enoxaparin sodium) followed by adjusting the warfarin dose, and Group Three (including 49 patients) receiving low molecular weight heparin (enoxaparin sodium) followed by rivaroxaban. The total value of the level of quality of life in all groups showed a tendency towards restoration. However, patients taking warfarin during the follow-up period were found to have negative dynamics by the 6th month of treatment. It was revealed that quality of life on all parameters was higher in patients taking rivaroxaban and lower in those taking warfarin. The parameters of the physical component of health turned out to depend upon the degree of recanalization of the thrombus. After 6 months of anticoagulant therapy patients taking rivaroxaban (Groups One and Three) were found to have good recanalization in 87.5 and 87.7% of cases, respectively, while in Group Two being observed in 54.8% of patients only. Taking an anticoagulant at a fixed dose not requiring laboratory control (rivaroxaban) increases patient compliance, thus leading to improvement of both mental and social wellbeing.

  9. Preoperative percutaneous stone surgery in patients receiving anticoagulant therapy.

    PubMed

    Gross, Andreas J; Bach, T

    2009-10-01

    Percutaneous nephrostolithotomy (PCNL) is an essential component in the management of large volume renal calculi. Either in combination with shockwave lithotripsy but especially as monotherapy, PCNL is recommended as the most effective treatment option for patients with staghorn calculi or large volume stone disease. Multiple tracts allow successful management of nearly every stone burden in a single surgical session. Furthermore, patients with anatomic variations (eg, horseshoe kidney) can be treated by PCNL successfully. Overall stone-free rates of above 78% are described. With the rising age of the overall patient population, another problem occurs. Increasing age frequently leads to an increase in comorbidities; for example, patients receiving anticoagulation may need treatment for stones, which can pose a dilemma. The aim of this review was to provide an overview of thrombotic risk, depending on the underlying disease, and to propose a clinical pathway on how to deal with this selected group of patients.

  10. Risks and benefits of citrate anticoagulation for continuous renal replacement therapy.

    PubMed

    Shum, H P; Yan, W W; Chan, T M

    2015-04-01

    Heparin, despite its significant side-effects, is the most commonly used anticoagulant for continuous renal replacement therapy in critical care setting. In recent years, citrate has gained much popularity by improving continuous renal replacement therapy circuit survival and decreasing blood transfusion requirements. However, its complex metabolic consequences warrant modification in the design of the citrate-based continuous renal replacement therapy protocol. With thorough understanding of the therapeutic mechanism of citrate, a simple and practicable protocol can be devised. Citrate-based continuous renal replacement therapy can be safely and widely used in the clinical setting with appropriate clinical staff training.

  11. Curative effect of mechanical heart valve replacement and anticoagulant therapy after surgery.

    PubMed

    Chuai, J B; Shi, L; Ma, X Y; Wu, D; Kang, K; Jiang, S L

    2016-01-01

    This study was carried out to determine the curative effect of low-intensity anticoagulant therapy by observing the oral administration of warfarin (anticoagulant therapy) on patients who had undergone mechanical heart valve replacement (MHVR) surgery with subsequent anticoagulation complications. Fifty patients who underwent MHVR in the Second Affiliated Hospital of Harbin Medical University and 52 patients in the Cardiovascular Surgery of Daqing Oilfield General Hospital between January 2013 and January 2016 were selected (63 males and 39 females, ages 26-77 years). They took warfarin after treatment and were followed-up by means of outpatient review and telephone after leaving the hospital. The effect of warfarin and the occurrence of anticoagulation complications were analyzed. The operations lasted 230±106 min, extracorporeal circulation for 110±50 min and aorta occlusion for 82±23 min. During post-operation 3 patients developed skin purpura and one patient died. During follow-up we found 3 cases of anemia caused by excessive menstruation, 4 cases of hematuresis, 3 cases of peated epistaxis, 1 case of gastrointestinal bleeding, 1 case of cerebral hemorrhage, 1 case of embolism in the lower limbs and 1 case of cerebral infarction, although they all improved or were totally cured. Therefore, the incidence of complications can be reduced significantly by the correct administration of warfarin as well as timely monitoring of interference factors after MHVR. PMID:27049085

  12. Anticoagulant therapy for sepsis-associated disseminated intravascular coagulation: the view from Japan.

    PubMed

    Iba, T; Gando, S; Thachil, J

    2014-07-01

    The current management of disseminated intravascular coagulation (DIC) is based on aggressive treatment of the underlying condition and resuscitation with appropriate blood products. Anticoagulant therapy has appeared and disappeared in the different guidelines and important documents detailing the treatment of DIC. For example, Surviving Sepsis Campaign (SSC) guidelines, the 'global standard' for the management of severe sepsis, had recombinant activated protein C highly recommended in the original version, but this was withdrawn in the latest version due to the lack of evidence. In contrast, recent international guidance released from the International Society on Thrombosis and Haemostasis has introduced the potential efficacy of other agents. In sepsis-related DIC, the basis for anticoagulant therapy comes from the mounting evidence for the anti-inflammatory effects which these agents possess and can prove beneficial in septic situations. Several studies have clearly shown the important cross-talk between coagulation and inflammation in patients with sepsis. More recently, neutrophil extracellular traps and damage-associated molecular patterns (DAMPs), especially histones, have been demonstrated to play a crucial role in the coagulopathy of sepsis. Once again, the natural anticoagulants have an important function in neutralizing the effects of DAMPs and histones. In this review, in addition to examining the important role of anticoagulants in the septic milieu, the clinical studies examining antithrombin, recombinant thrombomodulin and plasma-derived activated protein C are detailed. However, large-scale randomized controlled trials are yet to be performed, with important consideration of the timing, dosage and duration of treatment.

  13. Fatal Events in Cancer Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

    PubMed Central

    Farge, Dominique; Trujillo-Santos, Javier; Debourdeau, Philippe; Bura-Riviere, Alessandra; Rodriguez-Beltrán, Eva Maria; Nieto, Jose Antonio; Peris, Maria Luisa; Zeltser, David; Mazzolai, Lucia; Hij, Adrian; Monreal, Manuel

    2015-01-01

    Abstract In cancer patients treated for venous thromboembolism (VTE), including deep-vein thrombosis (DVT) and pulmonary embolism (PE), analyzing mortality associated with recurrent VTE or major bleeding is needed to determine the optimal duration of anticoagulation. This was a cohort study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry database to compare rates of fatal recurrent PE and fatal bleeding in cancer patients receiving anticoagulation for VTE. As of January 2013, 44,794 patients were enrolled in RIETE, of whom 7911 (18%) had active cancer. During the course of anticoagulant therapy (mean, 181 ± 210 days), 178 cancer patients (4.3%) developed recurrent PE (5.5 per 100 patient-years; 95% CI: 4.8–6.4), 194 (4.7%) had recurrent DVT (6.2 per 100 patient-years; 95% confidence interval [CI]: 5.3–7.1), and 367 (8.9%) bled (11.3 per 100 patient-years; 95% CI: 10.2–12.5). Of 4125 patients initially presenting with PE, 43 (1.0%) died of recurrent PE and 45 (1.1%) of bleeding; of 3786 patients with DVT, 19 (0.5%) died of PE, and 55 (1.3%) of bleeding. During the first 3 months of anticoagulation, there were 59 (1.4%) fatal PE recurrences and 77 (1.9%) fatal bleeds. Beyond the third month, there were 3 fatal PE recurrences and 23 fatal bleeds. In RIETE cancer patients, the rate of fatal recurrent PE or fatal bleeding was much higher within the first 3 months of anticoagulation therapy. PMID:26266353

  14. Anticoagulant therapy of cancer patients: Will patient selection increase overall survival?

    PubMed

    Spek, C Arnold; Versteeg, Henri H; Borensztajn, Keren S

    2015-08-31

    Already since the early 1800s, it has been recognised that malignancies may provoke thromboembolic complications, and indeed cancer patients are at increased risk of developing venous thrombosis. Interestingly, case control studies of deep-vein thrombosis suggested that low-molecular-weight heparin (LMWH) improved survival of cancer patients. This led to the hypothesis that cancer cells might 'take advantage' of a hypercoagulable state to more efficiently metastasise. Initial randomised placebo control trials showed that LMWH improve overall survival of cancer patients, especially in those patients with a relatively good prognosis. The failure of recent phase III trials, however, tempers enthusiasm for anticoagulant treatment in cancer patients despite an overwhelming body of literature showing beneficial effects of anticoagulants in preclinical models. Instead of discarding LMWH as potential (co)treatment modality in cancer patients, these disappointing recent trials should guide future preclinical research on anticoagulants in cancer biology. Most and for all, the underlying mechanisms by which coagulation drives tumour progression need to be elucidated. This could ultimately allow selection of cancer patients most likely to benefit from anticoagulant treatment and/or from targeted therapy downstream of coagulation factor signalling.

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

    PubMed Central

    Jimson, S.; Amaldhas, Julius; Jimson, Sudha; Kannan, I.; Parthiban, J.

    2015-01-01

    Introduction: The risk of postoperative hemorrhage from oral surgical procedures has been a concern in the treatment of patients who are receiving long-term anticoagulation therapy. A study undertaken in our institution to address questions about the amount and severity of bleeding associated with minor outpatient oral surgery procedures by assessing bleeding in patients who did not alter their anticoagulant regimen. Subjects and Methods: Eighty-three patients receiving long-term anticoagulant therapy visited Department of Oral and Maxillofacial Surgery from May 2010 to October 2011 for extractions and minor oral surgical procedures. Each patient was required to undergo preoperative assessment of prothrombin time (PT) and measurement of the international normalized ratio. Fifty-six patients with preoperative PT values within the therapeutic range 3–4 were included in the study. The patients’ age ranged between 30 and 75 years. Application of surgispon was done following the procedure. Extraction of teeth performed with minimal trauma to the surrounding tissues, the socket margins sutured, and sutures removed after 5 days. Results: There was no significant incidence of prolonged or excessive hemorrhage and wound infection and the healing process was normal. PMID:26015691

  16. Long-Term Anticoagulant Therapy of Patients with Venous Thromboembolism. What Are the Practices?

    PubMed Central

    Mahé, Isabelle; Sterpu, Raluca; Bertoletti, Laurent; López-Jiménez, Luciano; Mellado Joan, Meritxell; Trujillo-Santos, Javier; Ballaz, Aitor; Hernández Blasco, Luis Manuel; Marchena, Pablo Javier; Monreal, Manuel

    2015-01-01

    Current guidelines of antithrombotic therapy suggest early initiation of vitamin K antagonists (VKA) in non-cancer patients with venous thromboembolism (VTE), and long-term therapy with low-molecular weight heparin (LMWH) for those with cancer. We used data from RIETE (international registry of patients with VTE) to report the use of long-term anticoagulant therapy over time and to identify predictors of anticoagulant choice (regarding international guidelines) in patients with- and without cancer. Among 35,280 patients without cancer, 82% received long-term VKA (but 17% started after the first week). Among 4,378 patients with cancer, 66% received long term LMWH as monotherapy. In patients without cancer, recent bleeding (odds ratio [OR] 2.70, 95% CI 2.26–3.23), age >70 years (OR 1.15, 95% CI 1.06–1.24), immobility (OR 2.06, 95% CI 1.93–2.19), renal insufficiency (OR 2.42, 95% CI 2.15–2.71) and anemia (OR 1.75, 95% CI 1.65–1.87) predicted poor adherence to guidelines. In those with cancer, anemia (OR 1.83, 95% CI 1.64–2.06), immobility (OR 1.51, 95% CI 1.30–1.76) and metastases (OR 3.22, 95% CI 2.87–3.61) predicted long-term LMWH therapy. In conclusion, we report practices of VTE therapy in real life and found that a significant proportion of patients did not receive the recommended treatment. The perceived increased risk for bleeding has an impact on anticoagulant treatment decision. PMID:26076483

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

    PubMed

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

    2015-10-01

    This study aimed to explore the correlation between usual vitamin K intake and response to anticoagulant therapy among patients under warfarin therapy. We conducted a retrospective survey of patients (n = 50) on continuous warfarin therapy. Clinical information and laboratory parameters were sourced from medical records. Anticoagulant effect was evaluated by using the percent time in therapeutic range (TTR) and the coefficient of variation (CV) of International normalized ratio (INR). Dietary vitamin K intake was assessed using a semi-quantitative food frequency questionnaire that has been developed for the purpose of assessing dietary intake of vitamin K. A total of 50 patients aged between 21 and 87 years were included in the study. The mean vitamin K intake was 262.8 ± 165.2 µg/day. Study subjects were divided into tertiles according to their usual vitamin K intake. The proportion of men was significantly higher in second and third tertile than first tertile (p = 0.028). The mean percent TTR was 38.4 ± 28.4% and CV of INR was 31.8 ± 11.8%. Long-term warfarin therapy group (≥ 3 years) had a higher percentage of TTR as compared to the control group (< 3 years) (p = 0.046). No statistically significant correlation was found between usual vitamin K intake and percent TTR (p > 0.05). In conclusion, no significant association was observed between usual vitamin K intake and anticoagulant effects. Further studies are required to consider inter-individual variability of vitamin K intake. Development of assessment tools to measure inter-individual variability of vitamin K intake might be helpful.

  18. Clinical review: anticoagulation for continuous renal replacement therapy--heparin or citrate?

    PubMed

    Oudemans-van Straaten, Heleen M; Kellum, John A; Bellomo, Rinaldo

    2011-01-24

    Heparin is the most commonly prescribed anticoagulant for continuous renal replacement therapy. There is, however, increasing evidence questioning its safety, particularly in the critically ill. Heparin mainly confers its anticoagulant effect by binding to antithrombin. Heparin binds to numerous other proteins and cells as well, however, compromising its efficacy and safety. Owing to antithrombin consumption and degradation, and to the binding of heparin to acute phase proteins, and to apoptotic and necrotic cells, critical illness confers heparin resistance. The nonspecific binding of heparin further leads to an unpredictable interference with inflammation pathways, microcirculation and phagocytotic clearance of dead cells, with possible deleterious consequences for patients with sepsis and systemic inflammation. Regional anticoagulation with citrate does not increase the patient's risk of bleeding. The benefits of citrate further include a longer or similar circuit life, and possibly better patient and kidney survival. This needs to be confirmed in larger randomized controlled multicenter trials. The use of citrate might be associated with less inflammation and has useful bio-energetic implications. Citrate can, however, with inadequate use cause metabolic derangements. Full advantages of citrate can only be realized if its risks are well controlled. These observations suggest a greater role for citrate.

  19. Do novel oral anticoagulants do better than standard therapy in the treatment of deep vein thrombosis?

    PubMed

    Brodmann, M

    2013-08-01

    The focus of DVT treatment is the prevention of recurrence and thrombus migration by treatment with anticoagulants. The aim is to improve outcomes by reducing clot burden and by preventing thrombus propagation, in order to prevent PE and the development of long-term complication. Actually, initial therapy is parenteral anticoagulation, mainly with low molecular weight heparin followed by a vitamin K antagonist (VKA) for triggered and idiopathic DVT. The long term treatment suggestion with a VKA is for sure the most challenging therapeutic scenario, showing all the disadvantages of VKA especially in the onset phase when therapeutic levels of VKA are difficult to achieve. The difference between VKAs and NOACs is the fact, that NOACs target a specific factor in the coagulation cascade. At time now two pathways have been chosen for treatment options, the direct inhibition of active sites of thrombin and factor Xa. Routine monitoring is not required and the drugs can be administered in fixed doses, which should increase patient adherence to long term treatment. At time now, four novel anticoagulants are called to be options for DVT treatment. Rivaroxaban, apixaban and edoxaban are direct FXa inhibitors, whereas dabigtran etexilate is a direct thrombin inhibitor. PMID:23681109

  20. [Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

    PubMed

    Ishikawa, Shinya; Kasai, Yoshitaka; Matsuura, Natsumi; Tarumi, Shintaro; Nakano, Jun; Okuda, Masaya; Goto, Masashi; Ryu, Dagu; Go, Tetsuhiko; Yokomise, Hiroyasu

    2015-04-01

    In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes. PMID:25836998

  1. Anticoagulant therapy for nodular regenerative hyperplasia in a HIV-infected patient

    PubMed Central

    2010-01-01

    Background Nodular regenerative hyperplasia (NRH) has been recently recognized as an emergent cause of liver disease in HIV-infected patients. NRH may cause non-cirrhotic portal hypertension with potentially severe consequences such as refractory ascites, variceal bleeding and hypersplenism. Obliteration of the small intrahepatic portal veins in association with prothrombotic disorders linked to HIV infection itself or anti-retroviral therapy seem to be the causes of NRH and thus the term HIV-associated obliterative portopathy has been proposed. Case Presentation Here we describe a case of a HIV-infected patient with biopsy-proven NRH and listed for liver transplantation (LT) because of refractory ascites and repeated upper gastrointestinal bleedings. A transjugular intrahepatic portosystemic shunt was placed as a bridge to LT and did not improve liver function. However, anticoagulant therapy with low-molecular-weight heparin (LMWH) was associated with rapid improvement in the liver condition and allowed to avoid LT in this patient. Conclusions Thus, this case underscores the relation between thrombophilia and HIV-associated NRH and emphasizes anticoagulant therapy as possible treatment. PMID:20082713

  2. Online Hemoglobin and Oxygen Saturation Sensing During Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

    PubMed

    Yessayan, Lenar T; Yee, Jerry; Frinak, Stan; Szamosfalvi, Balazs

    2015-01-01

    Optical hemoglobin and oxygen saturation sensor (OHOS) monitor when used in combination with other hemodynamic tools may be useful for continuous hemodynamic monitoring during ultrafiltration. The stand-alone OHOS monitor can easily be deployed predialyzer into the extracorporeal circuit of continuous renal replacement therapy (CRRT) systems. To maximize the accuracy of the OHOS in 24 hr CRRT systems, clotting in the optical blood chamber and the presensor dilution incurred by replacement fluid should be minimized. Sustained low-efficiency dialysis (SLED) with regional citrate anticoagulation is a therapy that incorporates an OHOS and maintains the overall reliability of hemoglobin (Hb) and saturation sensing. The system operates at a blood flow rate of 60 ml/min and a fixed acid citrate infusion rate of 150 ml/hr. The presensor dilution incurred by concentrated citrate infusion would result in a minimal Hb dilution (<0.7 g/dl) while minimizing optical blood chamber clotting during 24 hr SLED.

  3. Characteristics of Symptomatic Intracranial Hemorrhage in Patients Receiving Non-Vitamin K Antagonist Oral Anticoagulant Therapy

    PubMed Central

    2015-01-01

    Objectives The first non-vitamin K antagonist oral anticoagulant (NOAC) introduced to the market in Japan was dabigatran in March 2011, and three more NOACs, rivaroxaban, apixaban, and edoxaban, have since become available. Randomized controlled trials of NOACs have revealed that intracranial hemorrhage (ICH) occurs less frequently with NOACs compared with warfarin. However, the absolute incidence of ICH associated with NOACs has increased with greater use of these anticoagulants, and we wanted to explore the incidence, clinical characteristics, and treatment course of patients with NOACs-associated ICH. Methods We retrospectively analyzed the characteristics of symptomatic ICH patients receiving NOACs between March 2011 and September 2014. Results ICH occurred in 6 patients (5 men, 1 woman; mean ± SD age, 72.8 ± 3.2 years). Mean time to onset was 146.2 ± 111.5 days after starting NOACs. Five patients received rivaroxaban and 1 patient received apixaban. None received dabigatran or edoxaban. Notably, no hematoma expansion was observed within 24 h of onset in the absence of infusion of fresh frozen plasma, activated prothrombin complex concentrate, recombinant activated factor VIIa or hemodialysis. When NOAC therapy was initiated, mean HAS-BLED and PANWARDS scores were 1.5 ± 0.5 and 39.5 ± 7.7, respectively. Mean systolic blood pressure was 137.8 ± 15.9 mmHg within 1 month before spontaneous ICH onset. Conclusion Six symptomatic ICHs occurred early in NOAC therapy but hematoma volume was small and did not expand in the absence of infusion of reversal agents or hemodialysis. The occurrence of ICH during NOAC therapy is possible even when there is acceptable mean systolic blood pressure control (137.8 ± 15.9 mmHg) and HAS-BLED score ≤ 2. Even stricter blood pressure lowering and control within the acceptable range may be advisable to prevent ICH during NOAC therapy. PMID:26171862

  4. Discontinuation of Anticoagulant or Antiplatelet Therapy for Transrectal Ultrasound-Guided Prostate Biopsies: A Single-Center Experience

    PubMed Central

    Casey, Rowan G; Galvin, David J; Manecksha, Rustom P; Varadaraj, Haradikar; McDermott, TED; Grainger, Ronald; Lynch, Thomas H

    2012-01-01

    Purpose Historically, it was thought that hemorrhagic complications were increased with transrectal ultrasound-guided prostate biopsies (TRUS biopsy) of patients receiving anticoagulation/antiplatelet therapy. However, the current literature supports the continuation of anticoagulation/antiplatelet therapy without additional morbidity. We assessed our experience regarding the continuation of anticoagulation/antiplatelet therapy during TRUS biopsy. Materials and Methods A total of 91 and 98 patients were included in the anticoagulation/antiplatelet (group I) and control (group II) groups, respectively. Group I subgroups consisted of patients on monotherapy or dual therapy of aspirin, warfarin, clopidogrel, or low molecular weight heparin. The TRUS biopsy technique was standardized to 12 cores from the peripheral zones. Patients completed a questionnaire over the 7 days following TRUS biopsy. The questionnaire was designed to assess the presence of hematuria, rectal bleeding, and hematospermia. Development of rectal pain, fever, and emergency hospital admissions following TRUS biopsy were also recorded. Results The patients' mean age was 65 years (range, 52 to 74 years) and 63.5 years (range, 54 to 74 years) in groups I and II, respectively. The overall incidence of hematuria was 46% in group I compared with 63% in group II (p=0.018). The incidence of hematospermia was 6% and 10% in groups I and II, respectively. The incidence of rectal bleeding was similar in group I (40%) and group II (39%). Statistical analysis was conducted by using Fisher exact test. Conclusions There were fewer hematuria episodes in anticoagulation/antiplatelet patients. This study suggests that it is not necessary to discontinue anticoagulation/antiplatelet treatment before TRUS biopsy. PMID:22536465

  5. Optimizing adjunctive antithrombotic and anticoagulant therapy in primary PCI for STEMI.

    PubMed

    Deharo, Pierre; Rahbi, Hazim; Cuisset, Thomas

    2016-06-01

    The pharmacological management of patients with ST elevation myocardial infarction (STEMI) poses a significant challenge to the clinician. While mechanical reperfusion with primary percutaneous coronary intervention (PPCI) has proved its superiority over fibrinolysis, the best antithrombotic strategy surrounding the procedure remains a matter of debate. Due to the high risk of bleeding induced by antithrombotic drugs, the pharmacological management of STEMI needs to focus on an optimal strategy that reduces the rate of coronary thrombotic events without leading to excess bleeding. Intravenous anticoagulants are recommended for all patients presenting with STEMI. Low molecular heparin may be preferred over unfractionated heparin in the setting of PPCI. Recent data suggest that anticoagulation with bivalirudin can be utilized as an alternative strategy to heparin and Gp2b3a but this should be limited to patients at high risk of bleeding. Dual antiplatelet therapy comprising aspirin and P2Y12 inhibitor represents the cornerstone treatment for STEMI. New P2Y12 inhibitors (prasugrel and ticagrelor) have restricted clopidogrel use to situations where these potent agents are contraindicated. Whilst all oral antiplatelet agents have been used with an initial loading dose in STEMI, the time of their administration remains a controversial issue. In everyday practice, intravenous antiplatelet agents appear less consensual. While Gp2b3a receptor inhibitors use has been restricted to bailout situations, the place of cangrelor is not yet defined in real life daily practice.

  6. Perioperative management of patients receiving anticoagulant or antiplatelet therapy: a clinician-oriented and practical approach.

    PubMed

    Douketis, James D

    2011-10-01

    The management of patients who are receiving warfarin, aspirin, clopidogrel, or combinations of these drugs and require their interruption because of an elective surgical or other invasive procedure is a common and sometimes challenging clinical problem. For the practicing clinician, there are 2 key issues for perioperative anticoagulant management: 1) having an approach to stratify patients according to their risk for thromboembolism when warfarin or antiplatelet drug therapy is interrupted, and also having an approach to stratify patients according to the risk of bleeding associated with the surgery or procedure; and 2) determining which patients may require bridging anticoagulation and, if required, how to administer bridging, typically with a low-molecular-weight heparin, before and after surgery in a manner that minimizes the risk for bleeding. The overall goal is to minimize patients' risk for thromboembolism and bleeding throughout the perioperative period. The objective of this article is to provide an evidence-based but practical approach relating to these 2 key issues in a manner than can be applied to everyday clinical practice.

  7. Antiplatelet therapy strategies after percutaneous coronary intervention in patients needing oral anticoagulation.

    PubMed

    Saint Etienne, Christophe; Angoulvant, Denis; Simeon, Edouard; Fauchier, Laurent

    2013-11-01

    Long-term oral anticoagulant (OAC) and dual-antiplatelet therapy are commonly needed in patients with atrial fibrillation and in patients undergoing percutaneous coronary intervention (PCI), respectively. The combination of atrial fibrillation and PCI is frequent, and leads to a dilemma for antithrombotic therapy, where risk of stroke or stent thrombosis must be balanced with bleeding risk. In the WOEST study, 573 patients on OAC undergoing PCI were randomly assigned to receive clopidogrel alone or clopidogrel plus aspirin. The primary end point was the occurrence of any bleeding episode during 1-year follow-up. Clopidogrel alone administered to patients taking OAC after PCI was associated with a significantly lower rate of bleeding complications than clopidogrel plus aspirin. Moreover, a composite secondary end point of death, myocardial infarction and stent thrombosis was significantly lower in the dual-therapy group compared with the triple-therapy group. In spite of its limitations, the WOEST study constitutes a major breakthrough, showing that long-term aspirin after PCI may be obsolete in certain circumstances. This needs to be confirmed in further studies.

  8. A new plastic collection tube made of polyethylene terephtalate is suitable for monitoring traditional anticoagulant therapy (oral anticoagulant, unfractionated heparin, and low molecular weight heparin).

    PubMed

    Toulon, Pierre; Ajzenberg, Nadine; Smahi, Motalib; Guillin, Marie-Claude

    2007-01-01

    To improve the safety of blood collection, plastic tubes have been developed but various interactions with the coagulation system and/or antithrombotic drugs were reported with the first generation of such tubes. The aim of this multicentre study was to compare hemostasis test results measured in evacuated plastic tubes made of polyethylene terephtalate (VenoSafe, Terumo Europe) and in siliconized glass tubes containing the same citrate concentration (0.129 M). In addition, the impact of aging of the plastic tube was investigated by collecting blood samples in tubes at 8 months and at 1 month before expiry. Blood was drawn in 3 centres from untreated patients (n=269), patients on oral anticoagulant treatment (OAT, n=221), and patients treated with either unfractionated heparin (UFH, n=73) or a low molecular weight derivative (LMWH, n=48). Prothrombin time (PT) or INR, activated partial thromboplastin time (APTT) and anti-FXa activity were locally performed, when applicable. In untreated patients and in patients on OAT, PT and APTT values were found statistically shorter (p<0.05) when evaluated in plastic tubes than in glass tubes, except when PT was evaluated using a human thromboplastin. Surprisingly, significantly longer APTT and higher anti-FXa activities were obtained when blood from patients on UFH was drawn in plastic than in glass tubes. However, none of the differences had any clinical relevance (Bland-Altman analysis). In patients on anticoagulant treatment, there was no effect of aging of the plastic tubes. These results suggest that the plastic tube VenoSafe is suitable for coagulation testing both in untreated subjects and more interestingly in patients on traditional anticoagulant therapy during the whole shelf life indicated by the manufacturer. PMID:16426667

  9. A novel microfluidic anti-factor Xa assay device for monitoring anticoagulant therapy at the point-of-care

    NASA Astrophysics Data System (ADS)

    Harris, Leanne F.; Rainey, Paul; Castro-López, Vanessa; O'Donnell, James S.; Killard, Anthony J.

    2013-05-01

    Millions of patients worldwide are receiving anticoagulant therapy to treat hypercoagulable diseases. While standard testing is still performed in the central laboratory, point-of-care (POC) diagnostics are being developed due to the increasing number of patients requiring long-term anticoagulation and with a need for more personalized and targeted therapy. Many POC devices on the market focus on clot measurement, a technique which is limited in terms of variability, highlighting the need for more reliable assays of anticoagulant status. The anti-Xa assay, a factor specific optical assay, was developed to measure the extent to which exogenous factor Xa (FXa) is inhibited by heparinantithrombin complexes. We have developed a novel microfluidic device and assay for monitoring the effect of heparin anticoagulant therapy at the point-of-care. The assay which was also developed in our institute is based on the anti-Xa assay principle but uses fluorescence as the method of detection. Our device is a disposable laminate microfluidic strip, fabricated from the cyclic polyolefin (COP), Zeonor®, which is extremely suitable for application to fluorescent device platforms. We present data on the execution of the anti-Xa assay in this microfluidic format, demonstrating that the assay can be used to measure heparin in human plasma samples from 0 to 0.8 U/ml, with average assay reproducibility of 8% and a rapid result obtained within 60 seconds. Results indicate that with further development, the fluorogenic anti-Xa assay and device could become a successful method for monitoring anticoagulant therapy.

  10. Utilization of Anticoagulation Therapy in Medicare Patients with Nonvalvular Atrial Fibrillation

    PubMed Central

    Fitch, Kate; Broulette, Jonah; Pyenson, Bruce; Iwasaki, Kosuke; Kwong, Winghan Jacqueline

    2012-01-01

    Background Clinical guidelines recommend oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF) at moderate or high risk for stroke but not at high risk for bleeding; however, studies consistently report suboptimal use of such therapy. This study used Medicare Part D claims data to assess the use of warfarin in the Medicare population. Objectives To compare real-world warfarin utilization with current treatment guideline recommendations, and to assess the effect of warfarin exposure level on patient outcomes in Medicare beneficiaries with nonvalvular AF (NVAF). Methods Patients who were recently diagnosed with NVAF were identified using a random 5% sample of Research Identifiable Files of Medicare beneficiaries in 2006 or 2007. Individuals with moderate-to-high stroke risk per CHADS2 but not at high bleeding risk per ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleeding risk score were evaluated for warfarin use, as identified by the presence of ≥1 warfarin prescription claims within 12 months after the index diagnosis. Warfarin exposure level was assessed by the proportion of days covered during the 12-month follow-up period. The effect of warfarin exposure on ischemic stroke and major bleeding event rates during the 12-month follow-up period were assessed using multivariate logistic regression. Results Data from 14,149 newly diagnosed patients with NVAF (mean age, 79 years; 58.7% female) were analyzed, and of these, 7524 (53.2%) patients were identified as having moderate-to-high stroke risk and not being at high bleeding risk. Of these patients, 3110 (41.3%) did not receive warfarin within 12 months of the index diagnosis. The risk for ischemic stroke was significantly lower in those with warfarin exposure versus no warfarin exposure (adjusted odds ratio [OR], 0.51; confidence interval [CI], 0.43–0.61; P <.001) and in patients with warfarin proportion of days covered ≥80% versus those with proportion of days

  11. A Proposal for an Individualized Pharmacogenetic-Guided Warfarin Dosage Regimen for Puerto Rican Patients Commencing Anticoagulation Therapy

    PubMed Central

    Bosch, Luis Ángel Bermúdez

    2014-01-01

    Warfarin is the current standard of care in oral anticoagulation therapy. It is commonly prescribed to treat venous thromboembolism, pulmonary embolism, acute myocardial infarction, and to decrease the risk of stroke in atrial fibrillation. Warfarin therapy is challenging because of marked and often unpredictable inter-individual dosing variations that effectively reach and maintain adequate anticoagulation. Several researchers have developed pharmacogenetic-guided maintenance dose algorithms that incorporate genetics and individual patient characteristics. However, there is limited information available concerning dosing during warfarin initiation. This is considered the most clinically challenging therapeutic phase. In such, the risk of recurrent thromboembolism and hemorrhage are elevated. The objective of this retrospective study is to predict the individual initial doses for Puerto Rican patients (n=175) commencing anticoagulation therapy at Veterans Affairs Caribbean Healthcare System (VACHS) using pharmacogenetic/pharmacokinetic-driven model. A pharmacogenetic driven model (R2=0.4809) was developed in Puerto Rican patients and combined with pharmacokinetic formulas that enabled us to predict the individual initial doses for patients (n=121) commencing anticoagulation therapy. WinNonlin® pharmacokinetic-pharmacodynamic simulations were carried out to determine the predictability of this model. This model demonstrated promising results with few (n=10) simulations outside of their respective therapy range. A customized pharmacogenetic-based warfarin maintenance dose algorithm (R2=0.7659) was developed in a derivation cohort of 131 patients. The predictability of this developed pharmacogenetic algorithm was compared with the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm and it demonstrated superior predictability within our study population. PMID:25285240

  12. MOLECULAR MODELLING, 3D-QSAR, AND DRUG DOCKING STUDIES ON THE ROLE OF NATURAL ANTICOAGULANT COMPOUNDS IN ANTITHROMBOTIC THERAPY

    PubMed Central

    Kakarla, Prathusha; Devireddy, Amith R.; Inupakutika, Madhuri A.; Cheeti, Upender R.; Floyd, Jared T.; Mun, Mukherjee M.; Vigil, Raelyn N.; Hunter, Russell P.; Varela, Manuel F.

    2015-01-01

    Thromboembolic disorders are the leading cause of human mortality. Therefore, development of effective anticoagulant therapy is critical. Factor XIIIA (FXIIIA) protein is a crucial factor in the blood coagulation cascade, and hence it is a vital target for evolution of new antithrombotic agents. Structure-function studies of clotting factor active sites, clot formation, and thrombus structure have gained prominence in the efforts to develop novel anticoagulants. Factor XIIIA was homology modelled with the human transglutaminase-2 crystal structure as a base template for BLAST analysis. Docking and comparative binding site analysis revealed active site residue conservation and inhibitor-protein interactions. Nineteen small molecules possessing suspected anticoagulant properties were successfully docked into the FXIIIA active site following the best CoMFA and CoMSIA prediction values. Dabigatran etexilate was anticipated to be the best FXIIIA inhibitor among the nineteen anticoagulants with the highest binding affinity for the FXIIIA protein and the highest FlexX dock score of −29.8 KJ/mol. Structural properties of FXIIIA inhibitors with increased antithrombotic activity were predicted by this docking study. PMID:25750914

  13. Subacute stent thrombosis and the anticoagulation controversy: changes in drug therapy, operator technique, and the impact of intravascular ultrasound.

    PubMed

    Moussa, I; Di Mario, C; Di Francesco, L; Reimers, B; Blengino, S; Colombo, A

    1996-08-14

    Clinical trials have shown that stents are superior to other catheter-based coronary interventions in terms of reduced complications and improved long-term efficacy. With utilization of high-pressure balloon inflation and intravascular ultrasound (IVUS) guidance, stent implantation can now be performed safely without anticoagulation (i.e., with lower rates of stent thrombosis and vascular complications). In 2 recent prospective clinical trials, stent thrombosis occurred in 3.5% of cases despite anticoagulant therapy, which resulted in an average of 7% vascular and bleeding complications. Initial use of IVUS during traditional stent deployment showed that 80% of stents were underexpanded and led to the hypothesis that stent thrombosis might be decreased as a result of optimal stent placement under IVUS guidance without the need for anticoagulation. In a prospective clinical trial to test this hypothesis, three factors were found to reduce stent thrombosis: full stent expansion, complete apposition to the vessel wall, and full lesion coverage. Predictors of thrombotic risk in this era of high-pressure stent deployment without anticoagulation include low ejection fraction, residual dissections, slow flow, multiple stents per lesion, and smaller postprocedure stent luminal diameter. To optimize stent expansion, stent dilation should be performed using a mean inflation pressure of 18 atm with a noncompliant or minimally compliant balloon sized to the vessel being treated (B/V ratio = 1.1). Controversy still remains about the best poststent antiplatelet regimen, and results of a recent trial should indicate whether heparin coating provides additional protection from stent thrombosis.

  14. Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant

    PubMed Central

    Glueck, Charles J.; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

    2016-01-01

    Background: When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. Case Presentation: A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. Conclusion: When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation. PMID:27536705

  15. Whose preferences should be elicited for use in health-care decision-making? A case study using anticoagulant therapy.

    PubMed

    Mott, David John; Najafzadeh, Mehdi

    2016-01-01

    The question of whose preferences to elicit in health-state valuation has been widely discussed in the literature. The importance of this debate lies in the fact that health-state utility values are used in health technology assessment (HTA); therefore, an individual's preferences can influence decision-making. If preferences differ across groups, making decisions based on one group's preferences may be suboptimal for the other. Preferences for benefits, risks, experiences and health states associated with anticoagulant therapies have been elicited by researchers due to the underutilization of warfarin and the introduction of non-vitamin K antagonist oral anticoagulants. The majority of existing studies elicit preferences from patient populations as opposed to other stakeholders such as the general public. This paper extends the preference debate by using this clinical area as a case study, with a particular focus on HTA guidelines and the recent advocacy of the use of preference information in benefit-risk assessments. PMID:26560704

  16. Patients' perspectives on self-testing of oral anticoagulation therapy: Content analysis of patients' internet blogs

    PubMed Central

    2011-01-01

    Background Patients on oral anticoagulant therapy (OAT) require regular testing of the prothrombin time (PT) and the international normalised ratio (INR) to monitor their blood coagulation level to avoid complications of either over or under coagulation. PT/INR can be tested by a healthcare professional or by the patient. The latter mode of the testing is known as patient self-testing or home testing. The objective of this study was to elicit patients' perspectives and experiences regarding PT/INR self-testing using portable coagulometer devices. Methods Internet blog text mining was used to collect 246 blog postings by 108 patients, mainly from the USA and the UK. The content of these qualitative data were analysed using XSight and NVivo software packages. Results The key themes in relation to self-testing of OAT identified were as follows: Patient benefits reported were time saved, personal control, choice, travel reduction, cheaper testing, and peace of mind. Equipment issues included high costs, reliability, quality, and learning how to use the device. PT/INR issues focused on the frequency of testing, INR fluctuations and individual target (therapeutic) INR level. Other themes noted were INR testing at laboratories, the interactions with healthcare professionals in managing and testing OAT and insurance companies' involvement in acquiring the self-testing equipment. Social issues included the pain and stress of taking and testing for OAT. Conclusions Patients' blogs on PT/INR testing provide insightful information that can help in understanding the nature of the experiences and perspectives of patients on self-testing of OAT. The themes identified in this paper highlight the substantial complexities involved in self-testing programmes in the healthcare system. Thus, the issues elicited in this study are very valuable for all stakeholders involved in developing effective self-testing strategies in healthcare that are gaining considerable current momentum

  17. Endoscopy in patients on antiplatelet or anticoagulant therapy, including direct oral anticoagulants: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guidelines

    PubMed Central

    Veitch, Andrew M; Vanbiervliet, Geoffroy; Gershlick, Anthony H; Boustiere, Christian; Baglin, Trevor P; Smith, Lesley-Ann; Radaelli, Franco; Knight, Evelyn; Gralnek, Ian M; Hassan, Cesare; Dumonceau, Jean-Marc

    2016-01-01

    The risk of endoscopy in patients on antithrombotics depends on the risks of procedural haemorrhage versus thrombosis due to discontinuation of therapy. P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor) For low-risk endoscopic procedures we recommend continuing P2Y12 receptor antagonists as single or dual antiplatelet therapy (low quality evidence, strong recommendation); For high-risk endoscopic procedures in patients at low thrombotic risk, we recommend discontinuing P2Y12 receptor antagonists five days before the procedure (moderate quality evidence, strong recommendation). In patients on dual antiplatelet therapy, we suggest continuing aspirin (low quality evidence, weak recommendation). For high-risk endoscopic procedures in patients at high thrombotic risk, we recommend continuing aspirin and liaising with a cardiologist about the risk/benefit of discontinuation of P2Y12 receptor antagonists (high quality evidence, strong recommendation). Warfarin The advice for warfarin is fundamentally unchanged from British Society of Gastroenterology (BSG) 2008 guidance. Direct Oral Anticoagulants (DOAC) For low-risk endoscopic procedures we suggest omitting the morning dose of DOAC on the day of the procedure (very low quality evidence, weak recommendation); For high-risk endoscopic procedures, we recommend that the last dose of DOAC be taken ≥48 h before the procedure (very low quality evidence, strong recommendation). For patients on dabigatran with CrCl (or estimated glomerular filtration rate, eGFR) of 30–50 mL/min we recommend that the last dose of DOAC be taken 72 h before the procedure (very low quality evidence, strong recommendation). In any patient with rapidly deteriorating renal function a haematologist should be consulted (low quality evidence, strong recommendation). PMID:26873868

  18. Is stopping of anticoagulant therapy really required in a minor dental surgery? - How about in an endodontic microsurgery?

    PubMed Central

    Cho, Yong-Wook

    2013-01-01

    Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT) regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery. PMID:24010076

  19. Warfarin Anticoagulant Therapy: A Southern Italy Pharmacogenetics-Based Dosing Model

    PubMed Central

    Mazzaccara, Cristina; Conti, Valeria; Liguori, Rosario; Simeon, Vittorio; Toriello, Mario; Severini, Angelo; Perricone, Corrado; Meccariello, Alfonso; Meccariello, Pasquale; Vitale, Dino Franco; Filippelli, Amelia; Sacchetti, Lucia

    2013-01-01

    Background and Aim Warfarin is the most frequently prescribed anticoagulant worldwide. However, warfarin therapy is associated with a high risk of bleeding and thromboembolic events because of a large interindividual dose-response variability. We investigated the effect of genetic and non genetic factors on warfarin dosage in a South Italian population in the attempt to setup an algorithm easily applicable in the clinical practice. Materials and Methods A total of 266 patients from Southern Italy affected by cardiovascular diseases were enrolled and their clinical and anamnestic data recorded. All patients were genotyped for CYP2C9*2,*3, CYP4F2*3, VKORC1 -1639 G>A by the TaqMan assay and for variants VKORC1 1173 C>T and VKORC1 3730 G>A by denaturing high performance liquid chromatography and direct sequencing. The effect of genetic and not genetic factors on warfarin dose variability was tested by multiple linear regression analysis, and an algorithm based on our data was established and then validated by the Jackknife procedure. Results Warfarin dose variability was influenced, in decreasing order, by VKORC1-1639 G>A (29.7%), CYP2C9*3 (11.8%), age (8.5%), CYP2C9*2 (3.5%), gender (2.0%) and lastly CYP4F2*3 (1.7%); VKORC1 1173 C>T and VKORC1 3730 G>A exerted a slight effect (<1% each). Taken together, these factors accounted for 58.4% of the warfarin dose variability in our population. Data obtained with our algorithm significantly correlated with those predicted by the two online algorithms: Warfarin dosing and Pharmgkb (p<0.001; R2 = 0.805 and p<0.001; R2 = 0.773, respectively). Conclusions Our algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy. PMID:23990957

  20. Are there a guidelines for implantable spinal cord stimulator therapy in patients using chronic anticoagulation therapy? - A review of decision-making in the high-risk patient

    PubMed Central

    Ghaly, Ramsis F.; Lissounov, Alexei; Candido, Kenneth D.; Knezevic, Nebojsa Nick

    2016-01-01

    Background: Spinal cord stimulators (SCSs) are gaining increasing indications and utility in an expanding variety of clinical conditions. Complications and initial expenses have historically prevented the early use of SCS therapy despite ongoing efforts to educate and promote its utilization. At present, there exists no literature evidence of SCS implantation in a chronically anticoagulated patient, and neuromodulation manufacturers are conspicuously silent in providing warnings or recommendations in the face of anticoagulant use chronically. It would appear as through these issues demand scrutiny and industry as well as neuromodulation society advocacy and support in terms of the provision of coherent guidelines on how to proceed. Case Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Description: A 79-year-old male returned to the neurosurgical clinic with persistent low back pain and leg heaviness due to adjacent level degenerative spondylosis and severe thoracic spinal stenosis. The patient had a notable history of multiple comorbidities along with atrial fibrillation requiring chronic anticoagulation. On initial presentation, he was educated with three choice of conservative medical therapy, intrathecal drug delivery system implantation, or additional lumbar decompression laminectomy with instrumented fusion of T10-L3 and a palliative surgical lead SCS implantation. Conclusion: Our literature search did not reveal any

  1. The use of vitamin K in patients on anticoagulant therapy: a practical guide.

    PubMed

    Hanslik, Thomas; Prinseau, Jacques

    2004-01-01

    Anticoagulation with antivitamin K (AVK) is very effective for primary and secondary prevention of thromboembolic events. However, questions persist about the risks and management of over-anticoagulation. For reversal of excessive anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K administration, prothrombin complex or fresh frozen plasma may be used, depending on the excess of anticoagulation, the existence and site of active bleeding, patient characteristics and the indication for AVK. In over-anticoagulated patients, vitamin K aims at rapid lowering of the international normalized ratio (INR) into a safe range to reduce the risk of major bleeding and therefore improving patient outcome without exposing the patient to the risk of thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction to the medication. The risk of bleeding increases dramatically when the INR exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5 per 1000 per day. Patient characteristics, including advanced age, treated hypertension, history of stroke, and concomitant use of various drugs, affect the risk of bleeding. The absolute risk of thromboembolism associated with overcorrection appears to be in the same range as the risk of bleeding due to over-anticoagulation. The use of vitamin K in patients with warfarin over-anticoagulation lowers excessively elevated INR faster than withholding warfarin alone; however, it has not been clearly demonstrated that vitamin K treatment does, in fact, lower the risk of major hemorrhage. As vitamin K administration via the intravenous route may be complicated by anaphylactoid reactions, and via the subcutaneous route by cutaneous reactions, oral administration is preferred. A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg may be more appropriate. Overcorrection of the INR or

  2. Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

    PubMed

    Goto, Koji; Nakai, Kentaro; Shizuta, Satoshi; Morimoto, Takeshi; Shiomi, Hiroki; Natsuaki, Masahiro; Yahata, Mitsuhiko; Ota, Chihiro; Ono, Koh; Makiyama, Takeru; Nakagawa, Yoshihisa; Furukawa, Yutaka; Kadota, Kazushige; Takatsu, Yoshiki; Tamura, Takashi; Takizawa, Akinori; Inada, Tsukasa; Doi, Osamu; Nohara, Ryuji; Matsuda, Mitsuo; Takeda, Teruki; Kato, Masayuki; Shirotani, Manabu; Eizawa, Hiroshi; Ishii, Katsuhisa; Lee, Jong-Dae; Takahashi, Masaaki; Horie, Minoru; Takahashi, Mamoru; Miki, Shinji; Aoyama, Takeshi; Suwa, Satoru; Hamasaki, Shuichi; Ogawa, Hisao; Mitsudo, Kazuaki; Nobuyoshi, Masakiyo; Kita, Toru; Kimura, Takeshi

    2014-07-01

    The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ≥2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ≥65%. Cumulative 5-year incidence of stroke in patients with TTR ≥65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence.

  3. Current Perioperative Management of Anticoagulant and Antiplatelet Use in Neuroendovascular Therapy: Analysis of JR-NET1 and 2

    PubMed Central

    ENOMOTO, Yukiko; YOSHIMURA, Shinichi; SAKAI, Nobuyuki; EGASHIRA, Yusuke

    2014-01-01

    To evaluate current perioperative antithrombotic management in neuroendovascular therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in various procedures and examined their relationships with periprocedural adverse events. Patient's data from nationwide surveys administered by the Japanese Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December 2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet therapy and dual or triple therapy were increased for either aneurysm coiling and percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic complications were significantly decreased (4.2% vs. 2.1%, p < 0.001), hemorrhagic complications (2.1% vs. 5.3%, p < 0.001), severe adverse events (1.5% vs. 2.1%, p < 0.001), and total perioperative complications (8.3% vs. 10.3%, p < 0.001) were significantly increased in JR-NET2. The rate of hemorrhagic complications was significantly higher in patients with triple or more perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p < 0.0001, postoperative: 5.7% vs. 12.7%, p < 0.0001). Perioperative antithrombotic therapy was performed more frequently and intensively in neuroendovascular therapy in Japan. While ischemic complications were decreased, hemorrhagic complications and severe adverse events were increased. These results suggest that intensive antithrombotic therapy has a potential risk of hemorrhagic complications for Japanese patients. PMID:24305029

  4. Direct Oral Anticoagulants: Monitoring Anticoagulant Effect.

    PubMed

    Konkle, Barbara A

    2016-10-01

    In some clinical settings laboratory measurement of direct oral anticoagulants effect is helpful in guiding medical care, such as life-threatening bleeding, need for emergency surgery, renal impairment, severe hepatic failure, extremes of body weight, or in patients with bleeding or thrombosis on therapy. This article reviews approaches to laboratory testing to assess the anticoagulant effect of these drugs. Because of the wide variation in levels measured in patients on therapy and minimal clinical data from dose adjustment, dose adjustment based on levels is not currently advised. In addition, these drugs interfere with many clot-based laboratory tests and caution is advised in interpreting these tests in patients on direct oral anticoagulants. PMID:27637303

  5. Use and Outcomes of Antiarrhythmic Therapy in Patients with Atrial Fibrillation Receiving Oral Anticoagulation: Results from the ROCKET AF Trial

    PubMed Central

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

    2014-01-01

    Background Antiarrhythmic drugs (AAD) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. Objective We aimed to study the use and outcomes of AAD therapy in anticoagulated AF patients. Methods Patients in the ROCKET AF trial (n=14,264) were grouped by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across groups, as well as across treatment assignment (rivaroxaban or warfarin). Results Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone, 537 [3.8%] with other AADs). Amiodarone-treated patients were less-often female (38% vs. 48%), had more persistent AF (64% vs. 40%), and more concomitant heart failure (71% vs. 41%) than patients receiving other AADs. Patients receiving no AAD more closely-resembled amiodarone-treated patients. Time in therapeutic range was significantly lower in warfarin-treated patients receiving amiodarone versus no AAD (50% vs. 58%, p<0.0001). Compared with no AAD, neither amiodarone (adjusted HR 0.98, 95% CI 0.74–1.31, p=0.9) nor other AADs (adjusted HR 0.66, 95% CI 0.37–1.17, p=0.15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Rivaroxaban treatment effects in patients not on an AAD were consistent with the overall trial (primary endpoint adjusted HR 0.82, 95% CI 0.68–0.98, pinteraction=0.06; safety endpoint adjusted HR 1.12, 95% CI 0.90–1.24, pinteraction=0.33). Conclusion Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The influence of amiodarone on outcomes in patients receiving rivaroxaban requires further study. PMID:24833235

  6. Effectiveness of self-managed oral anticoagulant therapy in patients with recurrent venous thromboembolism. A propensity-matched cohort study.

    PubMed

    Larsen, Torben Bjerregaard; Skjøth, Flemming; Grove, Erik Lerkevang; Nielsen, Peter Brønnum; Christensen, Thomas Decker

    2016-08-30

    Patient-self-management (PSM) of oral anticoagulant therapy (OAT) with vitamin K antagonists for venous thromboembolism (VTE) has demonstrated efficacy in randomised, controlled trials. The aim of this study was to evaluate the effectiveness of PSM of OAT in everyday clinical practice. Prospectively registered patient data were obtained from databases at two hospitals, and cross-linkage with national patient registries provided detailed information on comorbidities and events. Patients with VTE performing PSM affiliated to major PSM centres were included as cases (N=444). A control group of patients on conventional treatment was propensity score selected in a ratio of 1:5 (N=2220) within matched groups. The effectiveness and safety was estimated using recurrent VTE, major bleeding events and all-cause death as outcomes. We found a lower rate of recurrent VTE among PSM patients compared to the control group with a hazard ratio (HR) of 0.63; 95 % confidence interval (CI) 0.42-0.95, whereas no difference was seen with bleeding (HR: 0.95; 95 % CI 0.44-2.02). The risk of all-cause death was lower for PSM patients (HR: 0.41; 95 % CI 0.21-0.81). A net clinical benefit analysis sums the effect on recurrent VTE and bleeding up to a weighted rate difference of 0.86 (95 % CI 0.00-1.72) in favour of PSM. In conclusion, PSM of anticoagulant treatment was associated with a statistically significant lower rate of recurrent VTE and all-cause death compared to patients on conventionally managed anticoagulant treatment. All major thromboembolic outcomes were less frequent among self-managed patients, whereas bleedings were observed with similar frequency. PMID:27412804

  7. Anticoagulation: monitoring of patients receiving anticoagulation.

    PubMed

    Hawes, Emily M; Viera, Anthony J

    2014-07-01

    For patients with acute venous thromboembolism treated with warfarin, parenteral anticoagulation should be continued for a minimum of 5 days and until the international normalized ratio (INR) is 2 or greater for at least 24 hours. Early initiation of warfarin therapy is recommended. The goal therapeutic INR range for patients treated with warfarin is most commonly 2 to 3. During maintenance warfarin therapy, validated decision-support tools should be used to guide dosing. For patients with stable INRs, frequency of INR testing can be extended from every 4 weeks to up to 12 weeks. Self-testing and self-management can be safe options for patients receiving warfarin who are motivated and show competence. Patients starting anticoagulation therapy should receive education on treatment goals, adverse effects, and monitoring strategy. Physicians deciding whether to prescribe one of the new oral anticoagulants instead of warfarin should assess for possible drug interactions and for renal and hepatic impairment and should consider the financial cost to the patient. No routine coagulation assay monitoring is required for patients receiving apixaban, dabigatran, or rivaroxaban. Physicians who oversee oral anticoagulation therapy should do so in a systematic and coordinated fashion.

  8. Combination Therapy with Systemic Steroids, an Antiviral Agent, Anticoagulants, and Stellate Ganglion Block for Treatment of Sudden Sensorineural Hearing Loss

    PubMed Central

    Lee, Chi-Kyou; Lee, Jong Dae; Park, Moo Kyun; Lee, Byung Don

    2012-01-01

    Background and Objectives Sudden sensorineural hearing loss (SSNHL) is commonly defined as a loss of at least 30 dB in three contiguous frequencies occurring within 3 days. Systemic steroid administration has become the most widely accepted treatment option for SSNHL. Since viral infection and vascular compromise are considered specific causes of SSNHL, antiviral agents, anticoagulants, and stellate ganglion block have been used for its treatment, although the evidence of their effectiveness is weak. The present study evaluated the hearing recovery rate in the combination therapy group (systemic steroids, antiviral agent, anticoagulants, and stellate ganglion block) in comparison with patients treated with systemic steroids alone. Subjects and Methods A total of 85 patients diagnosed with SSNHL were treated with combination therapy (group A, 46 patients) or systemic steroids only (group B, 39 patients). Hearing improvement was defined as a hearing gain of more than slight improvement using Siegel's criteria. All patients were treated with a 10-day course of systemic steroids (10-mg dexamethasone for 5 days, followed by tapering for 5 days). Acyclovir, heparin, and stellate ganglion block were included in the group A treatment regimen. Results The overall rate of hearing improvement was 60.9% (28/46 patients) in group A, which was significantly higher than that (38.5%, 15/39 patients) in group B. The distribution of prognostic factors was not significantly different between the two groups with the exception of the degree of initial hearing loss, which was more severe in group A. Upon analysis according to prognostic factors, group A showed a better hearing improvement recovery rate than group B in patients with hearing loss >70 dB, age >41 years, dizziness, and early treatment (<1 week). Conclusions Thus SSNHL patients treated with combination therapy have a higher likelihood of hearing improvement than those treated with systemic steroids alone. PMID:24653874

  9. Review: anticoagulation for haemodialysis.

    PubMed

    Suranyi, Michael; Chow, Josephine S F

    2010-06-01

    The coagulation cascade is complex but well studied. Dialysis membranes and lines are inherently pro-coagulant and activate both the intrinsic and extrinsic pathways of coagulation, as well as platelets and other circulating cellular elements. To provide safe and effective dialysis, appropriate anticoagulant measures must be applied. Haemodialysis, including anticoagulation, is prescribed by dialysis doctors but delivered by dialysis nurses. The main agents used in clinical practice for anticoagulation during haemodialysis are unfractionated heparin (UF heparin) and low-molecular-weight heparin (LMWH). LMWH has a number of potential advantages, apart from cost. One of the most serious complications of the use of any form of heparin is heparin-induced thrombocytopaenia (HIT) Type II, which occurs more commonly with UF heparin than LMWH. HIT Type II risks severe morbidity and mortality and is challenging to treat successfully in both the acute and chronic phase. In HIT Type II anticoagulation must be delivered without heparin. A wide array of newer anticoagulants are becoming progressively available, each with unique advantages and disadvantages. In maintenance haemodialysis patients with an increased risk of bleeding, a 'no heparin' dialysis may be undertaken, or regional anticoagulation considered. Because this aspect of dialysis is so important to the safe and effective delivery of haemodialysis therapy, dialysis clinicians need to review and update their knowledge of dialysis anticoagulation on a regular basis. PMID:20609088

  10. Detecting nonvalvular atrial fibrillation and anticoagulant therapy in cardioembolic ischemic stroke.

    PubMed

    Min, Jiangyong; Farooq, Muhammad Umar

    2016-08-01

    Nonvalvular Atrial fibrillation (NVAF) is the most common cardiac arrhythmia associated with an increase in risk of stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home. The present review will focus on the current status of detecting NVAF and stroke prevention when there is AF. The CHA2DS2-VASc risk stratification scheme is discussed for the identification of patients who are at risk for thromboembolic stroke related to NVAF. Patient with a CHA2DS2-VASc score of 2 or greater are candidates for warfarin or a novel oral anticoagulant, irrespective of whether the strategy is for rate or rhythm control. Finally, guidelines and landmark clinical trials in NVAF patients with primary or secondary stroke prevention are discussed. PMID:27263867

  11. Discrepancies between Patients’ Preferences and Educational Programs on Oral Anticoagulant Therapy: A Survey in Community Pharmacies and Hospital Consultations

    PubMed Central

    Macquart de Terline, Diane; Hejblum, Gilles; Fernandez, Christine; Cohen, Ariel; Antignac, Marie

    2016-01-01

    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

  12. Supporting patients to self-monitor their oral anticoagulation therapy: recommendations based on a qualitative study of patients’ experiences

    PubMed Central

    Tompson, Alice; Heneghan, Carl; Fitzmaurice, David; Sutton, Stephen; Harrison, Sian; Ward, Alison

    2015-01-01

    Background Clinical trials suggest that oral anticoagulation therapy (OAT) self-monitoring is safe and effective, however little is known about the patient experience of this process. There is a lack of understanding about how best to train and support patients embarking on OAT self-monitoring. Aim To collect in-depth information about patients’ experiences of OAT self-monitoring outside of clinical trial conditions and to produce a set of recommendations on how best to support such patients. Design and setting Semi-structured qualitative interviews with patients who self-monitor and live in England. Method In total, 26 of the 267 (9.7%) who participated in the Cohort study of Anticoagulation Self-Monitoring (CASM) and were still self-monitoring after 12 months’ follow-up were interviewed. Topics discussed included experiences of OAT self-monitoring, healthcare support, training, and decision making. Framework analysis was used. Results Following initial problems using the monitoring device, interviewees described a mostly positive experience. Although less effort was expended attending monitoring appointments with health professionals, effort was required to conduct self-monitoring tests and to interpret and act on the results. Desire to self-manage was variable, especially when dosing advice systems worked promptly and reliably. Interviewees overcame patchy healthcare system knowledge and support of self-monitoring by educating themselves. Family and friends provided support with learning to use the monitor and managing OAT dosage adjustments. Conclusion Better, more-consistent training and health-service support would have alleviated a number of problems encountered by these patients who were self-monitoring. This training and support will become even more important if self-monitoring becomes more accessible to the general population of people on OAT. PMID:26077266

  13. Maternal Malaria Induces a Procoagulant and Antifibrinolytic State That Is Embryotoxic but Responsive to Anticoagulant Therapy

    PubMed Central

    Avery, John W.; Smith, Geoffrey M.; Owino, Simon O.; Sarr, Demba; Nagy, Tamas; Mwalimu, Stephen; Matthias, James; Kelly, Lauren F.; Poovassery, Jayakumar S.; Middii, Joab D.; Abramowsky, Carlos; Moore, Julie M.

    2012-01-01

    Low birth weight and fetal loss are commonly attributed to malaria in endemic areas, but the cellular and molecular mechanisms that underlie these poor birth outcomes are incompletely understood. Increasing evidence suggests that dysregulated hemostasis is important in malaria pathogenesis, but its role in placental malaria (PM), characterized by intervillous sequestration of Plasmodium falciparum, proinflammatory responses, and excessive fibrin deposition is not known. To address this question, markers of coagulation and fibrinolysis were assessed in placentae from malaria-exposed primigravid women. PM was associated with significantly elevated placental monocyte and proinflammatory marker levels, enhanced perivillous fibrin deposition, and increased markers of activated coagulation and suppressed fibrinolysis in placental plasma. Submicroscopic PM was not proinflammatory but tended to be procoagulant and antifibrinolytic. Birth weight trended downward in association with placental parasitemia and high fibrin score. To directly assess the importance of coagulation in malaria-induced compromise of pregnancy, Plasmodium chabaudi AS-infected pregnant C57BL/6 mice were treated with the anticoagulant, low molecular weight heparin. Treatment rescued pregnancy at midgestation, with substantially decreased rates of active abortion and reduced placental and embryonic hemorrhage and necrosis relative to untreated animals. Together, the results suggest that dysregulated hemostasis may represent a novel therapeutic target in malaria-compromised pregnancies. PMID:22347435

  14. [GOOD PLANNING PRACTICE IN PRECLINICAL AND CLINICAL STUDIES OF UNFRACTIONATED AND FRACTIONATED HEPARINS IN RUSSIA AS THE BASIS OF SAFE AND EFFECTIVE ANTICOAGULATION THERAPY].

    PubMed

    Gavrishina, E V; Dobrovolskii, A V; Niyazov, R R; Romodanovskii, D P; Vasil'ev, A N

    2015-01-01

    General principles of appropriate strategies for preclinical and clinical development of unfractionated and low-molecular-weight heparins and demonstration of their biosimilarity to corresponding reference medicinal products are provided. Demonstration of the biosimilarity of heparin-containing medicinal products constitutes the basis for their efficacy and safety during anticoagulation therapy. The main quality, safety, and efficacy characteristics of heparin products are described and the extent of non-clinical and clinical investigations necessary prior to drug marketing authorization are considered. PMID:27017700

  15. New Prospective for the Management of Low-Risk Pulmonary Embolism: Prognostic Assessment, Early Discharge, and Single-Drug Therapy with New Oral Anticoagulants

    PubMed Central

    2012-01-01

    Patients with pulmonary embolism (PE) can be stratified into two different prognostic categories, based on the presence or absence of shock or sustained arterial hypotension. Some patients with normotensive PE have a low risk of early mortality, defined as <1% at 30 days or during hospital stay. In this paper, we will discuss the new prospective for the optimal management of low-risk PE: prognostic assessment, early discharge, and single-drug therapy with new oral anticoagulants. Several parameters have been proposed and investigated to identify low-risk PE: clinical prediction rules, imaging tests, and laboratory markers of right ventricular dysfunction or injury. Moreover, outpatient management has been suggested for low-risk PE: it may lead to a decrease in unnecessary hospitalizations, acquired infections, death, and costs and to an improvement in health-related quality of life. Finally, the main characteristics of new oral anticoagulant drugs and the most recent published data on phase III trials on PE suggest that the single-drug therapy is a possible suitable option. Oral administration, predictable anticoagulant responses, and few drug-drug interactions of direct thrombin and factor Xa inhibitors may further simplify PE home therapy avoiding administration of low-molecular-weight heparin. PMID:24278706

  16. Melagatran and ximelagatran: new drug. No real simplification of anticoagulant therapy.

    PubMed

    2005-08-01

    increased risk of adverse effects due to overdosing. There is no available antidote if overdose occurs. (10) Erythromycin increases melagatran bioavailability, thereby increasing the bleeding risk. Melagatran and ximelagatran must not be combined with other anticoagulants, thrombolytic agents or antiplatelet drugs because of a increased bleeding risk. (11) In practice, low-molecular-weight heparin remains the reference prophylactic treatment for venous thromboembolism after hip or knee replacement surgery.

  17. Anticoagulant therapy during pregnancy for maternal and fetal acquired and inherited thrombophilia.

    PubMed

    Giannubilo, S R; Tranquilli, A L

    2012-01-01

    Thromboembolism is an infrequent, yet serious cause of both maternal and fetal morbidity and death during pregnancy and the puerperium. Antithrombotic treatment and prophylaxis both before and during pregnancy are based on unfractionated heparin (UH), low-molecularweight heparin (LMWH), Warfarin and Aspirin. The prevalence and severity of thromboembolism during pregnancy and puerperium warrant special consideration of management and therapy. Such therapy includes the treatment of acute thrombotic events and prophylaxis for those at increased risk of thrombotic events. This paper assesses the safety and efficacy of antithrombotic therapy during pregnancy and the peripartum period. Its cardiovascular and obstetric indications, the evidence of association between thrombophilias and adverse pregnancy outcome, regimens and maternal and fetal side-effects are also discussed. PMID:22876895

  18. Anticoagulant rodenticides.

    PubMed

    Watt, Barbara E; Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister

    2005-01-01

    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

  19. Drug persistence with rivaroxaban therapy in atrial fibrillation patients—results from the Dresden non-interventional oral anticoagulation registry

    PubMed Central

    Beyer-Westendorf, Jan; Förster, Kati; Ebertz, Franziska; Gelbricht, Vera; Schreier, Thomas; Göbelt, Maria; Michalski, Franziska; Endig, Heike; Sahin, Kurtulus; Tittl, Luise; Weiss, Norbert

    2015-01-01

    Aims Worldwide, rivaroxaban is increasingly used for stroke prevention in atrial fibrillation (SPAF) but little is known about the rates of or reasons for rivaroxaban discontinuations in daily care. Using data from a prospective, non-interventional oral anticoagulation (NOAC) registry, we analysed rivaroxaban treatment persistence. Methods and results Persistence with rivaroxaban in SPAF was assessed in an ongoing, prospective, non-interventional registry of >2600 NOAC patients from daily care using the Kaplan–Meier time-to-first-event analysis. Reasons for and management of rivaroxaban discontinuation were assessed. Potential baseline risk factors for treatment discontinuation were evaluated using Cox regression analysis. Between October 2011 and April 2014, 1204 rivaroxaban SPAF patients were enrolled [39.3% switched from vitamin K antagonists (VKAs) and 60.7% newly treated patients]. Of these, 223 patients (18.5%) stopped rivaroxaban during follow-up (median 544 days), which translates into a discontinuation rate of 13.6 (95% CI 11.8–15.4) per 100 patient-years. Most common reasons for treatment discontinuations were bleeding complications (30% of all discontinuations), followed by other side-effects (24.2%) and diagnosis of stable sinus rhythm (9.9%). A history of chronic heart failure (HR 1.43; 95% CI 1.09–1.87; P = 0.009) or diabetes (HR 1.39; 95% CI 1.06–1.82; P = 0.018) were the only statistically significant baseline risk factors for rivaroxaban discontinuation. After discontinuation of rivaroxaban, patients received antiplatelet therapy (31.8%), VKA (24.2%), another NOAC (18.4%), heparin (9.9%), or nothing (15.7%). Conclusion Our data indicate that overall persistence with rivaroxaban therapy is high, with a discontinuation rate of ∼15% in the first year of treatment and few additional discontinuations thereafter. PMID:25694537

  20. [Should we add antiplatelet therapy to oral anticoagulation in patients with atrial fibrillation and vascular disease? Review of available evidence].

    PubMed

    Andreu, José Manuel; Roldán, Vanessa; García-Navarro, Miguel; Ruipérez, Juan Antonio; Valdés, Mariano; Marín, Francisco

    2012-01-01

    Current recommendation is to add antiplatelet drug to oral anticoagulation in patients with atrial fibrillation (AF) and vascular disease. However, it is debatable to join both antithrombotic drugs in stable vascular disease.

  1. Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy

    PubMed Central

    2009-01-01

    Executive Summary Subject of the Evidence-Based Analysis The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care (POC) international normalized ratio (INR) monitoring devices for patients on long-term oral anticoagulation therapy (OAT). Clinical Need: Target Population and Condition Long-term OAT is typically required by patients with mechanical heart valves, chronic atrial fibrillation, venous thromboembolism, myocardial infarction, stroke, and/or peripheral arterial occlusion. It is estimated that approximately 1% of the population receives anticoagulation treatment and, by applying this value to Ontario, there are an estimated 132,000 patients on OAT in the province, a figure that is expected to increase with the aging population. Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range. This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses. Optimal INR scores depend on the underlying indication for treatment and patient level characteristics, but for most patients the therapeutic range is an INR score of between 2.0 and 3.0. The current standard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics (ACCs). Patients also regularly visit a hospital or community-based facility to provide a venous blood samples (venipuncture) that are then sent to a laboratory for INR analysis. Experts, however, have commented that there may be under-utilization of OAT due to patient factors, physician factors, or regional practice variations and that sub-optimal patient management may also occur. There is currently no population-based Ontario data to permit the assessment of patient care, but recent systematic reviews have estimated that less that 50% of patients receive OAT on a

  2. New anticoagulants.

    PubMed

    Weitz, J I; Bates, S M

    2005-08-01

    The limitations of heparin and warfarin have prompted the development of new anticoagulant drugs for prevention and treatment of venous and arterial thromboembolism. Novel parenteral agents include synthetic analogs of the pentasaccharide sequence of heparin that mediates its interaction with antithrombin. Fondaparinux, the first synthetic pentasaccharide, is licensed for prevention of venous thromboembolism (VTE) after major orthopedic surgery and for initial treatment of patients with VTE. Idraparinux, a long-acting pentasaccharide that is administered subcutaneously once-weekly, is being compared with warfarin for treatment of VTE and for prevention of cardioembolic events in patients with atrial fibrillation. New oral anticoagulants include direct inhibitors of thrombin, factor Xa and factor IXa. Designed to provide more streamlined anticoagulation than warfarin, these agents can be given without routine coagulation monitoring. Ximelagatran, the first oral direct thrombin inhibitor, is as effective and safe as warfarin for prevention of cardioembolic events in patients with atrial fibrillation. However, ximelagatran produces a three-fold elevation in alanine transaminase levels in 7.9% of patients treated for more than a month, the long-term significance of which is uncertain. Whether other direct thrombin inhibitors or inhibitors of factors Xa or IXa also have this problem is under investigation. After a brief review of coagulation pathways, this paper focuses on new anticoagulants in advanced stages of clinical testing. PMID:16102051

  3. Anticoagulation in atrial fibrillation

    PubMed Central

    Piccini, Jonathan P

    2014-01-01

    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

  4. Non-Vitamin K Antagonist Oral Anticoagulants and Antiplatelet Therapy for Stroke Prevention in Patients With Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Kumar, Shashi; Danik, Stephan B; Altman, Robert K; Barrett, Conor D; Lip, Gregory Y H; Chatterjee, Saurav; Roubin, Gary S; Natale, Andrea; Danik, Jacqueline S

    2016-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are frequently used to prevent stroke in patients with atrial fibrillation. These patients are often also on aspirin or other antiplatelet agents. It is possible that treatment with both NOACs and aspirin or other antiplatelet drug may be effective in decreasing stroke, but data are sparse regarding the efficacy and safety of using both agents for stroke prevention. To address these issues, data were pooled from the 4 recent randomized, controlled trials of NOACs: apixaban, rivaroxaban, dabigatran, and edoxaban, which included 42,411 patients; 14,148 (33.4%) were also on aspirin or other antiplatelet drug. The number of thromboembolic events among participants on NOAC and aspirin/antiplatelet was compared with the number of events in patients on NOAC alone. Bleeding rates were also compared between those on NOAC + aspirin/antiplatelet and on NOAC alone. These results were compared with thromboembolic and bleeding events in the warfarin + aspirin/antiplatelet versus warfarin alone. No greater risk for thromboembolism was seen in patients on NOACs compared with patients on both NOACs and aspirin/antiplatelet drug. In this nonrandomized comparison, there was initially a signal toward higher thromboembolic rates among NOAC users also on aspirin/antiplatelet drugs (relative risk, 1.16; 95% confidence intervals, 1.05, 1.29) when compared with NOAC alone. This likely reflected the higher CHADS2 scores of those on aspirin/antiplatelet drugs. When the analysis was limited to studies that included aspirin rather than other antiplatelet drugs, no difference was seen for thromboembolic rates comparing dual therapy to NOAC alone (relative risk, 1.02; 95% confidence intervals, 0.90, 1.15). Higher rates of bleeding were seen with aspirin/antiplatelet drug in conjunction with NOAC. In this meta-analysis and nonrandomized comparison of aspirin/antiplatelet users and nonusers also on anticoagulation, there was no additional

  5. Point of care monitoring of oral anticoagulant therapy in children: comparison of CoaguChek Plus and Thrombotest methods with venous international normalised ratio.

    PubMed

    Ignjatovic, Vera; Barnes, Chris; Newall, Fiona; Hamilton, Simone; Burgess, Janet; Monagle, Paul

    2004-10-01

    This paper reports the outcome of a research protocol aimed at optimising warfarin monitoring in a tertiary pediatric centre. The Thrombotest INR was the standard monitoring test employed to manage oral anticoagulant therapy in children at the Royal Children's Hospital (RCH), Melbourne. This study compares the results of this standard method to the novel CoaguChek INR monitor and the "gold standard" technique of venous INR sampling. The objectives were to determine 1) if point-of-care techniques of measuring the INR (Thrombotest and CoaguChek) are accurate and reliable compared to INR results obtained from venous sampling, processed in an accredited laboratory, and 2) if INR results generated by POC devices can be safely used to manage oral anticoagulant therapy in children. 18 children (10 females and 8 males) participated in the study. Ages ranged from 9 months to 21 years (Mean 11.9 years; SD 5.03 years). The agreement between CoaguChek and venous INR measurements (r = 0.885) was shown to be higher compared to Thrombotest and venous INR (r = 0.700). Compared to the venous INR, values obtained with Coaguchek and Thrombotest crossed into or out of the therapeutic range in 25% and 36% of cases respectively. In 88% of the CoaguChek cases and 57% Thrombotest cases, the difference from the venous result was less than 0.5. The CoaguChek method of INR monitoring is a more accurate and reliable method compared to Thrombotest, in the pediatric population tested, and can be safely used to manage oral anticoagulant therapy in children.

  6. Long-term anticoagulation. Indications and management.

    PubMed Central

    Stults, B M; Dere, W H; Caine, T H

    1989-01-01

    Each year half a million persons in the United States receive long-term anticoagulant therapy to prevent venous and arterial thromboembolism. Unfortunately, the relative benefits and risks of anticoagulant therapy have not been adequately quantified for many thromboembolic disorders, and the decisions as to whether, for how long, and how intensely to administer anticoagulation are often complex and controversial. Several expert panels have published recommendations for anticoagulant therapy for different thromboembolic disorders; the primary area of disagreement among these panels concerns the optimal intensity of anticoagulation. Recent research and analytic reviews have helped to clarify both the risk factors for and the appropriate diagnostic evaluation of anticoagulant-induced hemorrhage. Clinicians must be aware of the nonhemorrhagic complications of anticoagulant therapy, particularly during pregnancy. The administration of anticoagulants is difficult both in relation to dosing and long-term monitoring. Knowledge of the pharmacology of the anticoagulants, an organized approach to ongoing monitoring, and thorough patient education may facilitate the safe and effective use of these drugs. PMID:2686173

  7. Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

    SciTech Connect

    Cakir, Volkan; Gulcu, Aytac; Akay, Emrah; Capar, Ahmet E.; Gencpinar, Tugra; Kucuk, Banu; Karabay, Ozalp; Goktay, A. Yigit

    2014-08-15

    PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

  8. Short-Term Anticoagulant Therapy and Thrombus Location Are Independent Risk Factors for Delayed Recanalization of Deep Vein Thrombosis

    PubMed Central

    Zhang, Chuanlin; Fu, Qining; Zhao, Yu; Mu, Shaoyu; Liu, Liping

    2016-01-01

    Background Prompt recanalization of the vein containing the thrombus is an important goal during the initial treatment of DVT, and risk factors for delayed recanalization in patients with deep vein thrombosis (DVT) in the lower extremities need to be determined. Material/Methods A total of 174 patients with DVT in lower extremities were recruited from June 2014 to March 2015 at our hospital. Duplex ultrasound scanning was conducted for all patients at 1 and 6 months after baseline evaluation. We divided the patients into recanalization and non-recanalization groups and analyzed risk factors for delayed recanalization. Results The univariate analysis revealed that an oral anticoagulant time of less than 3 months and venous thrombus location were risk factors for delayed recanalization (P<0.01). However, age, gender, hypertension, diabetes, pulmonary embolism, incidence factors, the use of catheter-directed thrombolytic (CDT) drugs, and inferior vena cava filter (IVCF) implantation had no influence on the incidence of delayed recanalization in patients with DVT (P>0.05). The multivariate analysis showed that patients with an anticoagulant time of less than 3 months had a lower incidence of recanalization than those with an anticoagulant time of more than 3 months (OR=2.358, P<0.05). The risk of delayed recanalization in patients with proximal DVT was 7 times higher than that in patients with distal DVT. Conclusions Duration of anticoagulant treatment of less than 3 months and venous thrombus location are independent risk factors for delayed recanalization of DVT in the lower extremities. PMID:26790571

  9. Attitudes and Preferences on the Use of Mobile Health Technology and Health Games for Self-Management: Interviews With Older Adults on Anticoagulation Therapy

    PubMed Central

    Nguyen, Annie Lu; Berg, Jill; Amin, Alpesh; Bachman, Mark; Guo, Yuqing; Evangelista, Lorraine

    2014-01-01

    Background Older adults are at substantial risk for cardiovascular disorders that may require anticoagulation therapy. Those on warfarin therapy report dissatisfaction and reduced quality of life (QOL) resulting from the treatment. Advances in the area of mobile health (mHealth) technology have resulted in the design and development of new patient-centric models for the provision of personalized health care services to improve care delivery. However, there is a paucity of research examining the effectiveness of mHealth tools on knowledge, attitudes, and patient satisfaction with treatment, as well as self-management, adherence to therapy, and QOL in older adults with chronic illness conditions requiring long-term warfarin therapy. Objective The objective of the study was to explore the attitudes and preferences of older adults on warfarin therapy regarding the use of mHealth technology and health games to gain skills for self-management. Methods We conducted group and individual interviews with patients (60 years or older) on warfarin therapy at two anticoagulation clinics affiliated with an academic medical center. We held 4 group and 2 individual interviews, resulting in 11 patient participants and 2 family caregiver participants. We used structured questions on three topic areas including medication self-management strategies, mHealth technology use, and health games for exercise. We demonstrated some commercial health apps related to medication management, vitamin K content of food, and a videogame for balance exercise. Discussions were audiotaped and transcribed verbatim. Common themes were drawn using content analysis. Results The participants reported awareness of the importance of staying on schedule with warfarin therapy. They also acknowledged that negative experiences of friends or family members who were taking warfarin influenced their desire to keep on schedule with warfarin therapy. In addition, the participants expressed that the use of m

  10. Prognostic usefulness of left ventricular hypertrophy by electrocardiography in patients with atrial fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study).

    PubMed

    Verdecchia, Paolo; Reboldi, Gianpaolo; Di Pasquale, Giuseppe; Mazzotta, Giovanni; Ambrosio, Giuseppe; Yang, Sean; Pogue, Janice; Wallentin, Lars; Ezekowitz, Michael D; Connolly, Stuart J; Yusuf, Salim

    2014-02-15

    It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF.

  11. Considerations for Systemic Anticoagulation in ESRD.

    PubMed

    Dager, William E; Tsu, Laura V; Pon, Tiffany K

    2015-01-01

    In the setting of end-stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end-stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.

  12. [Direct oral anticoagulants in cardiology].

    PubMed

    Kiss, Róbert Gábor

    2016-09-01

    Antithrombotic drug therapy is a main cornerstone - sometimes a fairly uneven cornerstone - of today's clinical practice. Patients treated with antithrombotic drugs appear sometimes unawaited at those of our colleagues, who are not necessarily experts of this narrow field. Furthermore, new and newer molecules of antiplatelet and anticoagulant medicines have come into practice, frequently in combination. This dramatic development has been important to patients; pharmacological - and recently nonpharmacological - antithrombotic treatment has paved the way to improve current modalities in cardiology. Combining elements of the "old four" (heparin, coumadin, aspirin, clopidogrel) have been the basis of any improvement for a long time. Nowadays, there has been an involvement of new drugs, direct oral anticoagulants into practice. It is time now to catch up in using new anticoagulants, regardless of our current speciality in medicine. Orv. Hetil., 2016, 157(38), 1507-1510. PMID:27640616

  13. Practical management of anticoagulation in patients with atrial fibrillation.

    PubMed

    Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

    2015-04-01

    Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. PMID:25835447

  14. Practical management of anticoagulation in patients with atrial fibrillation.

    PubMed

    Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

    2015-04-01

    Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation.

  15. Validation of the international normalized ratio (INR) in a new point-of-care system designed for home monitoring of oral anticoagulation therapy.

    PubMed

    Plesch, W; van den Besselaar, A M H P

    2009-02-01

    The new CoaguChek XS system is designed for use in patient self testing with a measuring range from 0.8 INR up to 8.0 INR, which has been calibrated against the mean INR of rTF/95 and ERM-AD149. This study was performed to confirm the correct INR results received from two routinely manufactured lots of test strips when compared with the international reference preparations (IRP) rTF/95 and ERM-AD149. At one study site capillary and noncitrated venous whole blood samples from 20 normal donors and 62 anticoagulated patients were applied to two test strip lots of the new system in duplicate. Additionally blood was collected in citrate tubes, processed to plasma, and PT results were obtained using rTF/95 and ERM-AD149 by the manual tilt tube method. Method comparisons of the INR results of the CoaguChek XS system vs. the mean INR of the IRP demonstrated a mean relative bias of -0.02% to -0.4%, mean absolute relative deviations of 6.4-9.6%, and accuracy observing >95% of CoaguChek XS INR within limits of +/-14% to +/-21.5% to the mean INR of the IRP. The results of the study confirm the successful calibration of two lots of the new CoaguChek XS system, demonstrate the validity of the calibration concept and prove the accuracy of the new system in comparison with the IRP. Clinical decisions in oral anticoagulation therapy may be reliably made upon the INR results of the new system.

  16. Engaging with quality improvement in anticoagulation management.

    PubMed

    Barnes, Geoffrey D; Kline-Rogers, Eva

    2015-04-01

    Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process.

  17. Engaging with quality improvement in anticoagulation management

    PubMed Central

    Barnes, Geoffrey D.; Kline-Rogers, Eva

    2016-01-01

    Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process. PMID:25772116

  18. Anticoagulant modulation of inflammation in severe sepsis.

    PubMed

    Allen, Karen S; Sawheny, Eva; Kinasewitz, Gary T

    2015-05-01

    Inflammation and coagulation are so tightly linked that the cytokine storm which accompanies the development of sepsis initiates thrombin activation and the development of an intravascular coagulopathy. This review examines the interaction between the inflammatory and coagulation cascades, as well as the role of endogenous anticoagulants in regulating this interaction and dampening the activity of both pathways. Clinical trials attempting to improve outcomes in patients with severe sepsis by inhibiting thrombin generation with heparin and or endogenous anticoagulants are reviewed. In general, these trials have failed to demonstrate that anticoagulant therapy is associated with improvement in mortality or morbidity. While it is possible that selective patients who are severely ill with a high expected mortality may be shown to benefit from such therapy, at the present time none of these anticoagulants are neither approved nor can they be recommended for the treatment of sepsis. PMID:25938026

  19. A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy

    PubMed Central

    Koyama, Yasushi; Suzuki, Yasuo

    2016-01-01

    A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy. PMID:27672472

  20. A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy.

    PubMed

    Chinen, Naofumi; Koyama, Yasushi; Sato, Shinji; Suzuki, Yasuo

    2016-01-01

    A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy. PMID:27672472

  1. A Case of Acute Budd-Chiari Syndrome Complicating Primary Antiphospholipid Syndrome Presenting as Acute Abdomen and Responding to Tight Anticoagulant Therapy

    PubMed Central

    Koyama, Yasushi; Suzuki, Yasuo

    2016-01-01

    A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. Optical profiling of anticoagulation status (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

    2016-02-01

    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.

  4. Anticoagulation in the Elderly

    PubMed Central

    Robert-Ebadi, Helia; Righini, Marc

    2010-01-01

    Management of anticoagulation in elderly patients represents a particularly challenging issue. Indeed, this patient population is at high thromboembolic risk, but also at high hemorrhagic risk. Assessment of the benefit-risk balance of anticoagulation is the key point when decisions are made about introducing and/or continuing such treatments in the individual elderly patient. In order to maximise the safety of anticoagulation in the elderly, some specific considerations need to be taken into account, including renal insufficiency, modified pharmacodynamics of anticoagulants, especially vitamin K antagonists, and the presence of multiple comorbidities and concomitant medications. New anticoagulants could greatly simplify and possibly increase the safety of anticoagulation in the elderly in the near future.

  5. [Extended options of anticoagulant treatment in thromboembolism].

    PubMed

    Karetová, Debora; Bultas, Jan

    2014-11-01

    Thromboembolic disease (TD) is a relatively common disease with acute risk of death and potential long-term consequences in term of postthrombotic syndrome or chronic pulmonary hypertension. Anticoagulant therapy is the basic therapeutic procedure; thrombolytic therapy and the introduction cava filter are appropriately indicated for individual cases. In past few years, new direct oral anticoagulant drugs (NOAC) have occurred - Xa factor or thrombin inhibitors which have demonstrated the same efficacy and even higher safety in comparison to conventional treatment. In mid 2014, 3 drugs of this group are registered in Czech Republic - rivaroxaban (Xarelto®), dabigatran (Pradaxa®) and apixaban (Eliquis®). These drugs have comparable efficacy and safety but they differ in schedule of dose administration. Rivaroxaban and apixaban can be administered immediately after diagnosis of venous thrombosis or hemodynamically stable pulmonary embolism. LMWH application has to precede few days the administration of dabigatran. Limitation of new drugs is their price. Unavailability of antidotes is temporary because current researches continue to find one for dabigatran and another for both of xabans. Duration of anticoagulant treatment after acute phase depends on the presence of thrombosis risk factors and the individual bleeding risk. Minimal duration of anticoagulant therapy is 3 months, commonly 6-12 months and in high risk patients it is "long term" treatment. Good results of new anticoagulant drugs in trials in term of thromboembolism recurrence prevention may change established habits in TD patients with long term treatment. PMID:25600045

  6. Newer Oral Anticoagulants: Stroke Prevention and Pitfalls

    PubMed Central

    Patel, Anand; Goddeau Jr, Richard P.; Henninger, Nils

    2016-01-01

    Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy. PMID:27347226

  7. Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

    SciTech Connect

    Rosenbaum, R.C.; Johnston, G.S.; Whitley, N.O.

    1986-02-01

    The exact location of hemorrhage complicating anticoagulant therapy is sometimes difficult to establish. We present a case in which imaging with 99mTc-labeled red cells had a significant role in the diagnosis of soft-tissue bleeding in a paraplegic patient receiving long-term anticoagulation.

  8. New Oral Anticoagulants for Atrial Fibrillation

    PubMed Central

    Shafeeq, Hira; Tran, Tran H.

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia in the U.S. Anticoagulation is recommended for stroke prevention in AF patients with intermediate-to-high stroke risk (i.e., patients with a CHADS2 score of 1 or greater). Warfarin was previously the only option for oral anticoagulation in these patients, but three new oral anticoagulants have become available as alternatives for warfarin in patients with nonvalvular AF. The advantages of the newer agents include a rapid onset, predictable pharmacokinetics, and no need for routine anticoagulation monitoring. Dabigatran (Pradaxa) and apixaban (Eliquis) have demonstrated improved efficacy compared with warfarin. Rivaroxaban (Xarelto) was non-inferior to warfarin for stroke prevention in AF. Apixaban demonstrated a reduced incidence of major bleeding compared with warfarin and a reduction in all-cause mortality. Limitations to the use of the new oral anticoagulants include the lack of a reversal agent; an inability to use the therapies in specific patient populations (such as those with severe renal or hepatic impairment); limited experience with drug–drug and drug–disease interactions; and a lack of available coagulation tests to quantify their effects. Although the newer agents have higher acquisition costs, the benefits of cost savings may be derived from the potential for decreasing the incidence of hemorrhagic stroke and intracranial bleeding and reducing the need for anticoagulation monitoring. Benefits and risks should be carefully weighed before these agents are prescribed for patients presenting with new-onset AF. PMID:24672216

  9. Perioperative management of patients receiving new oral anticoagulants: an international survey.

    PubMed

    Faraoni, David; Samama, Charles Marc; Ranucci, Marco; Dietrich, Wulf; Levy, Jerrold H

    2014-09-01

    New oral anticoagulants (NOACs) are increasingly replacing standard anticoagulants. These new drugs have been recently introduced in clinical practice, and specific knowledge regarding preoperative interruption, anticoagulation assessment, and reversal therapies is needed. In this article, 3 main areas related to perioperative NOACs management are discussed: (1) physicians' knowledge, (2) current practices, and (3) perspectives to improve management of patients treated with NOACs.

  10. Is anticoagulation required in plasmapheresis? A University Hospital Experience in Bogota, Colombia.

    PubMed

    Córdoba, Juan Pablo; Larrarte, Carolina; Ruiz, Alvaro

    2013-06-01

    Anticoagulation has been considered essential during plasmapheresis. International publications and guidelines state that anticoagulation should be administered during therapy to avoid circuit clotting and impaired effectiveness. However, anticoagulation has also been associated with bleeding, fluid and electrolyte imbalances and hematological alterations. No published studies have looked at the risk to benefit ratio of the common practice of circuit anticoagulation. We describe the experience with 367 plasmapheresis sessions, in the Hospital Universitario San Ignacio, a tertiary care center in Bogota, Colombia, where no anticoagulation is used in any case. Patient characteristics and therapy complications are described. Coagulation of circuit was never reported.

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

    PubMed Central

    Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria

    2016-01-01

    Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. Methods 133 OAT patients were recruited and assessed for warfarin/3’-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups Results In the whole OAT group both warfarin and 3’-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3’-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3’-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p<0.0001). Interestingly, 3’-hydroxywarfarin reached a strong correlation at c4 respect to warfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3’-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and

  12. Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals.

    PubMed

    Perram, Jacinta; Joseph, Joanne; Holloway, Cameron

    2015-01-01

    Compatibility of novel oral anticoagulants in patients with HIV taking combined antiretroviral therapy has not been established, with no published reports of successful concurrent use. We present a case where chronic anticoagulation was indicated in a patient with treated HIV and non-valvular atrial fibrillation who refused warfarin therapy. The patient tolerated the combination, with dabigatran blood levels within the expected range at a standard dosing regimen, without evidence of bleeding or other adverse outcomes. While further research is needed to establish the role of novel oral anticoagulants in patients taking antiretrovirals, this case suggests that dabigatran may be a viable option for selected patients.

  13. New oral anticoagulants: are coagulation units still required?

    PubMed Central

    2014-01-01

    Chronic antithrombotic therapy involves the use of anticoagulants, antiplatelets given either as monotherapy or in combination for the prevention of thrombotic complications. The most feared and sometimes fatal complication with this therapy is bleeding. It should be considered a “golden rule” that a drug or combination of drugs that maximizes efficiency (decreased thromboembolic risk) will probably be less safe (increased risk of bleeding), and this holds true either for single therapy or during combined therapy. The chances of bleeding indicated by risk tables can be useful but show only a snapshot, and the biological, social, environmental, and drug changes and therapeutic adherence also determine changes in the risk of thrombosis and bleeding. Bleeding is an eventuality that occurs in places of “locus minoris resistentiae,” and the results of careful phase 3 studies thus cannot be completely predictive of outcomes when a medication is introduced on the pharmaceutical market. With the use of warfarin, the International Normalized Ratio (INR) that has been established to indicate adequately balanced therapy is between 2.0 and 3.0. With the new oral anticoagulants, the pharmaceutical companies emphasize that it is not necessary to monitor anticoagulant effects. In studies with different doses of new oral anticoagulants, however, incidence of clinically significant bleeding complications have been directly related to the doses. Therefore, therapeutic excesses can condition bleeding risk and therapeutic limitation can increase thrombotic risk, especially when short-acting drugs such as the new oral anticoagulants are used. Hence, it is imperative to establish an appropriate method for monitoring new oral anticoagulants, setting levels of safety and effectiveness through periodic dosage and monitoring of their anticoagulant effects. Therefore, we still recommend the use of anticoagulation units for monitoring during treatment with the new oral anticoagulants

  14. Peri-procedural management of patients taking oral anticoagulants.

    PubMed

    Daniels, Paul R

    2015-07-14

    The use of oral anticoagulants is becoming increasingly common. For many years warfarin was the main oral anticoagulant available, but therapeutic options have expanded with the introduction of oral direct thrombin (dabigatran) and factor Xa inhibitors (apixaban, rivaroxaban, and edoxaban). Management of patients taking any oral anticoagulant in the peri-procedural period poses a challenge to medical and surgical providers because of the competing risks of thrombosis and hemorrhage. Bridging therapy has been used to minimize time without anticoagulation when warfarin is interrupted for invasive procedures, but validated strategies based on high quality data are lacking. Existing data suggest that the use of bridging therapy may increase the risk of bleeding for some patients without reducing the risk of thrombosis. Clinical trials are currently under way to answer these questions. Because the half lives and time to anticoagulant activity of newer oral anticoagulants are shorter than for warfarin, bridging therapy is not thought to be necessary with these agents. Peri-procedural management of patients taking these agents is complicated by the lack of demonstrated reversal agents in emergency situations, although specific antidotes are being developed and tested. Existing guidelines for peri-procedural management of patients on oral anticoagulants highlight the importance of individualized patient decision making and suggest strategies to minimize complications. From a patient's perspective, given the uncertainties surrounding optimal management, explicit discussions regarding risks and benefits of treatment options and demonstration of effective communication among medical and surgical providers are essential.

  15. New anticoagulants for the treatment of venous thromboembolism

    PubMed Central

    Fernandes, Caio Julio Cesar dos Santos; Júnior, José Leonidas Alves; Gavilanes, Francisca; Prada, Luis Felipe; Morinaga, Luciana Kato; Souza, Rogerio

    2016-01-01

    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. PMID:27167437

  16. Anticoagulation-related nephropathy.

    PubMed

    Wheeler, D S; Giugliano, R P; Rangaswami, J

    2016-03-01

    Anticoagulation-related nephropathy (ARN) is a significant but underdiagnosed complication of anticoagulation that is associated with increased renal morbidity and all-cause mortality. Originally described in patients receiving supratherapeutic doses of warfarin who had a distinct pattern of glomerular hemorrhage on kidney biopsy, ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. The underlying molecular mechanism is thought to be warfarin-induced thrombin depletion; however, newer studies have hinted at an alternative mechanism involving reductions in activated protein C and endothelial protein C receptor signaling. Prompt recognition of ARN is critical, as it is associated with accelerated progression of chronic kidney disease, and significant increases in short-term and long-term all-cause mortality. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies suggest that it can also occur in patients taking novel oral anticoagulants. Differences in the incidence and severity of ARN between patients taking warfarin and those taking novel oral anticoagulants are unknown; a post hoc analysis of routinely reported adverse renal outcomes in clinical trials comparing warfarin and novel oral anticoagulants found no significant difference in the rates of AKI, a prerequisite for ARN. Given the significant impact of ARN on renal function and all-cause mortality, a thorough understanding of the pathophysiology, molecular mechanisms, clinical spectrum and therapeutic interventions for ARN is crucial to balance the risks and benefits of anticoagulation and optimize treatment.

  17. New Anticoagulants for the Prevention and Treatment of Venous Thromboembolism

    PubMed Central

    McRae, Simon J; Ginsberg, Jeffrey S

    2005-01-01

    Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety), ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism. PMID:17319097

  18. Antiplatelet and Anticoagulant Drugs in Interventional Radiology

    SciTech Connect

    Altenburg, Alexander; Haage, Patrick

    2012-02-15

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

  19. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

    PubMed

    Garcia, David A; Baglin, Trevor P; Weitz, Jeffrey I; Samama, Meyer Michel

    2012-02-01

    This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT. PMID:22315264

  20. D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy.

    PubMed

    Siegbahn, Agneta; Oldgren, Jonas; Andersson, Ulrika; Ezekowitz, Michael D; Reilly, Paul A; Connolly, Stuart J; Yusuf, Salim; Wallentin, Lars; Eikelboom, John W

    2016-05-01

    Coagulation markers may improve monitoring the risk of stroke and bleeding in patients with atrial fibrillation (AF) during anticoagulant treatment. We examined baseline levels of D-dimer and their association with stroke, cardiovascular death and major bleeding in 6,202 AF patients randomised to dabigatran or warfarin in the RE-LY trial. The effects of treatment on serial levels of D-dimer and coagulation factor (F) VIIa in 2,567 patients were also analysed. Baseline D-dimer levels were related to the rate of stroke/systemic embolism (SEE) with 0.64 % in the lowest quartile (Q1, as reference) (D-dimer < 298 µg/l), 1.38 % Q2 (D-dimer 298-473 µg/l), 1.71 % Q3 (D-dimer 474-822 µg/l) and 2.00 % in Q4 (D-dimer > 822 µg/l) (p=0.0007). Similar associations were shown for cardiovascular death and major bleeding. Addition of baseline D-dimer to established clinical risk factors improved prediction of stroke/SEE, cardiovascular death and major bleeding (C-index increased from 0.66 to 0.68, 0.71 to 0.73 and 0.66 to 0.67, respectively). Dabigatran provided a greater reduction of D-dimer levels than warfarin regardless of baseline anticoagulant treatment. On-treatment levels of FVIIa were markedly reduced by warfarin (median 12.1-13.8 mU/ml) but significantly higher with dabigatran (median 39.4-49.0 mU/ml) at all-time points. Dabigatran is associated with greater reduction in D-dimer without the pronounced reduction of FVIIa seen with warfarin. These different effects on the coagulation system might explain the better efficacy and less intracranial bleeding observed with dabigatran compared with warfarin.

  1. Shock wave lithotripsy in patients requiring anticoagulation or antiplatelet agents.

    PubMed

    Alsaikhan, Bader; Andonian, Sero

    2011-02-01

    Extracorporeal shockwave lithotripsy (SWL) remains the only truly minimally invasive procedure for the treatment of upper tract nephrolithiasis. Recently, there has been a recent rise in the patients on antiplatelet agents. Therefore, the aim of the present study is to review the literature available regarding SWL in these high-risk patients requiring anti-coagulation therapy. Alternative therapies to SWL are also presented.

  2. Citrate anticoagulation in the ICU: the Leeds experience.

    PubMed

    Trumper, Charlotte

    2016-09-01

    Continuous renal replacement therapy (CRRT) is widely used in the management of critically ill patients with acute kidney injury. It requires effective anticoagulation of the extracorporeal blood circuit. Although heparin is the most commonly prescribed anticoagulant, there are issues associated with heparin, and there has been increasing interest in regional citrate anticoagulation as an alternative. In 2013, The Leeds Teaching Hospitals NHS Trust switched from heparin to citrate anticoagulant for CRRT in intensive care units (ICUs) across the Trust. This article examines the reasons for the switch, the implementation of citrate and the impact of this quality-improvement project in terms of patient outcome data and feedback from the ICU nursing team. PMID:27615524

  3. [Genetic predisposition to bleeding during oral anticoagulants treatment].

    PubMed

    Montes Díaz, R; Nantes, O; Molina, E; Zozaya, J; Hermida, J

    2008-01-01

    The degree of anticoagulation obtained during oral anticoagulation therapy with vitamin K antagonists (VKA) varies among patients due to individual and environmental factors. The rate of anticoagulation influences the hemorrhagic risk. Therefore, it is plausible that patients specially sensitive to oral anticoagulants are at higher hemorrhagic risk, specially during the first weeks. The role of a series of polymorphisms of the enzymes involved in the metabolism of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high portion of the variability observed in the sensitivity to AVK. Although the available literature suggests that these genetic variants could increase the risk of severe hemorrhage, larger, well designed studies are needed to confirm this notion.

  4. Direct oral anticoagulants: integration into clinical practice

    PubMed Central

    Cowell, Richard P W

    2014-01-01

    The introduction of direct oral anticoagulants (OACs) for the treatment and prevention of thromboembolic disease represents a shift from the traditional vitamin K antagonist-based therapies, which have been the mainstay of treatment for almost 60 years. A challenge for hospital formularies will be to manage the use of direct OACs from hospital to outpatient settings. Three direct OACs—apixaban, dabigatran and rivaroxaban—are widely approved across different indications, with rivaroxaban approved across the widest breadth of indications. A fourth direct OAC, edoxaban, has also completed phase III trials. Implementation of these agents by physicians will require an understanding of the efficacy and safety profile of these drugs, as well as an awareness of renal function, comedication use, patient adherence and compliance. Optimal implementation of direct OACs in the hospital setting will provide improved patient outcomes when compared with traditional anticoagulants and will simplify the treatment and prevention of thromboembolic diseases. PMID:25012514

  5. Anticoagulation with recombinant hirudin and danaparoid sodium in pediatric patients.

    PubMed

    Severin, Thomas; Zieger, Barbara; Sutor, Anton H

    2002-10-01

    Patients receiving heparin are at risk of developing heparin-induced thrombocytopenia (HIT). Whereas in HIT I only reversible mild thrombocytopenia occurs within the first days of heparin treatment, HIT II may lead to potentially life-threatening thromboembolic events. Pediatric patients suffering from HIT II have been reported in a study on newborns and in a few reports on children and adolescents. However, thrombotic complications can be as severe in children as they are in adults. In the case of HIT II, the withdrawal of heparin is required and alternative anticoagulation should be started. In contrast to numerous investigations in adult patients, including prospective studies, experience with alternative anticoagulants in pediatric patients is limited. The available data were analyzed according to HIT II complications, alternative anticoagulation, and clinical outcome. In conclusion, HIT II represents a potentially dangerous complication of heparin therapy in pediatric patients also. Alternative anticoagulation applied in pediatric patients mainly included danaparoid sodium and recombinant hirudin. In most patients treated with these anticoagulants, effective anticoagulation and clinical improvement were observed. Because of limited experience, more data are required for optimal management of HIT II in young patients. PMID:12420240

  6. Novel oral anticoagulants in development: Dabigatran, Rivaroxaban, and Apixaban.

    PubMed

    Sattari, Maryam; Lowenthal, David T

    2011-07-01

    Venous thromboembolic disease, including deep vein thrombosis and pulmonary embolism, is a cause of significant mortality and morbidity. For several decades, anticoagulant options for the treatment and prevention of thrombosis have been limited mainly to agents such as unfractionated heparin and oral vitamin K antagonists, such as warfarin. Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clinical practice. A variety of novel anticoagulants with improved pharmacologic and clinical profiles are in development, offering benefits over traditional therapies. Specifically, progress has been made in the development of small molecule factor Xa inhibitors and thrombin inhibitors. With their potentially consistent and predictable clinical profile, oral formulation, and decreased need for coagulation monitoring, these new agents will likely increase the use and duration of anticoagulation treatment in thromboembolic disorders and reduce the burden associated with long-term management. PMID:20535013

  7. [New oral anticoagulants in atrial fibrillation].

    PubMed

    Veltkamp, R; Hacke, W

    2011-02-01

    Atrial fibrillation (AF) causes at least 20% of all ischemic strokes. In large randomized trials of primary and secondary stroke prevention, anticoagulation with vitamin K antagonists (VKA) protected much more efficiently than antiplatelet agents against stroke. Because of the problematic pharmacological properties of VKA only part of the AF patients are currently being treated with oral anticoagulants (OAK). The targeted development of specific oral inhibitors of the central coagulation factors thrombin and factor Xa allows reliable anticoagulation without regular coagulation monitoring. In the present review, pharmacological properties of the different agents are compared. Of the four large randomized phase 3 studies in AF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) with the primary efficacy endpoint stroke and systemic embolism, the published data from the RELY trial indicate a superior efficacy of dabigatran etexilate (2 × 150 mg/day) and a lower risk of intracranial hemorrhage compared to warfarin. Favorable preliminary results have been demonstrated for the factor Xa inhibitor rivaroxaban. Apixaban was more efficacious than ASA and had a similar risk of hemorrhage in the AVERROES study. Thus, the available data suggest a favorable benefit-risk ratio for the new substances in addition to improved patient comfort. Currently unresolved issues relate to the verification of patient adherence by suitable coagulation tests and to the emergency coagulation diagnostics and therapy in acute ischemic or hemorrhagic strokes under the new OAC. PMID:21286676

  8. Antithrombotic therapy use in patients with atrial fibrillation before the era of non-vitamin K antagonist oral anticoagulants: the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) Phase I cohort

    PubMed Central

    Huisman, Menno V.; Ma, Chang Sheng; Diener, Hans-Christoph; Dubner, Sergio J.; Halperin, Jonathan L.; Rothman, Kenneth J.; Teutsch, Christine; Schoof, Nils; Kleine, Eva; Bartels, Dorothee B.; Lip, Gregory Y.H.

    2016-01-01

    Aims The introduction of non-VKA oral anticoagulants (NOACs), which differ from the earlier vitamin K antagonist (VKA) treatments, has changed the approach to stroke prevention in atrial fibrillation (AF). GLORIA-AF is a prospective, global registry programme describing the selection of antithrombotic treatment in newly diagnosed AF patients at risk of stroke. It comprises three phases: Phase I, before the introduction of NOACs; Phase II, during the time of the introduction of dabigatran, the first NOAC; and Phase III, once NOACs have been established in clinical practice. Methods and results In Phase I, 1063 patients were eligible from the 1100 enrolled (54.3% male; median age 70 years); patients were from China (67.1%), Europe (EU; 27.4%), and the Middle East (ME; 5.6%). The majority of patients using VKAs had high stroke risk (CHA2DS2-VASc ≥ 2; 86.5%); 13.5% had moderate risk (CHA2DS2-VASc = 1). Vitamin K antagonist use was higher for persistent/permanent AF (47.7%) than that for paroxysmal (23.9%). Most patients in China were treated with antiplatelet agents (53.7%) vs. 27.1% in EU and 28.8% in ME. In China, 25.9% of patients had no antithrombotic therapy, vs. 8.6% in EU and 8.5% in ME. Conclusion Phase I of GLORIA-AF shows that VKAs were mostly used in patients with persistent/permanent (vs. paroxysmal) AF and in those with high stroke risk. Furthermore, there were meaningful geographical differences in the use of VKA therapy in the era before the availability of NOACs, including a much lower use of VKAs in China, where most patients either received antiplatelet agents or no antithrombotic treatment. PMID:27335063

  9. The use of anticoagulation in pediatric cardiac disease

    PubMed Central

    Boris, JR; Harris, MA

    2003-01-01

    Palliation and repair of increasingly complex congenital heart defects as well as the emergence of novel contexts has led to multiple scenarios in which a real or potential risk of thromboembolism may exist. While various anticoagulation methodologies have been well defined for adults, there are few studies relating directly to pediatric patients. This article reviews a number of specific pediatric disease states, the representative pediatric literature, and, where appropriate, the corresponding adult literature. In so doing, the art and science of pediatric cardiac anticoagulation is defined with the hope to engender further thought regarding future directions of study and therapy. PMID:22368628

  10. Regulatory Impact on Thrombosis Treatment, Prevention, and Anticoagulant Use.

    PubMed

    Dannemiller, Robert; Ward, Tucker; Fanikos, John

    2016-10-01

    Thromboembolism afflicts millions of patients annually in the United States and is associated with a significant cost burden. Oral anticoagulants provide clinicians with options for management of these diseases and their use continues to grow. Accordingly, regulatory, legislative, and nonprofit organizations have set performance standards with the goal of improving patient outcomes, ensuring patient safety, and reducing costs. Recent efforts in quality improvement have introduced changes surrounding regulatory requirements, surveillance, litigation, and oversight that clinicians should be familiar with. This article summarizes key updates related to the management of anticoagulant therapy as it relates to thrombosis prevention and treatment. PMID:27637311

  11. Femoral neuropathy due to retroperitoneal bleeding. A red herring in medicine complicates anticoagulant therapy and influences the Russian Communist Revolution (Crown Prince Alexis, Rasputin).

    PubMed

    Willbanks, O L; Willbanks, S E

    1983-02-01

    Femoral neuropathy occurs when occult retroperitoneal bleeding impinges on the appropriate nerve roots. The syndrome involves the acute onset of groin and thigh pain with characteristic flexion and external rotation of the hip. It may mimic other conditions such as acute arterial occlusion. Thorough knowledge of the anatomy of the femoral nerve explains the clinical features and leads the clinician to suspect the occurrence of this syndrome. Three cases have been reviewed that exhibited this condition as a result of retroperitoneal bleeding, a complication of systemic heparin therapy. The hemophilia that afflicted Alexis, the Crown Prince of Russia and son of Tsar Nicholas and Tsarina Alexandra, resulted in this clinical syndrome. The consequences enabled the sinister starets, Gregory Rasputin, to become intimately involved with the royal family, influencing the response of the Tsar to the political events in Russia, thereby playing an important role in setting the stage for the 1917 Russian communist revolution.

  12. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    PubMed Central

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

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR <2 was 29.1% and the mean time with an INR >3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

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

    PubMed Central

    Hu, Tiffany Y; Vaidya, Vaibhav R; Asirvatham, Samuel J

    2016-01-01

    Novel oral anticoagulants (NOACs) are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075) is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran), a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445) and ciraparantag (PER977) are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials. PMID:26937198

  14. Anticoagulation in atrial fibrillation. Is there a gap in care for ambulatory patients?

    PubMed Central

    Putnam, Wayne; Nicol, Kelly; Anderson, David; Brownell, Brenda; Chiasson, Meredith; Burge, Frederick I.; Flowerdew, Gordon; Cox, Jafna

    2004-01-01

    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 not taking warfarin who had risk factors that made anticoagulation appropriate. MAIN OUTCOME MEASURES: Proportion of patients removed from the care gap; reasons given for not giving the remainder anticoagulants. RESULTS: Half the patients thought to be in the care gap had previously unknown contraindications to anticoagulation, lacked a clear indication for anticoagulation, or were taking warfarin. Patients' refusal and anticipated problems with compliance and monitoring were among the reasons for not giving patients anticoagulants. CONCLUSION: Adding data from primary care physicians significantly narrowed the care gap. Attention should focus on the remaining reasons for not giving eligible patients anticoagulants. PMID:15508374

  15. Development of an anticoagulation stewardship program at a large tertiary care academic institution.

    PubMed

    Padron, Maria; Miyares, Marta A

    2015-02-01

    Pharmacist-directed anticoagulation management services (AMSs) have been shown to significantly lower anticoagulation-related mortality, length of hospital stay, bleeding complications, blood transfusion requirements, and cost of therapy. AMSs are only 1 component of an anticoagulation stewardship program. Frequently, stewardship programs are limited to inpatient populations. Incorporating components that facilitate transition to outpatient status will ideally encompass complete care. The purpose of this program was to expand anticoagulation services and standardize care by implementing a full-service stewardship program including a transition of care service. The first component of the study involved medication surveillance for inpatients on anticoagulation therapy. The second component involved transitioning patients on anticoagulation, primarily with venous thromboembolism (VTE) to outpatient management. Finally, the pharmacist identified areas for optimization. Optimization involved developing or updating protocols to reflect updates in the literature as well as updating institution-specific information resources. Interventions made through medication surveillance and utilization of the VTE transition of care services translated into a total cost savings of approximately US$270 320. A postgraduate, first-year pharmacy resident contributed to improving patient outcomes while reducing utilization of hospital services and obtaining substantial cost savings through participation in anticoagulation stewardship services.

  16. Anticoagulation in Atrial Fibrillation – Current Concepts

    PubMed Central

    Katritsis, Demosthenes G; Gersh, Bernard J; Camm, A John

    2015-01-01

    This article presents the current status of the use of anticoagulation for the treatment of AF, particularly with the use of non-vitamin K-dependent anticoagulants. Comparisons between these agents and warfarin are made and methods for assessment of anticoagulant activity and reversal are discussed. PMID:26835109

  17. Anticoagulation and delayed bowel resection in the management of mesenteric venous thrombosis.

    PubMed

    Kim, Hyung-Kee; Chun, Jae Min; Huh, Seung

    2013-08-14

    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 patients with suspected bowel ischemia. Here we describe a patient with acute mesenteric venous thrombosis who presented with bowel ischemia and was treated with anticoagulation and delayed short-segment bowel resection.

  18. New Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation: More Choices Bring More Challenges

    PubMed Central

    Howard, Patricia A.

    2013-01-01

    For patients with atrial fibrillation, anticoagulant therapy is essential to reduce the risk of ischemic stroke that is associated with this arrhythmia. Historically, warfarin has been the preferred treatment for patients at moderate to high risk despite many potential limitations. With the development of newer oral anticoagulants, clinicians now have 3 additional options: dabigatran, rivaroxaban, and apixaban. Although these agents clearly offer some advantages over warfarin, they may not be appropriate for all patients. This article will discuss factors that should be considered when selecting among these various anticoagulants. PMID:24421491

  19. Lifesaving citrate anticoagulation to bridge ineffective danaparoid [correction of to bridge to danaparoid] treatment.

    PubMed

    Dworschak, Martin; Hiesmayr, Jörg Michael; Lassnigg, Andrea

    2002-05-01

    A case of successful regional anticoagulation with trisodium citrate in a patient who developed heparin-induced thrombocytopenia while on continuous hemofiltration is described. Immediate citrate anticoagulation allowed for maintenance of extracorporeal circulation until effective danaparoid therapy could be established. Recommended plasma antifactor Xa levels for hemodialysis may be inadequate in some cases. Values similar to those in use during cardiopulmonary bypass could be required. PMID:12022563

  20. Safe per-operative anticoagulation

    PubMed Central

    Wieberdink, J.

    1967-01-01

    Pre-, per-, and post-operative anticoagulation at the therapeutic level is nowadays the most, if not the only, available effective method to prevent post-operative thrombo-embolism. There is no increased tendency to bleeding to be feared during the operation. The real danger of this prophylaxis consists of a treacherous tendency to acute relative overdosage after the operation. This is explained by the combined indirect action of anticoagulants and influences related to the operation. As its development can accurately be followed by laboratory tests, dangerous levels of anticoagulation can be prevented. Experiences in 242 surgical patients are presented to demonstrate the efficacy of the following post-operative routine: Coagulation studies (prothrombin time or thrombotest) at least twice daily during one week; fractionated administration of anticoagulants and, if necessary, small amounts (0·25-1 mg.) of vitamin K1. The results suggest that with this policy the risk of thrombo-embolism in surgery can be considerably reduced, if not abolished. Images PMID:6076513

  1. [New oral anticoagulants - influence on coagulation tests].

    PubMed

    Simeon, L; Nagler, M; Wuillemin, W A

    2014-01-01

    The new oral anticoagulants (NOACs) represent alternative antithrombotic agents for prophylaxis and therapy of thromboembolic diseases. They act either by inhibition of the clotting factor Xa or IIa (thrombin). As a consequence, they influence several coagulation assays (for example prothrombin time, activated partial thromboplastin time). Because of the short half-life of these new agents, these changes show great variations in the course of 24 hours. Furthermore, there are significant differences of laboratory results depending on the used reagents. We explain the influence of apixaban, rivaroxaban (factor Xa inhibitors) and dabigatran (thrombin inhibitor) on the most commonly used coagulation assays. Besides we show that this influence depends on the way of action of the drug as well as on the principle of the coagulation assay. Being aware of this relationships helps to interpret the results of coagulation assays under influence of NOACs correctly.

  2. Treatment of Venous Thromboembolism With New Anticoagulant Agents.

    PubMed

    Becattini, Cecilia; Agnelli, Giancarlo

    2016-04-26

    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

  3. Contact laser prostatectomy in a patient on chronic anticoagulation

    NASA Astrophysics Data System (ADS)

    Mueller, Edward J.

    1995-05-01

    The `gold standard' therapy for patients with symptomatic bladder outlet obstruction secondary to benign prostatic hyperplasia has always been electrocautery TURP. However, in patients with medical problems requiring chronic anticoagulation, this procedure is contraindicated due to the extreme risk of hemorrhage, both during the procedure and the immediate post operative period. With the recent development of contact laser prostatectomy the patient on chronic anticoagulation can safely undergo the procedure. Herein, I present a case of a 60 year old with significant bladder outlet obstruction yielding an AUA symptom score of 18. The patient had a history of multiple episodes of deep venous thrombosis of the left leg with three prior pulmonary emboli. He was maintained on chronic anticoagulation with alternating days of 3.5 mg. and 5.0 mg. of warfarin sodium (coumadin). Preoperative cystoscopy showed a 4 cm prostatic fossa obstructed by tri-lobar hypertrophy, with large kissing lateral lobes and visual obstruction from the verumontanum. The patient underwent a contact laser prostatectomy with the SLT Nd:YAG laser at 50 watts. There was minimal bleeding both during the procedure and in the immediate postoperative period. At three months post-op the AUA symptom score had decreased to 2. This case demonstrated that contact laser prostatectomy can be safely and effectively performed in patients on chronic anticoagulation.

  4. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived.

  5. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived. PMID:26945262

  6. Point-of-care monitoring of oral anticoagulation therapy in children. Comparison of the CoaguChek XS system with venous INR and venous INR using an International Reference Thromboplastin preparation (rTF/95).

    PubMed

    Greenway, Anthea; Ignjatovic, Vera; Summerhayes, Robyn; Newall, Fiona; Burgess, Janet; DeRosa, Lydia; Monagle, Paul

    2009-07-01

    Point-of-care (POC) monitoring of oral anticoagulation has been widely adopted in both paediatric and adult patients. A new POC system, the CoaguChek XS has recently been developed to measure the international normalised ratio (INR) and may offer significant advantages. The CoaguChek XS utilises a new method of electrochemical clot detection based on thrombin generation. This system has not been previously evaluated in children with reference to the laboratory gold standard, the prothrombin time using reference thromboplastin. It was the objective to compare values obtained by the CoaguChek XS system with both the venous INR and the gold standard for anticoagulant monitoring, prothrombin time with reference thromboplastin (rTF/95). To evaluate the impact of testing using the CoaguChek XS on clinical anticoagulant dosing decisions. Fifty paired venous INR and capillary CoaguChek XS results were obtained from 31 children (aged up to 16 years). The laboratory gold standard, a manual prothrombin time with reference thromboplastin (rTF/95) was additionally performed on 26 samples. Correlation between the CoaguChek XS result and the venous INR was r = 0.810. Agreement between the CoaguChek XS result and the reference INR was shown to be higher (r=0.95), in the subset analysed by this method. Correlation between the venous INR and reference INR was r=0.90. Despite changes to the methodology of testing with the CoaguChek XS POC monitoring system, the accuracy of this method when compared with both the venous INR and gold standard reference INR was satisfactory. This resulted in infrequent changes to clinical decision making regarding anticoagulation.

  7. A Comprehensive Overview of Direct Oral Anticoagulants for the Management of Venous Thromboembolism.

    PubMed

    Comerota, Anthony J; Ramacciotti, Eduardo

    2016-07-01

    Venous thromboembolism (VTE) is a prevalent, potentially fatal health problem. Although standard anticoagulant therapy is effective when compared with the newer direct oral anticoagulants (DOACs), it has disadvantages. Heparin and its derivatives must be administered parenterally, whereas use of oral vitamin K antagonists is complicated by unpredictable pharmacokinetics and pharmacodynamics, drug-food and drug-drug interactions and the requirement for frequent laboratory monitoring. Randomized phase 3 trials have demonstrated that patients receive similarly effective anticoagulation with the DOACs dabigatran, edoxaban, rivaroxaban and apixaban when compared with warfarin, with similar or reduced risk of bleeding. Extended therapy trials have consistently demonstrated superior effectiveness for DOAC treatment when compared with placebo in preventing VTE recurrence. This article presents a comprehensive review of the pharmacokinetics, pharmacodynamics and accumulated clinical trial evidence for each DOAC for short-term, long-term and extended VTE therapy, and it considers the potential implications these agents have for the clinical management of VTE. PMID:27432042

  8. Anticoagulation-associated adverse drug events

    PubMed Central

    Piazza, Gregory; Nguyen, Thanh Nha; Cios, Deborah; Labreche, Matthew; Hohlfelder, Benjamin; Fanikos, John; Fiumara, Karen; Goldhaber, Samuel Z.

    2011-01-01

    Purpose Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a five-year retrospective study at Brigham and Women’s Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated adverse drug events (ADEs). Methods We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Women’s Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data regarding the cost associated with hospitalizations in which ADRs occurred. Results Of 463 anticoagulant-associated ADEs, 226 were MEs (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean $33,189 per ADR) followed by pharmacy costs (mean $7,451 per ADR). Conclusion Most anticoagulant-associated ADEs among inpatients result from medication errors and are therefore potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further Quality Improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures. PMID:22114827

  9. The target-specific oral anticoagulants: practical considerations.

    PubMed

    Garcia, David A

    2014-12-01

    More than 4 years have passed since the first approval of a target-specific oral anticoagulant (TSOAC) in the United States, and the number of clinicians who have prescribed (or considered prescribing) one or more of these medications is increasing. Although these agents may, in properly selected patients, offer advantages over more traditional therapies, their lack of familiarity can be intimidating. Clinicians who are prescribing the TSOACs face a number of management questions not definitively answered by the registration trials. This chapter reviews some of these situations, including updated information on the periprocedural management of TSOACs and the latest evidence about how to best measure TSOAC effect. The lack of an antidote and other considerations that may be relevant when deciding between newer and more traditional anticoagulant medications are also discussed.

  10. Novel Anticoagulants in Atrial Fibrillation: Monitoring, Reversal and Perioperative Management

    PubMed Central

    Shamoun, Fadi; Obeid, Hiba; Ramakrishna, Harish

    2015-01-01

    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. Both United States and European Guidelines recommend NOACs for stroke prevention in patients with atrial fibrillation. This review discusses each of the NOACs, along with their efficacy and safety data. It explores the most recent guidelines regarding their perioperative use in atrial fibrillation patients. It also discusses bleeding complications, perioperative management, and reversal agents. PMID:26221593

  11. Direct oral anticoagulants and venous thromboembolism.

    PubMed

    Franchini, Massimo; Mannucci, Pier Mannuccio

    2016-09-01

    Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE. PMID:27581829

  12. Secondary poisoning of owls by anticoagulant rodenticides

    USGS Publications Warehouse

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

    1980-01-01

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

  13. Rationale for Development of New Oral Anticoagulants.

    PubMed

    Akin, Muharrem; Widder, Julian; Akin, Ibrahim; Brehm, Michael; Schäfer, Andreas

    2015-01-01

    The development of new or direct oral anticoagulants was triggered by the disadvantages of classic oral anticoagulation, which was isolated in Link's laboratory in 1940. Some of these limitations are the individual variation in response to these drugs, drug interaction and the need for regular laboratory monitoring. With increasing comorbidity and life expectancy in populations these limitations led to interruption of treatment or even underuse of treatment in light of potential side effects. With the introduction of novel oral anticoagulants some of these drawbacks are targeted whereas even these drugs also have some limitations and should be given with cautions and not to all patients having an indication for anticoagulation.

  14. Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia.

    PubMed

    Demers, C; Ginsberg, J S; Brill-Edwards, P; Panju, A; Warkentin, T E; Anderson, D R; Turner, C; Kelton, J G

    1991-11-01

    In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin-induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.

  15. Non-traumatic compartment syndrome secondary to deep vein thrombosis and anticoagulation.

    PubMed

    Newman, Peter Alexander; Deo, Sunny

    2014-01-01

    We describe an unusual case of non-traumatic compartment syndrome in three compartments of the left lower limb in a 57-year-old male inpatient. He had recently been started on anticoagulation therapy for multiple pulmonary emboli and deep vein thrombosis of the left posterior tibial and peroneal veins. Three of the four osteofascial compartments had pressures above 70 mm Hg, hence four compartment fasciotomies were performed. Postoperatively, intravenous heparin therapy was started resulting in a significant blood loss, but he had no neurovascular deficit. At reoperation, for primary wound closure, his tissues looked healthy. Non-traumatic causes of acute compartment syndrome, including deep venous thrombosis and anticoagulation, are considered.

  16. Improving the quality of anticoagulation of patients with atrial fibrillation in managed care organizations: results of the managing anticoagulation services trial.

    PubMed

    Matchar, David B; Samsa, Gregory P; Cohen, Stuart J; Oddone, Eugene Z; Jurgelski, Annette E

    2002-07-01

    Randomized trials have indicated that well-managed anticoagulation with warfarin could prevent more than half of the strokes related to atrial fibrillation. However, many patients with atrial fibrillation who are eligible for this therapy either do not receive it or are not maintained within an optimal prothrombin time-international normalized ratio (INR) range. We sought to determine whether an anticoagulation service within a managed care organization would be a feasible alternative for providing anticoagulation care. We performed a multi-site randomized trial in six large managed care organizations in the United States. Subjects were aged 65 years or older and had nonvalvular atrial fibrillation. At each site, physician practices were divided into two geographically defined practice clusters; each site was randomly assigned to have one intervention and one control cluster. The intervention cluster received an anticoagulation service that satisfied specifications for high-quality anticoagulation care and was coordinated through the managed care organization. Control clusters continued with their usual provider-based care. We measured the proportion of time that warfarin-treated patients in each of the clusters (intervention and control) were in the target range for the INR at baseline, and again during a follow-up period. Five of the six selected sites succeeded at developing an anticoagulation service. Patients in the intervention and control clusters had similar demographic characteristics, contraindications to warfarin, and risk factors for stroke. Among patients (n = 144 in the intervention clusters; n = 118 in the control clusters) for whom data were available during the baseline and follow-up periods, the changes in percentages of time in the target range were similar for those in the intervention clusters (baseline: 47.7%; follow-up: 55.6%) and in the control clusters (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95% confidence interval: -5

  17. Poly(γ-glutamic acid), coagulation? Anticoagulation?

    PubMed

    Xu, Tingting; Peng, Fang; Zhang, Tao; Chi, Bo; Xu, Hong; Mao, Chun; Feng, Shuaihui

    2016-11-01

    Poly(γ-glutamic acid) (γ-PGA) powder was usually used as hemostatic agent because of its excellent physical properties of water-absorption and water-locking. However, if γ-PGA absorbs enough water, how about its blood compatibility? Here, the other side of the coin was investigated. The anticoagulant properties of γ-PGA were characterized by in vitro coagulation tests, hemolytic assay, platelet adhesion, and platelet activation. Moreover, cytotoxicity experiments of γ-PGA were also carried out by MTT assay. Results indicated that the sufficient water-absorbed γ-PGA has good anticoagulant property and non-cytotoxicity. It means γ-PGA has good anticoagulant property, non-cytotoxicity. If γ-PGA has absorbed enough water, it can be used as an anticoagulation biomaterial. With double effects (coagulation and anticoagulation), the γ-PGA with desirable bioproperties can be readily tailored to cater to various biomedical applications. PMID:27545694

  18. Anticoagulation management associated with extracorporeal circulation.

    PubMed

    Sniecinski, Roman M; Levy, Jerrold H

    2015-06-01

    The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass.

  19. Telephone-based anticoagulation management in the homebound setting: a retrospective observational study

    PubMed Central

    Hassan, Samer; Naboush, Ali; Radbel, Jared; Asaad, Razan; Alkaied, Homam; Demissie, Seleshi; Terjanian, Terenig

    2013-01-01

    Background Anticoagulation management is currently performed through anticoagulation clinics or self-managed with or without the help of medical services. Homebound patients are a unique population that cannot utilize anticoagulation clinics or self-testing. Telephone-based anticoagulation management could be an alternative to the traditional methods of monitoring warfarin in this subgroup. The objective of this retrospective, observational study is to investigate the feasibility of warfarin management in homebound patients. Methods This study was performed through the use of telephone-based adjustments of warfarin dose based on an international normalized ratio (INR) result. Four hundred forty-eight homebound patients referred to the anticoagulation clinic at Staten Island University Hospital were visited at home by a phlebotomist; a blood sample was drawn for initial laboratory testing. A nurse practitioner then called the patient or designated person to relay the INR result and to direct dosage adjustment. INR results and dosage changes were entered into an electronic medical record and analyzed statistically. Results The mean percentage of INR values in range was 58.39%. The mean time when the INR was in the therapeutic range was 62.75%. The percent of patients who were therapeutically controlled decreased as the number of medications increased. The complication rate was 4% per patient year, with an equal distribution between bleeding and clotting. These values compared favorably to other studies in which monitoring was performed through anticoagulation clinics or self-monitoring. The cost per visit at our anticoagulation clinic was found to be approximately $300 compared with $82 when utilizing our homebound service. Conclusion Telephone-based management of warfarin therapy in the homebound setting is feasible. It can lower the cost of health care expenditures compared to other modalities of anticoagulation management. PMID:24348065

  20. Anticoagulants

    MedlinePlus

    ... or interactions with other medicines and vitamin or herbal supplements. This information should not be used as medical ... your doctor about every medicine and vitamin or herbal supplement that you are taking, so he or she ...

  1. Anticoagulation

    MedlinePlus

    ... gums or nosebleeds. Oral Medications These mainly include aspirin or clopidogrel (Plavix) and warfarin (Coumadin). These medications ... will decide which one is right for you. Aspirin tends to cause fewer bleeding complications than clopidogrel ...

  2. The in-vitro anticoagulant effect of rivaroxaban in neonates.

    PubMed

    Attard, Chantal; Monagle, Paul; Kubitza, Dagmar; Ignjatovic, Vera

    2014-04-01

    The use of anticoagulants in neonates is increasing because of the medical advances improving the long-term survival of very sick infants who are at risk of venous thromboembolism (VTE). Current anticoagulation therapy in neonates is less than ideal, because of the physiological differences compared to children and adults regarding the pathophysiology of thrombosis and pharmacology of the drug. Limitations associated with conventional anticoagulants have prompted the development of novel drugs that specifically target the key proteins in the coagulation system. Rivaroxaban is the first oral, direct Factor Xa inhibitor available for the prevention of VTE in adults. Its predictable pharmacokinetic profile, high oral bioavailability and once-daily dosing make rivaroxaban an optimal anticoagulant that warrants investigation in neonates. This study was designed to determine whether there are age-related differences in the pharmacodynamic effects of rivaroxaban in vitro amongst neonates. Neonatal and adult plasma pools were created and spiked with increasing concentrations of rivaroxaban (0-500 ng/ml). Commercially available prothrombin time (PT), activated partial thromboplastin time (aPTT) and anti-Factor Xa assays as well as a sub-sampling thrombin generation assay were used to measure the rivaroxaban effect. A dose-dependent response was observed for PT, aPTT and lag time in both the age groups. Rivaroxaban caused a significant increase in the clotting time for PT and aPTT as well as an increase in lag time (as measured by thrombin generation) in neonates when compared with adults. In-vivo studies are required to confirm the consistency of dose-response in neonates. PMID:24418940

  3. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states.

    PubMed Central

    Vigano D'Angelo, S; Comp, P C; Esmon, C T; D'Angelo, A

    1986-01-01

    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. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals. PMID:3511097

  4. Gastrointestinal bleeding and anticoagulant or antiplatelet drugs: systematic search for clinical practice guidelines.

    PubMed

    Gutermann, Irit Kaye; Niggemeier, Verena; Zimmerli, Lukas U; Holzer, Barbara M; Battegay, Edouard; Scharl, Michael

    2015-01-01

    Gastrointestinal (GI) bleeding is a frequently encountered and very serious problem in emergency room patients who are currently being treated with anticoagulant or antiplatelet medications. There is, however, a lack of clinical practice guidelines about how to respond to these situations. The goal of this study was to find published articles that contain specific information about how to safely adjust anticoagulant and antiplatelet therapy when GI bleeding occurs.The investigators initiated a global search on the PubMed and Google websites for published information about GI bleeding in the presence of anticoagulant or antiplatelet therapy. After eliminating duplicate entries, the medical articles that remained were screened to narrow the sets of articles to those that met specific criteria. Articles that most closely matched study criteria were analyzed in detail and compared to determine how many actual guidelines exist and are useful.We could provide only minimal information about appropriate therapeutic strategies because no articles provided sufficient specific advice about how to respond to situations involving acute GI bleeding and concurrent use of anticoagulant or antiplatelet drugs. Only 4 articles provided enough detail to be of any use in an emergency situation.Clinical practice guidelines and also clinical trials for GI hemorrhaging should be expanded to state in which situations the use of anticoagulant or antiplatelet drugs should be suspended and the medications should later be resumed, and they should state the level of risk for any particular action.

  5. Adherence to long-term anticoagulation treatment, what is known and what the future might hold.

    PubMed

    Abdou, John K; Auyeung, Vivian; Patel, Jignesh P; Arya, Roopen

    2016-07-01

    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.

  6. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism.

    PubMed

    Smythe, Maureen A; Priziola, Jennifer; Dobesh, Paul P; Wirth, Diane; Cuker, Adam; Wittkowsky, Ann K

    2016-01-01

    Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. Despite the changing landscape of VTE treatment with the introduction of the new direct oral anticoagulants many uncertainties remain regarding the optimal use of traditional parenteral agents. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. This specific chapter addresses the practical management of heparins including low molecular weight heparins and fondaparinux. For each anticoagulant a list of the most common practice related questions were created. Each question was addressed using a brief focused literature review followed by a multidisciplinary consensus guidance recommendation. Issues addressed included initial anticoagulant dosing recommendations, recommended baseline laboratory monitoring, managing dose adjustments, evidence to support a relationship between laboratory tests and meaningful clinical outcomes, special patient populations including extremes of weight and renal impairment, duration of necessary parenteral therapy during the transition to oral therapy, candidates for outpatient treatment where appropriate and management of over-anticoagulation and adverse effects including bleeding and heparin induced thrombocytopenia. This article concludes with a concise table of clinical management questions and guidance recommendations to provide a quick reference for the practical management of heparin, low molecular weight heparin and fondaparinux.

  7. Direct oral anticoagulants: key considerations for use to prevent stroke in patients with nonvalvular atrial fibrillation

    PubMed Central

    Ment, Jerome

    2015-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Strokes that occur as a complication of AF are usually more severe and associated with a higher disability or morbidity and mortality rate compared with non-AF-related strokes. The risk of stroke in AF is dependent on several risk factors; AF itself acts as an independent risk factor for stroke. The combination of effective anticoagulation therapy, risk stratification (based on stroke risk scores, such as CHADS2 and CHA2DS2-VASc), and recommendations provided by guidelines is essential for decreasing the risk of stroke in patients with AF. Although effective in preventing the occurrence of stroke, vitamin K antagonists (VKAs; eg, warfarin) are associated with several limitations. Therefore, direct oral anticoagulants, such as apixaban, dabigatran etexilate, edoxaban, and rivaroxaban, have emerged as an alternative to the VKAs for stroke prevention in patients with nonvalvular AF. Compared with the VKAs, these agents have more favorable pharmacological characteristics and, unlike the VKAs, they are given at fixed doses without the need for routine coagulation monitoring. It remains important that physicians use these direct oral anticoagulants responsibly to ensure optimal safety and effectiveness. This article provides an overview of the existing data on the direct oral anticoagulants, focusing on management protocols for aiding physicians to optimize anticoagulant therapy in patients with nonvalvular AF, particularly in special patient populations (eg, those with renal impairment) and other specific clinical situations. PMID:26089678

  8. [New oral anticoagulants (NOAC) in nephrology].

    PubMed

    Bellasi, Antonio; Di Lullo, Luca; Melfa, Gianvincenzo; Minoretti, Claudio; Ratti, Carlo; Campana, Carlo; Volpi, Maurizio; Mangano, Stefano; Di Iorio, Biagio; Cozzolino, Mario

    2016-01-01

    The new or direct oral anticoagulants [new oral anticoagulants (NOAC) or direct oral anticoagulants (DOAC)] were launched in the Italian market in 2013. Although these compounds share common pharmacological indications with vitamin K antagonists (warfarin or acenocumarol), they have different mechanisms of action, do not require a constant anticoagulant monitoring but are more efficacious and safer than vitamin K antagonists. The use of these molecules (Dabigatran, Apixaban, Rivaroxaban, Betrixaban, Edoxaban) is constantly rising in daily practice. However, while available data suggest that NOAC/DOAC use is safe, dosage should be adjusted based on renal or liver function. It should be acknowledged that commonly available blood tests [Prothrombin Time (PT) and partial thromboplastin time (PTT)] are not indicated to monitor the anticoagulant activity of these compounds. With the exception of dabigatran, we currently lack of an antidote to reverse the anticoagulant effect of NOAC/DOAC. We herein review available evidence on NOAC/DOAC pharmacokinetic, risk factors for bleeding, interventions to reverse the anticoagulant activity in case of hemorrhages or need of urgent surgery and/or NOAC/DOAC overdose or side effects. PMID:27545637

  9. Intramural esophagic hematoma secondary to coumarinic anticoagulation: a case report

    PubMed Central

    2009-01-01

    Esophagic Intramural Hematoma is an uncommon clinical condition, with a prognosis which is essentially benign. On most cases, a predisposing or precipitating factor may be seen, with the most common ones being the history of esophagic instrumentation, food impactations and thrombocytopenia. In the following manuscript, the authors present the case of a 54-years-old male with history of valve replacement surgery, who was treated at the Clinica Cardiovascular (Medellin, Colombia), with a clinical case of Intramural Esophagic Hematoma that was later confirmed to be due to a Coumarinic overanticoagulation. On this case, it is evidenced that Intramural Esophagic Hematoma is an unrecognized complication of Courmarinic anticoagulation therapy. PMID:20069068

  10. Noncompaction and embolic myocardial infarction: the importance of oral anticoagulation.

    PubMed

    Pulignano, Giovanni; Tinti, Maria Denitza; Tolone, Stefano; Musto, Carmine; De Lio, Lucia; Pino, Paolo Giuseppe; Minardi, Giovanni; Violini, Roberto; Uguccioni, Massimo

    2015-01-01

    Left ventricular noncompaction (LVNC) is characterized by left ventricular (LV) hypertrabeculations and is associated with heart failure, arrhythmias and embolism. We report the case of a 67-year-old LVNC patient, under oral anticoagulation (OAC) therapy for apical thrombosis. After she discontinued OAC, the thrombus involved almost the whole of the left ventricle; in a few months her condition worsened, requiring hospitalization, and despite heparin infusion she experienced myocardial infarction (MI), caused by embolic occlusion of the left anterior descending artery. Although infrequent as a complication of LVNC, and usually attributable to microvascular dysfunction, in this case MI seems due to coronary thromboembolism from dislodged thrombotic material in the left ventricle.

  11. [Direct oral anticoagulant associated bleeding].

    PubMed

    Godier, A; Martin, A-C; Rosencher, N; Susen, S

    2016-07-01

    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

  12. [Direct oral anticoagulant associated bleeding].

    PubMed

    Godier, A; Martin, A-C; Rosencher, N; Susen, S

    2016-07-01

    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.

  13. [Prophylaxis of thromboembolism in atrial fibrillation: new oral anticoagulants and left atrial appendage closure].

    PubMed

    Zeus, Tobias; Kelm, Malte; Bode, Christoph

    2015-08-01

    Thrombo-embolic prophylaxis is a key element within the therapy of atrial fibrillation/atrial flutter. Besides new oral anticoagulants the concept of left atrial appendage occlusion has approved to be a good alternative option, especially in patients with increased risk of bleeding. PMID:26261929

  14. [Thoracic epidural analgesia (TEA) in clinical practice: effects, technique, complications and suggestions during anticoagulant treatment].

    PubMed

    Passarani, S; Pedrazzini, G; Paino, R; Paleari, G

    2001-03-01

    The effects of thoracic peridural analgesia (TEA) on the neuroendocrine response to surgery are well known, but, at the present this technique is not widely used especially in Italy. The aim of this paper is to give information and suggestions on thoracic epidural analgesia in thoracic and cardiac surgery, and to discuss how anticoagulant therapy may interfere on this technique.

  15. Use of the Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism.

    PubMed

    Riva, Nicoletta; Ageno, Walter

    2016-10-01

    In the past 2 decades, the direct oral anticoagulants (DOACs) have emerged as alternatives to the standard therapy (unfractionated or low-molecular-weight heparin followed by vitamin K antagonists [VKA]), for the acute and extended treatment of venous thromboembolism. The DOACs have a more favorable pharmacologic profile and a predictable anticoagulant response and, therefore, have the potential to overcome some of the limitations associated with the use of VKA. Several ongoing registries are evaluating the use of the DOACs in routine clinical practice and will provide additional information in less selected patient populations. PMID:27637306

  16. Efficacy and Safety of Oral Anticoagulants Versus Aspirin for Patients With Atrial Fibrillation

    PubMed Central

    Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu

    2015-01-01

    Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing

  17. Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

    PubMed Central

    Gómez-Outes, Antonio; Suárez-Gea, M Luisa; Lecumberri, Ramón; Terleira-Fernández, Ana Isabel; Vargas-Castrillón, Emilio; Rocha, Eduardo

    2013-01-01

    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 and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies. PMID:23674896

  18. New antiplatelet drugs and new oral anticoagulants.

    PubMed

    Koenig-Oberhuber, V; Filipovic, M

    2016-09-01

    In our daily anaesthetic practice, we are confronted with an increasing number of patients treated with either antiplatelet or anticoagulant agents. During the last decade, changes have occurred that make the handling of antithrombotic medication a challenging part of anaesthetic perioperative management. In this review, the authors discuss the most important antiplatelet and anticoagulant drugs, the perioperative management, the handling of bleeding complications, and the interpretation of some laboratory analyses related to these agents. PMID:27566810

  19. Anticoagulation for pediatric mechanical circulatory support.

    PubMed

    Annich, Gail; Adachi, Iki

    2013-06-01

    Extracorporeal life support applications have evolved considerably in recent years. However, the blood-biomaterial interface remains incompletely understood, and management of the acute inflammatory response and coagulation pathways continues to be challenging. At present, the gold standard for anticoagulation is unfractionated heparin. Since the inception of extracorporeal life support, the mainstay for anticoagulation monitoring has been activated clotting time. However, alongside the technological evolution in extracorporeal life support, the methods for monitoring heparin have also become more sophisticated, adding additional layers of complexity to creating an ideal safe protocol for anticoagulation during extracorporeal life support. To address this, the Extracorporeal Life Support Organization has formed an Anticoagulation Task Force to help direct both a consensus statement and potential guidelines within which the multiple monitoring methods can be customized for extracorporeal life support. One key question that remains in the use of these monitoring methods is whether the objective during extracorporeal life support is to anticoagulate the circuit to prevent thrombus formation within the extracorporeal device or whether it is to systemically anticoagulate the patient. This review details all current monitoring methods and highlights how they can be used during pediatric mechanical circulatory support. PMID:23735984

  20. Impact of smart infusion technology on administration of anticoagulants (unfractionated Heparin, Argatroban, Lepirudin, and Bivalirudin).

    PubMed

    Fanikos, John; Fiumara, Karen; Baroletti, Steve; Luppi, Carol; Saniuk, Catherine; Mehta, Amar; Silverman, Jon; Goldhaber, Samuel Z

    2007-04-01

    This study reviewed 863 alerts generated from the infusion of anticoagulants in 355 patients from October 2003 to January 2005. Alerts were generated by smart infusion technology pumps and recorded in the devices' memory. The most common alerts were underdose alerts (59.8%), followed by overdose alerts (31.3%) and duplicate drug therapy alerts (8.9%). In response to the alerts, users' most frequent action was to cancel (46.5%) or reprogram (43.1%) the infusions. The highest percentage of alerts occurred from 2 to 4 p.m. During the study, there were 4 infusion rate errors, compared with 15 in the immediately preceding 16-month period. In conclusion, smart infusion technology intercepted keypad entry errors, thereby reducing the likelihood of intravenous anticoagulant overdose or underdose. Dose or infusion rate programming during intravenous anticoagulation is an important targets for medication safety interventions.

  1. Evolving Treatments for Arterial and Venous Thrombosis: Role of the Direct Oral Anticoagulants.

    PubMed

    Chan, Noel C; Eikelboom, John W; Weitz, Jeffrey I

    2016-04-29

    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

  2. Anticoagulation, ferrotoxicity and the future of translational lung cancer research

    PubMed Central

    2016-01-01

    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

  3. Anticoagulation, ferrotoxicity and the future of translational lung cancer research.

    PubMed

    Zacharski, Leo R

    2016-06-01

    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

  4. Polysulfated Trehalose as a Novel Anticoagulant Agent with Dual Mode of Action

    PubMed Central

    Rashid, Qudsia; Abid, Mohammad; Gupta, Neha; Tyagi, Tarun; Ashraf, Mohammad Z.; Jairajpuri, Mohamad Aman

    2015-01-01

    Physiological hemostatic balance is a coordinated outcome of counteracting coagulation and fibrinolytic systems. An imbalance of procoagulant and anticoagulant factors may result in life threatening thromboembolism. Presently, anticoagulant administration is the first line of therapy for the treatment of these conditions and several anticoagulants have been approved, including various forms of heparin. However, the polyanionic nature and multispecificity of heparin pose several complications. Generally, the polysulfated compounds with antithrombotic potential are thought to have feasible synthetic procedures with much less bleeding, thus having favourable safety profiles. Here we report the synthesis of a novel compound, trehalose octasulfate and the assessment of its anticoagulation potential. Molecular docking of trehalose and trehalose octasulfate with antithrombin showed a specificity switch in binding affinity on sulfation, where trehalose octasulfate interacts with critical residues of AT that are either directly involved in heparin binding or in the conformational rearrangement of AT on heparin binding. An in vitro analysis of trehalose octasulfate demonstrated prolonged clotting time. Lead compound when intravenously injected in occlusion induced thrombotic rats showed remarkable reduction in the size and weight of the clot at a low dose. Delay in coagulation time was observed by analysing blood plasma isolated from rats preinjected with trehalose octasulfate. A decrease in Adenosine 5′-Diphosphate (ADP) induced platelet aggregation indicated a probable dual anticoagulant and antiplatelet mechanism of action. To summarize, this study presents trehalose octasulfate as a novel, effective, dual acting antithrombotic agent. PMID:25866798

  5. Periprocedural anticoagulation of patients undergoing pericardiocentesis for cardiac tamponade complicating catheter ablation of atrial fibrillation.

    PubMed

    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

    2015-01-01

    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.

  6. Carbon monoxide: Anticoagulant or procoagulant?

    PubMed

    Nielsen, Vance G; Pretorius, Etheresia

    2014-03-01

    Within the past decade there have been several investigations attempting to define the impact of exogenous and endogenous carbon monoxide exposure on hemostasis. Critically, two bodies of literature have emerged, with carbon monoxide mediated platelet inhibition cited as a cause of in vitro human and in vitro/in vivo rodent anticoagulation. In contrast, interaction with heme groups associated with fibrinogen, α₂-antiplasmin and plasmin by carbon monoxide has resulted in enhanced coagulation and decreased fibrinolysis in vitro in human and other species, and in vivo in rabbits. Of interest, the ultrastructure of platelet rich plasma thrombi demonstrates an abnormal increase in fine fiber formation and matting that are obtained from humans exposed to carbon monoxide. Further, thrombi obtained from humans and rabbits have very similar ultrastructures, whereas mice and rats have more fine fibers and matting present. In sum, there may be species specific differences with regard to hemostatic response to carbon monoxide. Carbon monoxide may be a Janus-faced molecule, with potential to attenuate or exacerbate thrombophilic disease.

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

    PubMed Central

    Patel, Raj

    2016-01-01

    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

  8. Severe Extra-Cerebral Anticoagulant-Related Bleeding in Intensive Care Unit

    PubMed Central

    Hauguel, M; Boelle, Py; Pichereau, C; Bourcier, S; Bigé, N; Baudel, JL; Maury, E; Guidet, B; Ait-Oufella, H

    2015-01-01

    Abstract Bleeding is the most frequent complication of anticoagulant therapy, responsible for a number of hospitalizations or deaths. However, studies describing the management and prognosis factors of extra-cerebral anticoagulant-related bleedings in intensive care unit (ICU) are lacking. Retrospective observational study in an 18-bed ICU in a tertiary teaching hospital. From January 2000 to December 2013, all consecutive patients, older than 18 years, admitted for severe anticoagulant-related bleeding (SAB) except intracerebral site were included. A total of 100 patients were included, the mean age was 77 ± 11 years and 62% were women. SAB incidence in ICU doubled over 10 years (P = 0.03). In ICU, the average length of stay was 5 ± 6 days and mortality was 30%. Nonsurviving patients had a higher SAPS II (78 ± 24 vs 53 ± 24, P < 0.0001), a higher SOFA (9.0 ± 3.6 vs 4.7 ± 3.4, P < 0.0001) and received more frequently support therapy such as mechanical ventilation (87% vs 16%, P < 0.0001) and vasopressors (90% vs 27%, P < 0.0001). The volume of blood-derived products transfused was more important in nonsurvivors mainly during the first 24 hours of resuscitation. Rapid anticoagulant reversal therapy was associated with better prognosis (ICU survivors 66% vs 39%, Fisher test P = 0.04). Anterior abdominal wall was identified as a frequent site of bleeding (22%) due to epigastric artery injury during subcutaneous injection of heparin and was associated with a large mortality (55%). Extra-cerebral SAB is a life-threatening complication that requires rapid resuscitation and anticoagulant reversal therapy. Injection of heparin should be done carefully in the subcutaneous tissue thereby avoiding artery injury. PMID:26632750

  9. New aspects on efficient anticoagulation and antiplatelet strategies in sheep

    PubMed Central

    2013-01-01

    Background After addressing fundamental questions in preclinical models in vitro or in small animals in vivo, the translation into large animal models has become a prerequisite before transferring new findings to human medicine. Especially in cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important in vivo model for testing innovative therapies or medical devices prior to clinical application. For a wide variety of sheep model based research projects, an optimal anticoagulation and antiplatelet therapy is mandatory. However, no standardised scheme for this model has been developed so far. Thus the efficacy of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in sheep of different ages. Results Responses to antiplatelet and anticoagulant drugs in different concentrations were studied in the sheep. First, a baseline for the measurement of platelet aggregation was assessed in 20 sheep. The effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite carboxylic acid were detected in every plasma sample. High dose ticagrelor (375 mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep, while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti-factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite receiving quadruple dosages (600 mg bid). Conclusion High dosages of clopidogrel inhibited platelet aggregation merely in a low number of sheep despite sufficient absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for platelet inhibition in

  10. Changing practice of anticoagulation: will target-specific anticoagulants replace warfarin?

    PubMed

    Arepally, Gowthami M; Ortel, Thomas L

    2015-01-01

    The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come. PMID:25587651

  11. Lupus-anticoagulant testing at NOAC trough levels.

    PubMed

    Ratzinger, Franz; Lang, Mona; Belik, Sabine; Jilma-Stohlawetz, Petra; Schmetterer, Klaus G; Haslacher, Helmuth; Perkmann, Thomas; Quehenberger, Peter

    2016-08-01

    Non-vitamin K antagonist oral anticoagulants (NOAC), including rivaroxaban, apixaban or dabigatran, regularly show relevant effects on coagulation tests, making the interpretation of results difficult. The aim of this study was to evaluate possible interferences of NOACs in trough level concentrations in lupus anticoagulant (LA) testing. Citrate plasma specimens of 30 healthy volunteers were spiked with rivaroxaban, apixaban or dabigatran in four plasma concentration levels at or below trough NOAC levels. The NOAC concentration was measured using dedicated surrogate concentration tests and a stepwise diagnostic procedure for LA-testing was applied using screening, mixing and confirmatory testing. Results were compared to NOAC-free specimens. Starting with a plasma concentration of 12.5 ng/ml, dabigatran-spiked specimens showed significant prolongations in the lupus anticoagulant-sensitive activated partial thromboplastin time (aPTT-LA) as well as in the Dilute Russell viper venom time (dRVVT), leading to 43.3 % false positives in confirmatory testing in the dRVVT. In contrast, rivaroxaban, beginning with 7.5 ng/ml, exclusively affected dRVVT-based tests. In confirmatory tests, 30.0 % of rivaroxaban-spiked specimens showed false positive results. Starting with 18.75 ng/ml apixaban, a significant prolongation of the dRVVT and up to 20.7 % false positives in confirmatory tests were found. In contrast to other NOACs tested, apixaban did not present with a dose-dependent increase of the dRVVT ratio. In conclusion, the rate of false positive results in LA-testing is unacceptably high at expected trough levels of NOACs. Even at plasma concentrations below the LLOQ of commercially available surrogate tests, LA testing is best avoided in patients with NOAC therapy.

  12. The new oral anticoagulants: a challenge for hospital formularies.

    PubMed

    Merli, Geno J

    2012-08-01

    Introduction Over the past 60 years, clinicians have used vitamin K antagonists, primarily warfarin, as the sole oral anticoagulants for managing a variety of thrombotic disorders. Warfarin, which requires frequent monitoring, has a variable dose response, a narrow therapeutic index, and numerous drug and dietary interactions. However, intravenous and subcutaneous agents, such as unfractionated heparin, low-molecular-weight heparin, direct thrombin inhibitors, and pentasaccharide, have been introduced over the past 30 years for managing thromboembolic disorders. Recently, 5 new oral anticoagulants, dabigatran, rivaroxaban, apixaban, endoxaban, and betrixaban, have been introduced into clinical trials. Apixaban, rivaroxaban, endoxaban, and betrixaban are specific direct inhibitors of factor Xa, while dabigatran inhibits factor IIa. These drugs have a pharmacological profile that does not require monitoring in order to adjust therapy, which is the mainstay of warfarin management. In addition, these new medications have not shown any major issues regarding food interactions; rather, they demonstrate the potential for limited drug-drug interactions due to their limited metabolism through the cytochrome P450 system. This unique pharmacokinetic profile may provide clinicians with a new era of managing thromboembolic disorders. Two of these agents, dabigatran and rivaroxaban, have been approved by the US Food and Drug Administration (FDA) for stroke prevention in patients with nonvalvular atrial fibrillation (AF); in addition, rivaroxaban can be used in the prevention of venous thromboembolism (VTE) in total hip and knee arthroplasty during the acute and extended periods of risk. However, the challenge for hospital formularies will be the appropriate use and management of these new medications as they become integrated into outpatient care. In order to better understand the issues that pharmacy and therapeutics committees will encounter, a review of the 2 FDA

  13. [Treatment standards of the oral anticoagulant in patients with idiopathic pulmonary embolism].

    PubMed

    Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian

    2016-08-01

    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

  14. [Treatment standards of the oral anticoagulant in patients with idiopathic pulmonary embolism].

    PubMed

    Kowalski, Zbigniew; Kowalski, Piotr; Grzegorek, Damian

    2016-07-01

    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:27590653

  15. Assessing patients’ anticoagulation preferences for the treatment of cancer-associated thrombosis using conjoint methodology

    PubMed Central

    Noble, Simon; Matzdorff, Axel; Maraveyas, Anthony; Holm, Majbrit V.; Pisa, Giovanni

    2015-01-01

    Low molecular weight heparins have demonstrated superiority over coumarins in the extended treatment of cancer-associated thrombosis and are recommended as first-line therapy in clinical guidelines. Non-vitamin K oral antagonists are yet to be evaluated against low molecular weight heparin for this indication. Nevertheless, a perception that patients favor oral anticoagulants over injections may lead to an increased prescribing of warfarin or non-vitamin K oral antagonists despite the evidence gap. There has been no evaluation of cancer patient preferences for anticoagulants and whether such an evidence gap is an acceptable trade-off for patients prescribed orals. We conducted a study to assess what features are most important to CAT patients regarding their choice of anticoagulant. Two modules were applied: Initial in-depth interviews with 9 patients diagnosed with cancer-associated thrombosis, and thereafter quantitative research, where a further 100 patients completed a choice-based-conjoint exercise, where 15 different scenarios were presented to identify the most important attributes of an anticoagulant. Seventy percent of the patients were treated with injected medication (low molecular weight heparin) and 30% with oral medications. Patients most valued an anticoagulant with minimal interference with their cancer treatment (39%), low thrombosis recurrence rate (24%), and low risk of major bleed (19%). Preference for oral administration over injection had moderate importance (13%). The results show that patients prefer an anticoagulant that does not interfere with their cancer treatment, suggesting the primacy of the cancer disease over venous thromboembolism in these patients. Patients also favor efficacy and safety over convenience of route of administration. PMID:26294737

  16. [Anticoagulant rodenticide poisoning in dogs in The Netherlands].

    PubMed

    Robben, J H; Mout, H C; Kuijpers, E A

    1997-09-01

    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

  17. Possible unaware intoxication by anticoagulant rodenticide

    PubMed Central

    Dashti-Khavidaki, Simin; Ghaffari, Saba; Nassiri-Toossi, Mohsen; Amini, Mohsen; Edalatifard, Maryam

    2014-01-01

    Superwarfarin toxicity may be a serious problem. It needs high clinical suspicious in patients with bleeding diathesis without hematologic or liver diseases even in patients with apparent negative history of warfarin or other anticoagulant accessibility. Here we reported a patient with a negative history of any medical diseases or drug administration who was referred with generalized ecchymosis. Increased international normalized ratio and decreased vitamin K-dependent coagulation factors were detected in this patient. His hematologic and liver evaluations were normal. Clinical pharmacist emphasis in taking history revealed using anticoagulant rodenticide all over the farm the patient lived in that might result in unaware intoxication in this patient who suffered dementia. PMID:25535623

  18. Reversal Agents for the Direct Oral Anticoagulants.

    PubMed

    Ansell, Jack E

    2016-10-01

    The vitamin K antagonists (VKAs) are associated with a significant rate of major and fatal bleeding complications. The new direct oral anticoagulants (DOACs), even though having a better bleeding profile than the VKAs, are still associated with serious bleeding. The anticoagulation induced by the VKAs can be reversed with both vitamin K and prothrombin complex concentrates, whereas the DOACs were developed without specific reversal agents. Although there is controversy around the necessity of a reversal agent, most clinicians agree that having a reversal agent for the DOACs would be beneficial. Three reversal agents are currently in development. PMID:27637309

  19. Laboratory determination of old and new targeted anticoagulant agents for prevention of bleeding and thrombotic events in cancer patients.

    PubMed

    Harenberg, Job

    2016-04-01

    A two-fold prolongation of activated partial thromboplastin time (APTT) is established as therapeutic range for therapy with unfractionated heparin, hirudin and argatroban. The international normalized ratio (INR) of 2 to 3 is required to maintain anticoagulation in the therapeutic range of vitamin K antagonists. The therapeutic range of anti-factor Xa activity during therapy with low-molecular weight heparins and danaparoid are less well and of direct oral anticoagulants (DOAC) poorly defined. The relation of aPTT and INR values to thrombotic and bleeding events are well established despite a large variation of values in affected patients. The relation of coagulation values of the other anticoagulants to clinical events is open. The value of determination in cancer patients is higher because of the increased risk for thrombotic and bleeding events of this patient group. Several activities are currently undertaken to certify methods for in vitro diagnostic testing for DAOCs. PMID:27067972

  20. Antiplatelet and anticoagulation agents in acute coronary syndromes: what is the current status and what does the future hold?

    PubMed

    Huber, Kurt; Bates, Eric R; Valgimigli, Marco; Wallentin, Lars; Kristensen, Steen Dalby; Anderson, Jeffrey L; Lopez Sendon, Jose Luis; Tubaro, Marco; Granger, Christopher B; Bode, Christoph; Ohman, Erik Magnus; Steg, Philippe Gabriel

    2014-11-01

    Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio. PMID:25440788

  1. Anticoagulation in patients with impaired renal function and with haemodialysis. Anticoagulant effects, efficacy, safety, therapeutic options.

    PubMed

    Harenberg, J; Hentschel, V A-T; Du, S; Zolfaghari, S; Krämer, R; Weiss, C; Krämer, B K; Wehling, M

    2015-01-01

    Patients with impaired renal function are exposed to an increased risk for bleeding complications depending on the amount of the anticoagulant eliminated by the kidneys. The elimination of unfractionated heparins, vitamin K antagonists and argatroban is only minimally influenced by a reduced renal function. Low-molecular weight heparins, fondaparinux, danaparoid, hirudins and non-vitamin K antagonist oral anticoagulants (NOAC) cause a variably increased bleeding risk in renal impairment. Dose reductions are recommended for all of these anticoagulants in renal impairment, some are even contraindicated at certain levels of renal impairment. Their benefit over the conventional anticoagulants is preserved if renal dosing is employed. For end-stage renal disease patients specific treatment regimens are required. PMID:25405246

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

    PubMed

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

    2014-10-01

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

  3. Non-traumatic compartment syndrome secondary to deep vein thrombosis and anticoagulation

    PubMed Central

    Newman, Peter Alexander; Deo, Sunny

    2014-01-01

    We describe an unusual case of non-traumatic compartment syndrome in three compartments of the left lower limb in a 57-year-old male inpatient. He had recently been started on anticoagulation therapy for multiple pulmonary emboli and deep vein thrombosis of the left posterior tibial and peroneal veins. Three of the four osteofascial compartments had pressures above 70 mm Hg, hence four compartment fasciotomies were performed. Postoperatively, intravenous heparin therapy was started resulting in a significant blood loss, but he had no neurovascular deficit. At reoperation, for primary wound closure, his tissues looked healthy. Non-traumatic causes of acute compartment syndrome, including deep venous thrombosis and anticoagulation, are considered. PMID:24443334

  4. Cerebrovascular Accident due to Thyroid Storm: Should We Anticoagulate?

    PubMed Central

    Gonzalez-Rivera, Alexis; Coste-Sibilia, Santiago

    2016-01-01

    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. PMID:27597905

  5. Cerebrovascular Accident due to Thyroid Storm: Should We Anticoagulate?

    PubMed

    Gonzalez-Bossolo, Alex; Gonzalez-Rivera, Alexis; Coste-Sibilia, Santiago

    2016-01-01

    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.

  6. New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness

    PubMed Central

    Mani, Helen; Lindhoff-Last, Edelgard

    2014-01-01

    Atrial fibrillation (AF) continues to be a leading cause of cerebrovascular morbidity and mortality resulting from cardioembolic stroke. Oral anticoagulation therapy has been shown to decrease the incidence of cardioembolic stroke in patients with AF by more than 50%. Appropriate use of anticoagulation with vitamin K antagonists requires precise adherence and monitoring. A number of factors that potentially induce patients’ dissatisfaction reduce quality of patient life. New direct oral anticoagulants, such as the direct factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and the thrombin inhibitor dabigatran, were developed to overcome the limitations of the conventional anticoagulant drugs. However, models to optimize the benefit of therapy and to ensure that therapy can be safely continued are missing for the new oral anticoagulants. This review will briefly describe the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban with focus on their use for prevention of embolic events in AF. Moreover, it will discuss the safety, efficacy, cost data, and benefit for patients’ quality of life and adherence. PMID:24970997

  7. Antithrombotic Therapy for Atrial Fibrillation

    PubMed Central

    You, John J.; Singer, Daniel E.; Howard, Patricia A.; Lane, Deirdre A.; Eckman, Mark H.; Fang, Margaret C.; Hylek, Elaine M.; Schulman, Sam; Go, Alan S.; Hughes, Michael; Spencer, Frederick A.; Manning, Warren J.; Halperin, Jonathan L.

    2012-01-01

    Background: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized

  8. Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?

    PubMed Central

    Violi, Francesco; Lip, Gregory YH; Pignatelli, Pasquale; Pastori, Daniele

    2016-01-01

    Abstract Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables. The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs. Data sources are MEDLINE via PubMed and Cochrane database. All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone. We performed a systematic review of the literature up to October 2015, searching for a combination of “food,” “diet,” “vitamin K,” “phylloquinone,” “warfarin,” “INR,” “coagulation,” and “anticoagulant.” Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day). Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable. The available evidence does not support current advice to modify

  9. Updates in the perioperative and emergency management of non-vitamin K antagonist oral anticoagulants.

    PubMed

    Faraoni, David; Levy, Jerrold H; Albaladejo, Pierre; Samama, Charles-Marc

    2015-01-01

    Perioperative management of patients treated with the non-vitamin K antagonist oral anticoagulants is an ongoing challenge. Due to the lack of good clinical studies involving adequate monitoring and reversal therapies, management requires knowledge and understanding of pharmacokinetics, renal function, drug interactions, and evaluation of the surgical bleeding risk. Consideration of the benefit of reversal of anticoagulation is important and, for some low risk bleeding procedures, it may be in the patient's interest to continue anticoagulation. In case of major intra-operative bleeding in patients likely to have therapeutic or supra-therapeutic levels of anticoagulation, specific reversal agents/antidotes would be of value but are currently lacking. As a consequence, a multimodal approach should be taken which includes the administration of 25 to 50 U/kg 4-factor prothrombin complex concentrates or 30 to 50 U/kg activated prothrombin complex concentrate (FEIBA®) in some life-threatening situations. Finally, further studies are needed to clarify the ideal therapeutic intervention. PMID:25925382

  10. Minimizing bleeding risk in patients receiving direct oral anticoagulants for stroke prevention

    PubMed Central

    Habert, Jeffrey Steven

    2016-01-01

    Many primary care physicians are wary about using direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (AF). Factors such as comorbidities, concomitant medications, and alcohol misuse increase concerns over bleeding risk, especially in elderly and frail patients with AF. This article discusses strategies to minimize the risk of major bleeding events in patients with AF who may benefit from oral anticoagulant therapy for stroke prevention. The potential benefits of the DOACs compared with vitamin K antagonists, in terms of a lower risk of intracranial hemorrhage, are discussed, together with the identification of reversible risk factors for bleeding and correct dose selection of the DOACs based on a patient’s characteristics and concomitant medications. Current bleeding management strategies, including the new reversal agents for the DOACs and the prevention of bleeding during preoperative anticoagulation treatment, in addition to health care resource use associated with anticoagulation treatment and bleeding, are also discussed. Implementing a structured approach at an individual patient level will minimize the overall risk of bleeding and should increase physician confidence in using the DOACs for stroke prevention in their patients with nonvalvular AF. PMID:27785089

  11. Transcatheter Arterial Embolization of Concurrent Spontaneous Hematomas of the Rectus Sheath and Psoas Muscle in Patients Undergoing Anticoagulation

    SciTech Connect

    Basile, Antonio; Medina, Jose Garcia; Mundo, Elena; Medina, Vicente Garcia; Leal, Rafael

    2004-11-15

    We report a case of concurrent rectus sheath and psoas hematomas in a patient undergoing anticoagulant therapy, treated by transcatheter arterial embolization (TAE) of inferior epigastric and lumbar arteries. Computed tomography (CT) demonstrated signs of active bleeding in two hematomas of the anterior and posterior abdominal walls. Transfemoral arteriogram confirmed the extravasation of contrast from the right inferior epigastric artery (RIEA). Indirect signs of bleeding were also found in a right lumbar artery (RLA). We successfully performed TAE of the feeding arteries. There have been few reports in the literature of such spontaneous hemorrhages in patients undergoing anticoagulation, successfully treated by TAE.

  12. A comparison of rural and urban anticoagulation management of atrial fibrillation in a southwest Missouri health system.

    PubMed

    Hover, Alexander R; Rogers, James T; Hunt, Carla

    2003-01-01

    The purpose of this study is to determine if an opportunity exists to improve anticoagulation therapy for non-hospitalized, chronic atrial fibrillation patients cared for by St. John's Health System physicians. Clinical chart review consisted of 200 patients in both the urban and rural practice groups. Urban practices were found to have 95 percent of the cases receiving warfarin, 95 percent confidence interval (90-100). Rural practices were found to have 97 percent of the cases anticoagulated, 95 percent confidence interval (88-99).

  13. Utilization of Oral Anticoagulation in a Teaching Hospital in Nigeria

    PubMed Central

    Anakwue, RC; Ocheni, S; Madu, AJ

    2014-01-01

    Background: Anticoagulation is an essential lifesaving management practice indicated for arterial, venous and intracardiac thromboembolism. Aim: This study was undertaken to examine the utilization of anticoagulation services in University of Nigeria Teaching Hospital, Enugu (UNTH) Nigeria. Materials and Methods: This retrospective study involved assessing data from folders of subjects on anticoagulation and monitoring in UNTH, Enugu. Patients’ profile, risk factors, diagnosis, indication for oral anticoagulation, anticoagulant used; target, monitoring, outcome and complications of anticoagulation were recorded. Results: A total of 26 patients over a period of 5 years were on anticoagulation and laboratory monitoring done in UNTH. The mean age of the patients was 53.4 years and more females than males were on anticoagulation and monitoring (F14:M12). The most common indications for anticoagulation include deep venous thrombosis/pulmonary embolism, congestive heart failure with atrial fibrillation and mitral valve disease with atrial fibrillation. Desired clinical outcome was achieved in eight patients 8/26 (30.8%). Minor bleeding was the only complication reported in three patients 3/26 (11.5%). Conclusion: The absence of diagnostic tools and anticoagulation monitoring clinics and the apprehension of adverse effects have combined to make this lifesaving treatment inaccessible to many patients in Nigeria. PMID:25364603

  14. [Therapeutic equivalence of the new oral anticoagulants].

    PubMed

    Moreno Villar, A; Nacle López, I; Barbero Hernández, M J; Lizan Tudela, L

    2015-10-01

    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

  15. [Anticoagulation in patients with chronic renal failure].

    PubMed

    Niksic, L; Saudan, P; Boehlen, F

    2006-03-01

    Anticoagulation may be difficult to implement in patients suffering from chronic renal failure on account of platelet disorders and impaired clearance of some anticoagulant drugs. Although no adjustment of heparin and coumarin dosage is necessary, more frequent testing of coagulation pathways may be required when these drugs are used in patients with renal failure. Long-term use of LMWH should be implemented cautiously with regular testing of anti-factor Xa activity and a half-dose may be advocated in patients with a creatinine clearance < 30 ml/mn. Danaparoid and thrombin inhibitors should be used mainly in patients suffering from renal failure and heparin-induced thrombocytopenia with regular monitoring of coagulation tests. PMID:16562602

  16. Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants.

    PubMed

    Hillis, Christopher M; Crowther, Mark A

    2015-06-01

    The acute phase of venous thromboembolism (VTE) treatment focuses on the prompt and safe initiation of full-dose anticoagulation to decrease morbidity and mortality. Immediate management consists of resuscitation, supportive care, and thrombolysis for patients with haemodynamically significant pulmonary embolism (PE) or limb-threatening deep-vein thrombosis (DVT). Patients with contraindications to anticoagulants are considered for vena cava filters. Disposition for the acute treatment of VTE is then considered based on published risk scores and the patient's social status, as the first seven days carries the highest risk for VTE recurrence, extension and bleeding due to anticoagulation. Next, a review of: immediate and long-term bleeding risk, comorbidities (i. e. active cancer, renal failure, obesity, thrombophilia), medications, patient preference, VTE location and potential for pregnancy should be undertaken. This will help determine the most suitable anticoagulant for immediate treatment. The non-vitamin K antagonist oral anticoagulants (NOACs), including the factor Xa inhibitors apixaban, edoxaban and rivaroxaban as well as the direct-thrombin inhibitor dabigatran, are increasing the convenience of and options available for VTE treatment. Current options for immediate treatment include low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), fondaparinux, apixaban, or rivaroxaban. LMWH or UFH may be continued as monotherapy or transitioned to treatment with a VKA, dabigatran or edoxaban. This review describes the upfront treatment of VTE and the evolving role of NOACs in the contemporary management of VTE.

  17. EDUC’AVK: Reduction of Oral Anticoagulant-related Adverse Events After Patient Education: A Prospective Multicenter Open Randomized Study

    PubMed Central

    Labarère, José; Yver, Jacqueline; Satger, Bernadette; Allenet, Benoit; Berremili, Touffek; Fontaine, Michèle; Franco, Guy; Bosson, Jean Luc

    2008-01-01

    Background Long-term oral anticoagulation treatment is associated with potential morbidity. Insufficient patient education is linked to poorly controlled anticoagulation. However the impact of a specific educational program on anticoagulation related morbidity remains unknown. Objective To evaluate the effect of an oral anticoagulation patient education program in reducing both hemorrhagic and recurrent thrombotic complications. Design/Participants We conducted a prospective, multicenter open randomized study, comparing an interventional group who received a specific oral anticoagulation treatment educational program with a control group. Eligible patients were older than 18 and diagnosed as having deep vein thrombosis or pulmonary embolism requiring therapy with a vitamin K antagonist for 3 months or more. Our primary outcome was the occurrence of hemorrhagic or thromboembolic events. Results During the 3-month follow-up the main outcome criteria were observed 20 times (6.6% of patients), 5 (3.1%) in the experimental and 15 (10.6%) in the control group. Consequently, in multivariate analysis, the cumulative risk reduction in the experimental group was statistically significant (OR 0.25, 95% CI 0.1 – 0.7,  < 0.01). Conclusions Patient education using an educational program reduced VKA-related adverse event rates. PMID:18566863

  18. Approach to the new oral anticoagulants in family practice

    PubMed Central

    Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

    2014-01-01

    Abstract Objective To compare key features of the new oral anticoagulants (NOACs)—dabigatran, rivaroxaban, and apixaban—and to address questions that arise when comparing the NOACs. Sources of information PubMed was searched for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation (AF) and for the treatment of acute venous thromboembolism (VTE). Main message All NOACs are at least as effective as warfarin for stroke prevention in patients with nonvalvular AF, and are at least as safe in terms of bleeding risk according to 3 large trials. Meta-analyses of these trials have shown that, compared with warfarin therapy, NOACs reduced total mortality, cardiovascular mortality, and intracranial bleeding, and there was a trend toward less overall bleeding. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring, and few known or defined drug or food interactions. Potential drawbacks of NOACs include a risk of bleeding that might be increased in patients older than 75 years, increased major gastrointestinal bleeding with high-dose dabigatran, increased dyspepsia with dabigatran, the lack of a routine laboratory test to reliably measure anticoagulant effect, and the lack of an antidote for reversal. No direct comparisons of NOACs have been made in randomized controlled trials, and the choice of NOAC is influenced by individual patient characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity (eg, renal dysfunction). Conclusion The NOACs represent important alternatives in the management of patients with AF and VTE, especially for patients who have difficulty accessing regular coagulation monitoring. The companion to this article addresses common “what if” questions that arise in the long-term clinical follow-up and management of patients receiving NOACs. PMID:25392438

  19. Personalizing oral anticoagulant treatment in patients with atrial fibrillation.

    PubMed

    Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado

    2013-08-01

    For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection. PMID:23957907

  20. Personalizing oral anticoagulant treatment in patients with atrial fibrillation.

    PubMed

    Capranzano, Piera; Miccichè, Eligio; D'Urso, Lucia; Privitera, Fiorella; Tamburino, Corrado

    2013-08-01

    For decades, warfarin has remained the standard oral anticoagulation for stroke prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs) have been recently approved for stroke prevention in non-valvular AF: dabigatran, rivaroxaban and apixaban. Better pharmacological and clinical profiles make these newcomers a preferable alternative over warfarin. Current AF guidelines do not endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the anticoagulation regimen should be personalized based on the relative efficacy and safety of different agents across subgroups stratified by thrombotic and bleeding risk, as well as on other clinical factors, including anticoagulation control on warfarin, drug interactions, compliance and need for coagulation monitoring. This review appraises i) the randomized evidence on approved NOACs versus warfarin in AF across subgroups stratified by risk factors of stroke and bleeding and by the anticoagulation level reached on warfarin; and ii) clinical factors impacting on the anticoagulation regimen selection.

  1. Safety and Efficacy Outcomes of Home and Hospital Warfarin Management Within a Pediatric Anticoagulation Clinic.

    PubMed

    Jones, Sophie; McLoughlin, Siobhan; Piovesan, Dana; Savoia, Helen; Monagle, Paul; Newall, Fiona

    2016-04-01

    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.

  2. Plasma superwarfarin levels and vitamin K1 treatment in dogs with anticoagulant rodenticide poisoning.

    PubMed

    Robben, J H; Kuijpers, E A; Mout, H C

    1998-01-01

    The plasma concentration, plasma half-life (t1/2), and mean residence time (MRT) of rodenticide anticoagulants were determined in 21 dogs in which a preliminary diagnosis of anticoagulant rodenticide poisoning had been made. Brodifacoum, difethialone, and difenacoum were detected by high-performance liquid chromatography (HPLC) in the plasma of 13, 3, and 2 dogs, respectively. At presentation the plasma concentration ranged from below the detection limit (10 ng/L) to 851 ng/L. Toxin could not be detected in 3 dogs, despite these animals showing characteristic coagulation disturbances and a positive response to therapy with vitamin K1. In 7 dogs the estimated t1/2 of brodifacoum ranged from 0.9 to 4.7 (median 2.4) days with a MRT of 1.9 to 3.7 (median 2.8) days. In 2 dogs the individual t1/2 of difethialone was 2.2 and 3.2 days and the MRT was 2.3 and 2.8 days, respectively. Two dogs died during emergency treatment. Treatment in the remaining 19 dogs consisted of the administration of vitamin K1 and supportive therapy. The dose of vitamin K1 was reduced in a stepwise manner as long as the prothrombin time remained within physiological limits. The variation in initial plasma concentrations of the anticoagulants combined with the results of treatment support the idea that an individual therapeutic approach is warranted. PMID:9477532

  3. Symptomatic Patients with Intraluminal Carotid Thrombus: Outcome with a Strategy of Initial Anticoagulation

    PubMed Central

    Vellimana, Ananth K.; Kadkhodayan, Yasha; Rich, Keith M.; Cross, Dewitte T.; Moran, Christopher J.; Zazulia, Allyson R.; Lee, Jin-Moo; Chicoine, Michael R.; Dacey, Ralph G.; Derdeyn, Colin P.; Zipfel, Gregory J.

    2013-01-01

    Background Optimal treatment for patients with symptomatic intraluminal carotid thrombus (ICT) remains poorly defined. Methods We performed a retrospective chart review of patients presenting to our institution between 2001 and 2011 with symptomatic ICT. Results Twenty-four patients (16 males, 8 females) with ICT presented with ischemic stroke (n=18) or TIA (n=6). All were treated initially with anticoagulation ± antiplatelet drugs. Eight of these patients had no or mild carotid stenosis on initial angiography and were treated with medical management alone. The remaining 16 patients had moderate or severe carotid stenosis on initial angiography. Of these, 10 underwent delayed revascularization (endarterectomy, n=8; angioplasty and stenting, n=2), 2 refused revascularization, and 4 were treated with medical therapy alone. One patient had multiple TIAs despite medical therapy and eventually underwent CEA; the remaining 23 patients had no TIAs. No patient suffered ischemic or hemorrhagic stroke while on anticoagulation, during the perioperative period or in long-term follow up; one patient died of an unrelated condition (mean follow-up = 16.4 months). Conclusion Our results suggest that initial anticoagulation of symptomatic ICT results in a low rate of recurrent ischemic events and that carotid revascularization, if indicated, can be safely performed in a delayed manner. PMID:23061393

  4. Anticoagulation and population risk of stroke and death in incident atrial fibrillation: a population-based cohort study

    PubMed Central

    Yu, Amy Y.X.; Malo, Shaun; Wilton, Stephen; Parkash, Ratika; Svenson, Lawrence W.; Hill, Michael D.

    2016-01-01

    Background: Atrial fibrillation increases the risk of stroke and death. Anticoagulation therapy is an effective treatment for stroke prevention, but remains underused in the community. We sought to determine the effectiveness and safety of anticoagulation therapy in an inception cohort with new-onset atrial fibrillation in the province of Alberta, Canada. Methods: We conducted a population-based cohort study of atrial fibrillation using an administrative database from Alberta's publicly funded and universally available health care system. All new-onset atrial fibrillation patients from Jan. 1, 2009, to Dec. 31, 2010, were included in the cohort and followed through Dec. 31, 2013. We assessed anticoagulation status as a predictor of stroke and death using time-to-event analysis and adjusted for sex and CHADS2 (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke or transient ischemic attack) score using Cox proportional hazards modelling. Results: We identified 10 745 patients, 7358 (68.5%) of whom received anticoagulation therapy, principally with warfarin (n = 6997, 95.1%). Anticoagulation therapy was associated with significantly decreased risk of ischemic stroke (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), all stroke (HR 0.77, 95% CI 0.65-0.91), all stroke and death (HR 0.70, 95% CI 0.62-0.72) and all-cause mortality (HR 0.67, 95% CI 0.62-0.72), despite an association with increased risk of hemorrhagic stroke (HR 1.92, 95% CI 1.17-3.16). There was a neutral association with subdural (HR 1.01, 95% CI 0.53-1.93) and gastrointestinal (HR 0.96, 95% CI 0.70-1.31) hemorrhage. Interpretation: Anticoagulation therapy is effective and safe for stroke prevention and decreases mortality in patients with incident atrial fibrillation. These population data support an aggressive approach to screening for atrial fibrillation and treatment with anticoagulant medicines to prevent stroke and death. PMID:27280108

  5. Anticoagulation for the Acute Management of Ischemic Stroke

    PubMed Central

    Robinson, Austin A.; Ikuta, Kevin; Soverow, Jonathan

    2014-01-01

    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 circumstances while showing its potential in others. PMID:24910565

  6. Embolic Stroke in Cardiomyopathy: Should Patients be Anticoagulated?

    PubMed

    Narang, Akhil; Lang, Roberto M

    2016-05-01

    Despite advances in the treatment of patients with heart failure, mortality is still substantial. Part of this mortality is explained by cardioembolic stroke. Patients with heart failure are predisposed to developing cardioembolic strokes owing to abnormalities in Virchow's triad (endothelial function, relative hypercoagulable state, and static blood flow). Several randomized controlled trials have addressed whether patients with heart failure benefit from anticoagulation. Overall, the results suggest the risk of bleeding with anticoagulation outweighs any small benefit conferred by anticoagulation. PMID:27150169

  7. [Recommendations on use of direct oral anticoagulants in the perioperative period].

    PubMed

    Llau, Juan V; Ferrandis, Raquel; Castillo, Jorge; de Andrés, José; Gomar, Carmen; Gómez-Luque, Aurelio; Hidalgo, Francisco; Torres, Luis M

    2012-10-01

    Because of the characteristics of direct oral anticoagulants (DOA), the lack of an antidote to completely reverse their anticoagulant effects, the absence of standardization in monitoring of their effects, and limited experience of their use, specific recommendations for their management in the perioperative period or in emergencies are required. In elective surgery, in patients with normal renal function and low hemorrhagic/ thrombotic risk, DOA should be withdrawn 2 days before the intervention; when the hemorrhagic/ thrombotic risk is higher, bridge therapy with a low molecular weight hepatin beginning 5 days before the intervention is proposed as an alternative. In emergency surgery, systematic administration of hemostatic drugs as prophylaxis is not recommended. In DOA-related acute hemorrhage, administration of prothrombin complex concentrate, fresh plasma or factor VIIa should be evaluated, and general measures to control bleeding should be implemented.

  8. Interpretation of coagulation test results under direct oral anticoagulants.

    PubMed

    Mani, H

    2014-06-01

    Diagnostic of global coagulation parameters is part of the daily clinical routine practice in conservative as well in operative disciplines. The correct interpretation of in vitro test results in context to the ex vivo influence of anticoagulant drugs and the in vivo hemostatic system of the individual patient is dependent on the doctors clinical and laboratory experience. This article shortly reviews the laboratory interference of oral anticoagulants including the target-specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation parameters and discusses the potential of several methods for measuring the anticoagulant effect of the direct oral anticoagulants.

  9. Laboratory Measurement of the Anticoagulant Activity of the Target-specific Oral Anticoagulant Agents: A Systematic Review

    PubMed Central

    Cuker, Adam; Siegal, Deborah M.; Crowther, Mark A.; Garcia, David A.

    2014-01-01

    Background The target-specific oral anticoagulant agents (TSOACs) do not require routine laboratory monitoring. However, laboratory measurement may be desirable in special situations and populations. Objectives This study’s objective is to systematically review and summarize current evidence regarding laboratory measurement of the anticoagulant activity of dabigatran, rivaroxaban, and apixaban. Methods We searched PubMed and Web of Science for studies that reported a relationship between drug levels of dabigatran, rivaroxaban, and apixaban and coagulation assay results. Study quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Results We identified 17 eligible studies for dabigatran, 15 for rivaroxaban, and 4 for apixaban. For dabigatran, a normal thrombin time excludes clinically relevant drug concentrations. The activated partial thromboplastin time (APTT) and prothrombin time (PT) are less sensitive and may be normal at trough drug levels. The dilute thrombin time (R2 0.92–0.99) and ecarin-based assays (R2 0.92–1.00) show excellent linearity across on-therapy drug concentrations and may be used for drug quantification. In terms of rivaroxaban and apixaban, anti-Xa activity is linear (R2 0.89–1.00) over a wide range of drug levels and may be used for drug quantification. Undetectable anti-Xa activity likely excludes clinically relevant drug concentrations. The PT is less sensitive (especially for apixaban); a normal PT may not exclude clinically relevant levels. The APTT demonstrates insufficient sensitivity and linearity for quantification. Conclusions Dabigatran, rivaroxaban, and apixaban exhibit variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in TSOAC-treated patients. More information on the relationship between drug levels and clinical outcomes is needed. PMID:25212648

  10. Cost of vitamin K antagonist anticoagulant treatment in patients with metallic prosthetic valve in mitral position

    PubMed Central

    Ene, Gabriela; Garcia Raso, Aránzazu; Gonzalez-Dominguez Weber, Almudena; Hidalgo-Vega, Álvaro; Llamas, Pilar

    2016-01-01

    Background: The initiation of oral anticoagulation therapy after valve replacement surgery requires strict monitoring because these patients are at high risk for the development of thrombotic complications and present an increased risk of bleeding. Objectives: The aim of this study was to examine the total healthcare costs of oral anticoagulant treatment with vitamin K antagonists in patients with metallic prosthetic valves in the mitral position. Methods: Data from clinical records were used in the study including international normalized ratio results, number of medical visits, type of anticoagulant, use of rescue medication and hospital admissions from related complications. The drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included in the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the diagnosis-related group price for each case. Results: We collected data from 151 patients receiving oral anticoagulation therapy with vitamin K antagonist who were diagnosed with mitral prosthesis (n = 90), mitro-aortic prosthesis (n = 57), and mitral and tricuspid prosthesis (n = 4). The total direct healthcare cost was €15302.59, with a mean total cost per patient per year of €1558.15 (±2774.58) consisting of 44.38 (±42.30) for drug cost, €71.41 (±21.43) for international normalized ratio monitoring, €429.52 (±126.87) for medical visits, €26.31 (±28.38) for rescue medication and €986.53 (±2735.68) for related complications. Conclusion: Most direct healthcare costs associated with the sampled patients arose from the specialist-care monitoring required for treatment. Good monitoring is inversely related to direct healthcare costs. PMID:27579168

  11. Balancing ischaemia and bleeding risks with novel oral anticoagulants.

    PubMed

    Baber, Usman; Mastoris, Ioannis; Mehran, Roxana

    2014-12-01

    Vitamin K antagonists (VKAs) have long been the standard of care for treatment of venous thromboembolism (VTE), and thromboprophylaxis in atrial fibrillation (AF). Despite their efficacy, their use requires frequent monitoring and is complicated by drug-drug interactions and the need to maintain a narrow therapeutic window. Since 2009, novel oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban, have become alternative options to VKAs owing to their predictable and safe pharmacological profiles. The overall clinical effect of these drugs, which is a balance between ischaemic benefit and bleeding harm, varies according to the clinical scenario. As adjunctive therapy to dual antiplatelet therapy in patients with acute coronary syndrome, NOACs are associated with incremental bleeding risks and modest benefits. For treatment of VTE, NOACs have a safer profile than VKAs and a similar efficacy. In thromboprophylaxis in AF, NOACs are associated with the greatest benefits by reducing both ischaemic events and haemorrhagic complications and might reduce mortality compared with VKAs. The role of NOACs continues to evolve as these drugs are evaluated in different patient populations, including those with renal impairment or with AF and undergoing percutaneous coronary intervention. PMID:25367652

  12. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands.

    PubMed

    Ten Cate, V; Ten Cate, H; Verheugt, F W A

    2016-10-01

    There are over 385,000 cases of atrial fibrillation (AF) in the Netherlands, with over 45,000 new cases each year. Among other things, AF patients are at high risk of stroke. Patients are often prescribed oral anticoagulation, such as vitamin K antagonists (VKA), to mitigate these risks. A recently introduced class of oral anticoagulants, non-vitamin K antagonists (NOAC), is quickly gaining currency in global clinical practice. This study provides insight into the changes these new drugs will bring about in Dutch clinical practice.GARFIELD-AF is a large-scale observational AF patient registry initiated in 2009 to track the evolution of global anticoagulation practice, and to study the impact of NOAC therapy in AF in particular. The registry includes a wide array of baseline characteristics and has a particular focus on: (1) bleeding and thromboembolic events; (2) international normalised ratio fluctuations; and (3) therapy compliance and persistence patterns. The results in this paper provide the baseline characteristics of the first cohorts of Dutch participants in this registry and discuss some of the consequences of the changes in anticoagulation practice.Although VKA therapy remains overwhelmingly favoured by Dutch practitioners, NOACs are clearly gaining in popularity. Between 2011 and 2014, NOACs constituted an increasingly large proportion of prescriptions for oral anticoagulants.The insights provided by the GARFIELD-AF registry can be used by healthcare systems to inform better budgetary strategies, by practitioners to better tailor treatment pathways to patients, and finally to promote awareness of the various available treatment options and their associated risks and benefits for patients. PMID:27561277

  13. The role of anticoagulation clinics in the era of new oral anticoagulants.

    PubMed

    Testa, Sophie; Paoletti, Oriana; Zimmermann, Anke; Bassi, Laura; Zambelli, Silvia; Cancellieri, Emilia

    2012-01-01

    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.

  14. Real-world characteristics of hospitalized frail elderly patients with atrial fibrillation: can we improve the current prescription of anticoagulants?

    PubMed Central

    Annoni, Giorgio; Mazzola, Paolo

    2016-01-01

    Background In elderly patients, especially those older than 80 years, atrial fibrillation (AF) is associated with an almost 25% increased risk of stroke. Stroke prophylaxis with anticoagulants is therefore highly recommended. The prevalence of factors that have been associated with a lower rate of prescription and adherence to anticoagulant therapy in these patients is little known. The objective of this study was to explore the clinical characteristics of elderly subjects, with and without AF, consecutively admitted to an acute geriatric unit, discussing factors that may decrease the persistence on stroke prophylaxis therapy. We also highlight possible strategies to overcome the barriers conditioning the current underuse of oral anticoagulants in this segment of the population. Methods A retrospective observational study was performed on a cohort of elderly patients with and without AF admitted to the Acute Geriatric Unit of San Gerardo Hospital (Monza, Italy). Results Compared to patients without AF (n = 1216), those with AF (n = 403) had a higher Charlson Comorbidity Index (3 vs. 2, P < 0.001), number of administered drugs (4 vs. 3, P < 0.001), rate of heart failure (36.5% vs. 12%, P < 0.001) and chronic kidney disease (20.6 vs. 13.2, P < 0.001). Many patients with AF were frail (54%) or pre-frail (29%). Conclusions Elderly patients with AF have higher rates of conditions that affect adherence to traditional anticoagulant therapy (vitamin K antagonists, VKA). New direct oral anticoagulants (DOAs) can help overcome this problem. In order to prescribe the most appropriate VKA or DOAs, with the best efficacy/safety profile and the highest compliance, a comprehensive geriatric assessment should always accompany the scores for thrombotic and hemorrhagic risk stratification. PMID:27103917

  15. New anticoagulants: pharmacology and clinical studies.

    PubMed

    Samama, Charles Marc

    2011-02-01

    The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard. PMID:21404139

  16. Shortfalls using second-generation anticoagulant rodenticides.

    PubMed

    Borst, G H A; Counotte, G H M

    2002-03-01

    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

  17. New anticoagulants: pharmacology and clinical studies.

    PubMed

    Samama, Charles Marc

    2011-02-01

    The marketing of new anticoagulant drugs has led us to review the development of rivaroxaban and apixaban (oral anti-Xa drugs) and dabigatran (an oral thrombin inhibitor). The results are different in terms of efficacy and tolerance. Each molecule has its own field of application but it is not at all certain that each will find its place. Though the results are favourable for these orally active drugs in the orthopaedic setting, it is clear that only cardiological applications will give a final green light for these products. The future will be fascinating in this regard.

  18. Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012.

    PubMed

    Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B

    2014-09-01

    Approximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives. PMID:25173533

  19. MRI Screening for Chronic Anticoagulation in Atrial Fibrillation

    PubMed Central

    Fisher, Mark

    2013-01-01

    Anticoagulation is highly effective in preventing stroke due to atrial fibrillation, but numerous studies have demonstrated low utilization of anticoagulation for these patients. Assessment of clinicians’ attitudes on this topic indicate that fear of intracerebral hemorrhage (ICH), rather than appreciation of anticoagulation benefits, largely drives clinical decision-making for treatment with anticoagulation in atrial fibrillation. Risk stratification strategies have been used for anticoagulation benefits and hemorrhage risk, but ICH is not specifically addressed in the commonly used hemorrhage risk stratification systems. Cerebral microbleeds are cerebral microscopic hemorrhages demonstrable by brain MRI, indicative of prior microhemorrhages, and predictive of future risk of ICH. Prevalence of cerebral microbleeds increases with age; and cross-sectional and limited prospective studies generally indicate that microbleeds confer substantial risk of ICH in patients treated with chronic anticoagulation. MRI thus is a readily available and appealing modality that can directly assess risk of future ICH in patients receiving anticoagulants for atrial fibrillation. Incorporation of MRI into routine practice is, however, fraught with difficulties, including the uncertain relationship between number and location of microbleeds and ICH risk, as well as cost-effectiveness of MRI. A proposed algorithm is provided, and relevant advantages and disadvantages are discussed. At present, MRI screening appears most appropriate for a subset of atrial fibrillation patients, such as those with intermediate stroke risk, and may provide reassurance for clinicians whose concerns for ICH tend to outweigh benefits of anticoagulation. PMID:24109470

  20. Avoiding Medication Errors: Reducing Harm in Residents Using Oral Anticoagulants.

    PubMed

    Grissinger, Matthew; Gaunt, Michael J; Rich, Darryl S

    2016-01-01

    Medication errors involving oral anticoagulants have led to serious adverse events, including hemorrhage, treatment failures leading to thromboembolic events, and death. This article will highlight medication errors that may arise during the use of oral anticoagulants and provide risk-reduction strategies to address the potential for error and patient harm. PMID:27250070

  1. Novel oral anticoagulants for stroke prevention in atrial fibrillation: focus on apixaban.

    PubMed

    Potpara, Tatjana S; Polovina, Marija M; Licina, Marina M; Stojanovic, Radan M; Prostran, Milica S; Lip, Gregory Y H

    2012-06-01

    Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality

  2. Rationale and design of the Clarification of Optimal Anticoagulation through Genetics trial

    PubMed Central

    Kimmel, Stephen E.; French, Benjamin; Anderson, Jeffrey L.; Gage, Brian F.; Johnson, Julie A.; Rosenberg, Yves D.; Geller, Nancy L.; Kasner, Scott E.; Eby, Charles S.; Joo, Jungnam; Caldwell, Michael D.; Goldhaber, Samuel Z.; Hart, Robert G.; Cifelli, Denise; Madigan, Rosemary; Brensinger, Colleen M.; Goldberg, Suzanne; Califf, Robert M.; Ellenberg, Jonas H.

    2014-01-01

    Background Current dosing practices for warfarin are empiric and result in the need for frequent dose changes as the international normalized ratio gets too high or too low. As a result, patients are put at increased risk for thromboembolism, bleeding, and premature discontinuation of anticoagulation therapy. Prior research has identified clinical and genetic factors that can alter warfarin dose requirements, but few randomized clinical trials have examined the utility of using clinical and genetic information to improve anticoagulation control or clinical outcomes among a large, diverse group of patients initiating warfarin. Methods The COAG trial is a multicenter, double-blind, randomized trial comparing 2 approaches to guiding warfarin therapy initiation: initiation of warfarin therapy based on algorithms using clinical information plus an individual's genotype using genes known to influence warfarin response (“genotype-guided dosing”) versus only clinical information (“clinical-guided dosing”) (www.clinicaltrials.gov Identifier: NCT00839657). Results The COAG trial design is described. The study hypothesis is that, among 1,022 enrolled patients, genotype-guided dosing relative to clinical-guided dosing during the initial dosing period will increase the percentage of time that patients spend in the therapeutic international normalized ratio range in the first 4 weeks of therapy. Conclusion The COAG will determine if genetic information provides added benefit above and beyond clinical information alone. (Am Heart J 2013;166:435-441.e2.) PMID:24016491

  3. Anticoagulation management during cross-clamping and bypass.

    PubMed

    Lander, H; Zammert, M; FitzGerald, D

    2016-09-01

    Anticoagulation is required for successful implementation of cardiopulmonary bypass (CPB), as well as for surgeries requiring temporary aortic occlusion. It is well established that both coagulation and fibrinolysis are activated during CPB (Teufelsbauer et al., 1992) [1]. Appropriate dosing, monitoring, and maintenance of anticoagulation are essential to prevent devastating thrombosis of the CPB circuit or the occluded aorta and to minimize the activation of the hemostatic system. Although numerous novel anticoagulants have been developed over the past decade, unfractionated heparin remains the primary anticoagulant utilized during these types of procedures, with monitoring systems primarily based upon the activated clotting time and/or heparin concentration. This article will review the current state of anticoagulation management during cross-clamp and CPB. PMID:27650345

  4. Self management of oral anticoagulation: randomised trial

    PubMed Central

    Fitzmaurice, D A; Murray, E T; McCahon, D; Holder, R; Raftery, J P; Hussain, S; Sandhar, H; Hobbs, F D R

    2005-01-01

    Objective To determine the clinical effectiveness of self management compared with routine care in patients on long term oral anticoagulants. Design Multicentre open randomised controlled trial. Setting Midlands region of the UK. Participants 617 patients aged over 18 and receiving warfarin randomised to intervention (n = 337) and routine care (n = from 2470 invited; 193/337 (57%) completed the 12 month intervention. Intervention Intervention patients used a point of care device to measure international normalised ratio twice a week and a simple dosing chart to interpret their dose of warfarin. Main outcome measure Percentage of time spent within the therapeutic range of international normalised ratio. Results No significant differences were found in percentage of time in the therapeutic range between self managment and routine care (70% v 68%). Self managed patients with poor control before the study showed an improvement in control that was not seen in the routine care group. Nine patients (2.8/100 patient years) had serious adverse events in the self managed group, compared with seven (2.7/100 patient years) in the routine care arm (χ2(df = 1) = 0.02, P = 0.89). Conclusion With appropriate training, self management is safe and reliable for a sizeable proportion of patients receiving oral anticoagulation treatment. It may improve the time spent the therapeutic range for patients with initially poor control. Trial registration ISRCTN 19313375. PMID:16216821

  5. Anticoagulant Heparan Sulfate: Structural Specificity and Biosynthesis

    PubMed Central

    Liu, Jian; Pedersen, Lars C.

    2007-01-01

    Summary Heparan sulfate (HS) is present on the surface of endothelial and surrounding tissues in large quantities. It plays important roles in regulating numerous functions of the blood vessel wall, including blood coagulation, inflammation response and cell differentiation. HS is a highly sulfated polysaccharide containing glucosamine and glucuronic/iduronic acid repeating disaccharide units. The unique sulfated saccharide sequences of HS determine its specific functions. Heparin, an analogue of heparan sulfate, is the most commonly used anticoagulant drug. Because of its wide range of biological functions, HS has become an interesting molecule to biochemists, medicinal chemists and developmental biologists. Here, we summarize recent progress towards understanding the interaction between heparan sulfate and blood coagulating factors, the biosynthesis of anticoagulant heparan sulfate and the mechanism of action of heparan sulfate biosynthetic enzymes. Further, knowledge of the biosynthesis of HS facilitates the development of novel enzymatic approaches to synthesize HS from bacterial capsular polysaccharides and to produce polysaccharide end products with high specificity for the biological target. These advancements provide the foundation for the development of polysaccharide-based therapeutic agents. PMID:17131147

  6. Nebulized anticoagulants limit coagulopathy but not inflammation in pseudomonas aeruginosa-induced pneumonia in rats.

    PubMed

    Cornet, Alexander D; Hofstra, Jorrit J; Vlaar, Alexander P; van den Boogaard, Floor E; Roelofs, Joris J; van der Poll, Tom; Levi, Marcel; Groeneveld, A B Johan; Schultz, Marcus J

    2011-10-01

    Disturbed alveolar fibrin turnover is a characteristic feature of pneumonia. Inhibitors of coagulation could exert lung-protective effects via anticoagulant (inhibiting fibrin deposition) and possibly anti-inflammatory pathways, but could also affect host defense. In this randomized controlled in vivo laboratory study, rats were challenged intratracheally with Pseudomonas aeruginosa, inducing pneumonia, and randomized to local treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin, or danaparoid. Induction of P. aeruginosa pneumonia resulted in activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as reflected by increased pulmonary levels of thrombin-AT complexes and fibrin degradation products and decreased pulmonary levels plasminogen activator activity. Pseudomonas aeruginosa pneumonia was accompanied by systemic coagulopathy, since systemic levels of thrombin-AT complexes increased, and systemic levels of plasminogen activator activity decreased. Although rh-APC and plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor danaparoid affected net pulmonary fibrin turnover. Recombinant human APC also displayed systemic anticoagulant effects. Neither bacterial clearance nor pulmonary inflammation was affected by anticoagulant therapy. Nebulization of rh-APC or plasma-derived AT attenuated pulmonary coagulopathy, but not bacterial clearance or inflammation, in a rat model of P. aeruginosa pneumonia. PMID:21897338

  7. [Acute and chronic anticoagulation therapy in relation to joint replacements].

    PubMed

    Malý, Jaroslav

    2015-06-01

    Thromboembolic disease (TED) is a considerable social and health problem. The solution evidently consists in the prevention of TED in clinical fields, not in the treatment itself. We can assume that effective prevention consequently reduces the cost of the following treatment. A lethal pulmonary embolism (PE) can be the first and the final clinical manifestation in patients with an asymptomatic deep venous thrombosis. This makes the systematic prevention of venous thromboembolism in higher risk patients necessary. Unfortunately, pharmacological prevention has been used less than would be needed. Inseparable from the TED prevention are physical methods. Pharmacological possibilities of the thromboembolic disease prevention were significantly extended within the past decade. To ensure the TED prevention after the total replacement (TEP) of hip and knee joints the following rules need to be observed: the TED prevention should be effected with LMWH, fondaparinux, dabigatran, rivaroxaban or apixaban for a period of 28-35 days after the hip joint replacement surgery and for 14 days after the knee joint replacement. The use of ASA, dextran and UFH as a thromboprophylaxis after the hip and knee joint TEP is not justified within the Czech Republic. Physical means (graduated compression stockings or IPC) can be used to support the recommended pharmacological treatment, they should not be used individually except in cases where pharmacological thromboprophylaxis is contraindicated.Key words: apixaban - dabigatran - LMWH - rivaroxaban - total hip and knee joint replacement - thromboembolic disease. PMID:26258975

  8. Use of Anticoagulants and Antiplatelet Agents in Stable Outpatients with Coronary Artery Disease and Atrial Fibrillation. International CLARIFY Registry

    PubMed Central

    Fauchier, Laurent; Greenlaw, Nicola; Ferrari, Roberto; Ford, Ian; Fox, Kim M.; Tardif, Jean-Claude; Tendera, Michal; Steg, Ph. Gabriel

    2015-01-01

    Background Few data are available regarding the use of antithrombotic strategies in coronary artery disease patients with atrial fibrillation (AF) in everyday practice. We sought to describe the prevalence of AF and its antithrombotic management in a contemporary population of patients with stable coronary artery disease. Methods and Findings CLARIFY is an international, prospective, longitudinal registry of outpatients with stable coronary artery disease, defined as prior (≥12 months) myocardial infarction, revascularization procedure, coronary stenosis >50%, or chest pain associated with evidence of myocardial ischemia. Overall, 33,428 patients were screened, of whom 32,954 had data available for analysis at baseline; of these 2,229 (6.7%) had a history of AF. Median (interquartile range) CHA2DS2-VASc score was 4 (3, 5). Oral anticoagulation alone was used in 25.7%, antiplatelet therapy alone in 52.8% (single 41.8%, dual 11.0%), and both in 21.5%. OAC use was independently associated with permanent AF (p<0.001), CHA2DS2-VASc score (p=0.006), pacemaker (p<0.001), stroke (p=0.04), absence of angina (p=0.004), decreased left ventricular ejection fraction (p<0.001), increased waist circumference (p=0.005), and longer history of coronary artery disease (p=0.008). History of percutaneous coronary intervention (p=0.004) and no/partial reimbursement for cardiovascular medication (p=0.01, p<0.001, respectively) were associated with reduced oral anticoagulant use. Conclusions In this contemporary cohort of patients with stable coronary artery disease and AF, most of whom are theoretical candidates for anticoagulation, oral anticoagulants were used in only 47.2%. Half of the patients received antiplatelet therapy alone and one-fifth received both antiplatelets and oral anticoagulants. Efforts are needed to improve adherence to guidelines in these patients. Trial Registration ISRCTN registry of clinical trials: ISRCTN43070564. PMID:25915904

  9. A survival case of painless chronic type A aortic dissection with a history of stroke and anticoagulant use.

    PubMed

    Tugcu, Aylin; Yildirimturk, Ozlem; Demiroglu, I C Cemsid; Aytekin, Saide

    2010-10-01

    We report the case of a patient with completely painless chronic aortic dissection, who presented to another hospital with a left hemiparesia 3 months ago and received anticoagulation therapy with a diagnosis of ischemic stroke. Most of her symptoms had resolved when she presented to our outpatient clinic except for numbness of her left hand and dysphasia. Physical examination found a diastolic murmur at the left sternal border and a bruit over the right carotid artery. Transthoracic echocardiography and carotid sonography demonstrated aortic dissection with extension into the internal right carotid artery and severe aortic regurgitation. Surgery was performed successfully and the patient was discharged. This case emphasizes that the diagnosis of a completely painless aortic dissection with only neurologic symptoms at presentation can be extremely difficult and should always be considered as a cause of ischemic stroke to avoid catastrophic antithrombolytic or anticoagulation therapy. PMID:20872939

  10. Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review.

    PubMed

    Violi, Francesco; Lip, Gregory Yh; Pignatelli, Pasquale; Pastori, Daniele

    2016-03-01

    Educational advice is often given to patients starting treatment with vitamin K Antagonists (VKAs). A great emphasis is made on nutritional information. Common belief is that dietary vitamin K intake could counteract the anticoagulant effect by VKAs and for many years, patients have been discouraged to consume vitamin-K-rich foods, such as green leafy vegetables.The objective of this study is to summarize the current evidence supporting the putative interaction between dietary vitamin K intake and changes in INR with the VKAs.Data sources are MEDLINE via PubMed and Cochrane database.All clinical studies investigating the relationship between dietary vitamin K and measures of anticoagulation were included. We excluded all studies of supplementation of vitamin K alone.We performed a systematic review of the literature up to October 2015, searching for a combination of "food," "diet," "vitamin K," "phylloquinone," "warfarin," "INR," "coagulation," and "anticoagulant."Two dietary interventional trials and 9 observational studies were included. We found conflicting evidence on the effect of dietary intake of vitamin K on coagulation response. Some studies found a negative correlation between vitamin K intake and INR changes, while others suggested that a minimum amount of vitamin K is required to maintain an adequate anticoagulation. Median dietary intake of vitamin K1 ranged from 76 to 217 μg/day among studies, and an effect on coagulation may be detected only for high amount of vitamin intake (>150 μg/day).Most studies included patients with various indications for VKAs therapy, such as atrial fibrillation, prosthetic heart valves, and venous thromboembolism. Thus, INR target was dishomogeneous and no subanalyses for specific populations or different anticoagulants were conducted. Measures used to evaluate anticoagulation stability were variable.The available evidence does not support current advice to modify dietary habits when starting therapy with VKAs

  11. Oral anticoagulation to prevent thrombosis recurrence in polycythemia vera and essential thrombocythemia.

    PubMed

    Hernández-Boluda, Juan-Carlos; Arellano-Rodrigo, Eduardo; Cervantes, Francisco; Alvarez-Larrán, Alberto; Gómez, Montse; Barba, Pere; Mata, María-Isabel; González-Porras, José-Ramón; Ferrer-Marín, Francisca; García-Gutiérrez, Valentín; Magro, Elena; Moreno, Melania; Kerguelen, Ana; Pérez-Encinas, Manuel; Estrada, Natàlia; Ayala, Rosa; Besses, Carles; Pereira, Arturo

    2015-06-01

    It is unclear whether anticoagulation guidelines intended for the general population are applicable to patients with polycythemia vera (PV) and essential thrombocythemia (ET). In the present study, the risk of thrombotic recurrence was analyzed in 150 patients with PV and ET treated with vitamin K antagonists (VKA) because of an arterial or venous thrombosis. After an observation period of 963 patient-years, the incidence of re-thrombosis was 4.5 and 12 per 100 patient-years under VKA therapy and after stopping it, respectively (P < 0.0005). After a multivariate adjustment for other prognostic factors, VKA treatment was associated with a 2.8-fold reduction in the risk of thrombotic recurrence. Notably, VKA therapy offset the increased risk of re-thrombosis associated with a prior history of remote thrombosis. Both the protective effect of VKA therapy and the predisposing factors for recurrence were independent of the anatomical site involved in the index thrombosis. Treatment periods with VKA did not result in a higher incidence of major bleeding as compared with those without VKA. These findings support the use of long-term anticoagulation for the secondary prevention of thrombosis in patients with PV and ET, particularly in those with history of remote thrombosis.

  12. [Antidotes to novel direct oral anticoagulants].

    PubMed

    Khorev, N G; Momot, A P; Kon'kova, V O

    2016-01-01

    During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation). The review contains the data on the existing therapeutic regimens of treating haemorrhage on the background of taking these coagulants. This is followed by analysing the present-day results of clinical trials aimed at working out pharmaceutical agents (andexanet alpha, idarucizumab, aripazine) being antidotes to direct thrombin inhibitor and the factor Xa inhibitors. Administration of these agents makes it possible to reverse coagulation and minimize the aftermaths of haemorrhage in patients taking these drugs, in emergency situations. PMID:27626268

  13. Thromboembolism and anticoagulation after Fontan surgery.

    PubMed

    Viswanathan, Sangeetha

    2016-01-01

    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

  14. Thromboembolism and anticoagulation after Fontan surgery.

    PubMed

    Viswanathan, Sangeetha

    2016-01-01

    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.

  15. Thromboembolism and anticoagulation after Fontan surgery

    PubMed Central

    Viswanathan, Sangeetha

    2016-01-01

    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

  16. Thromboembolism and anticoagulation after Fontan surgery

    PubMed Central

    Viswanathan, Sangeetha

    2016-01-01

    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.

  17. Outcomes of retrievable inferior vena cava filters in patients with deep vein thrombosis and transient contraindication for anticoagulation

    PubMed Central

    Kim, Hyung-Kee; Song, Incheol; Jang, Ji-Hoon; Oh, Chang-Wug; Lee, Jong-Min

    2015-01-01

    Purpose To determine the efficacy of a retrievable inferior vena cava filter (IVCF) for patients with deep vein thrombosis (DVT) and transient contraindication for anticoagulant therapy, and to analyze the risk factors for filter thrombus in these patients. Methods We retrospectively reviewed the records of 70 patients who received a retrievable IVCF from January 2007 to June 2014 because of documented DVT and transient contraindication for anticoagulant therapy. The protocol for follow-up care generally consisted of anticoagulant therapy after high-risk periods, follow-up CT around 2 weeks after IVCF placement, and retrieval if possible. Results The 70 patients had a mean age of 61.8 years (range, 17-88 years), and 30 were male (43%). The indications for IVCF were recent trauma including surgery in 48 patients, recent hemorrhage in 14, and planned major surgery with DVT in 8 patients. Follow-up CT of 61 patients (87%) was performed. Aggravation or new development of pulmonary embolism (PE) was not found in any patient. Filter thrombus was detected in 23% of patients with follow-up CT (14/61). Filter thrombus was not detected in patients with isolated calf vein thrombosis (ICVT) (P = 0.079). The risk factor for filter thrombus was DVT progression on follow-up CT (P = 0.007) on multivariate analysis. Conclusion For patients with DVT and transient contraindication for anticoagulant therapy, a retrievable IVCF could prevent the aggravation or new development of PE. DVT progression on follow-up CT was associated with filter thrombus and ICVT was not related to filter thrombus in the present study. PMID:26131442

  18. The management of dental patients taking new generation oral anticoagulants.

    PubMed

    Scott, Alun; Gibson, John; Crighton, Alexander

    2014-11-01

    Recently, new oral anticoagulants have been introduced as alternatives to warfarin. While national guidelines for treatment of dental patients taking warfarin as an anticoagulant are well-established, no such information is available for these novel therapeutic agents. At present, the local guidance available is contradictory between different health boards/health planning units, and liaison with the medical practitioner managing the individual patient's anticoagulation is imperative if any invasive procedure is proposed. This paper examines the available evidence regarding these drugs and sets out proposals for clinical guidance of dental practitioners treating these patients in primary dental care. PMID:25668377

  19. Bleeding events associated with novel anticoagulants: a case series.

    PubMed

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

    2013-12-01

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

  20. Unplanned pregnancy on a direct oral anticoagulant (Rivaroxaban): A warning.

    PubMed

    Myers, B; Neal, R; Myers, O; Ruparelia, M

    2016-03-01

    Direct oral anticoagulants (DOACs or NOACs -non-vitamin K oral anticoagulants), as the name suggests, are oral anticoagulants with a direct inhibitory action either against factor X or factor II (thrombin). Pregnant women were excluded from participating in all the large trials of the DOACs and they are considered contra-indicated in pregnancy and breast feeding. We present a case of inadvertent exposure to rivaroxaban in a woman who presented at 25 weeks' gestation. The management of her pregnancy and delivery is described, and the previous published case reports are reviewed with a discussion about the use of DOACs in woman of childbearing age. PMID:27512489

  1. Synthetic oligosaccharides as heparin-mimetics displaying anticoagulant properties.

    PubMed

    Avci, Fikri Y; Karst, Nathalie A; Linhardt, Robert J

    2003-01-01

    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

  2. Aligning health care policy with evidence-based medicine: the case for funding direct oral anticoagulants in atrial fibrillation.

    PubMed

    Stone, James A; Earl, Karen M; O'Neill, Blair J; Sharma, Mukul; Huynh, Thao; Leblanc, Kori; Ward, Richard; Teal, Philip A; Cox, Jafna L

    2014-10-01

    Misalignment between evidence-informed clinical care guideline recommendations and reimbursement policy has created care gaps that lead to suboptimal outcomes for patients denied access to guideline-based therapies. The purpose of this article is to make the case for addressing this growing access barrier to optimal care. Stroke prevention in atrial fibrillation (AF) is discussed as an example. Stroke is an extremely costly disease, imposing a significant human, societal, and economic burden. Stroke in the setting of AF carries an 80% probability of death or disability. Although two-thirds of these strokes are preventable with appropriate anticoagulation, this has historically been underprescribed and poorly managed. National and international guidelines endorse the direct oral anticoagulants as first-line therapy for this indication. However, no Canadian province has provided these agents with an unrestricted listing. These decisions appear to be founded on silo-based cost assessment-the drug costs rather than the total system costs-and thus overlook several important cost-drivers in stroke. The discordance between best scientific evidence and public policy requires health care providers to use a potentially suboptimal therapy in contravention of guideline recommendations. It represents a significant obstacle for knowledge translation efforts that aim to increase the appropriate anticoagulation of Canadians with AF. As health care professionals, we have a responsibility to our patients to engage with policy-makers in addressing and resolving this barrier to optimal patient care.

  3. Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation.

    PubMed

    Borgman, Mark P; Pendleton, Robert C; McMillin, Gwendolyn A; Reynolds, Kristen K; Vazquez, Sara; Freeman, Andrew; Wilson, Andrew; Valdes, Roland; Linder, Mark W

    2012-09-01

    We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient's genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management. PMID:22836303

  4. [Anticoagulation for patients with non-valvular atrial fibrillation].

    PubMed

    Mizoguchi, Tadataka; Yasaka, Masahiro

    2016-04-01

    Non-valvular atrial fibrillation (NVAF) is the most common cardiac source of emboli in cardioembolic stroke which occupies from 1/4 to 1/3 of acute brain infarction in Japan. Non-vitamin K antagonist oral anticoagulants (NOAC) have been used widely because they are easy to use, their effect in preventing ischemic stroke is higher than or as high as warfarin, their incidence of major hemorrhage is lower than or as low as warfarin, and their incidence of intracranial hemorrhage is much lower than warfarin. However, there seem several issues to address regarding NOAC treatment, such as reversal of anticoagulation, antidotes, monitoring of anticoagulation, rt-PA treatment for acute stroke patients treated with NOACs. In this review, current strategies and issues of anticoagulation for prevention of stroke in NVAF are discussed. PMID:27333751

  5. Pharmacogenetic typing for oral anti-coagulant response among factor V Leiden mutation carriers

    PubMed Central

    Nahar, Risha; Saxena, Renu; Deb, Roumi; Verma, Ishwar C.

    2012-01-01

    CONTEXT: Factor V Leiden mutation is the most common inherited predisposition for hypercoagulability and thereby a common genetic cause for initiation of oral anti-coagulation therapy. There is a dearth of knowledge of coumarin response profile in such thrombophilic population. AIMS: The current pilot study aims to estimate coumarin sensitivity in an Indian cohort with an inherited thrombophilia risk factor (Factor V Leiden mutation carriers) based on the observed frequency of CYP2C9 *2, *3 and VKORC1-1639G >A genotype combinations. SETTINGS AND DESIGN: A retrospective study carried out in a tertiary health care center in India. MATERIALS AND METHODS: Carriers of FVL mutation were genotyped for CYP2C9 (*2, F*3) and VKORC1 (-1639G >A) variants by PCR-RFLP technique. STATISTICAL ANALYSIS USED: Chi-square test to analyze difference in expected and observed genotype frequency. RESULTS: Sixty-one (n = 61) unrelated carriers of FVL mutation were observed in the 13 years study period. The allele frequency of CYP2C9 *2, CYP2C9 *3, and VKORC1-1639A in this cohort was 0.06, 0.11, and 0.16, respectively. Six (9.7%) individuals had two of the three variant alleles (heterozygous or homozygous), and 28 (45.9%) were heterozygous for at least one polymorphism. CONCLUSIONS: Pre-prescription genotyping for coumarin drugs, if introduced in Indians with inherited thrombophilia (in whom oral anti-coagulant therapy may be necessary), is likely to identify 9.7% (hypersensitive) subjects in whom the optimum anti-coagulation may be achieved with reduced dosages, 44.3% (normal sensitivity) who may require higher dose and also 55.6% (hyper and moderate sensitivity) subjects who are likely to experience bleeding episodes. PMID:23716941

  6. Addressing Barriers to Optimal Oral Anticoagulation Use and Persistence Among Patients with Atrial Fibrillation: Proceedings, Washington, DC, December 3–4, 2012

    PubMed Central

    Hess, Paul L.; Mirro, Michael J.; Diener, Hans-Christoph; Eikelboom, John W.; Al-Khatib, Sana M.; Hylek, Elaine M.; Bosworth, Hayden B.; Gersh, Bernard J.; Singer, Daniel E.; Flaker, Greg; Mega, Jessica L.; Peterson, Eric D.; Rumsfeld, John S.; Steinberg, Benjamin A.; Kakkar, Ajay K.; Califf, Robert M.; Granger, Christopher B.

    2014-01-01

    Approximately half of patients with atrial fibrillation (AF) and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3–4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to develop and disseminate shared decision-making tools, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational datasets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives. PMID:25173533

  7. Development and Validation of an Oral Anticoagulation Knowledge Tool (AKT)

    PubMed Central

    Obamiro, Kehinde O.; Chalmers, Leanne; Bereznicki, Luke R. E.

    2016-01-01

    Background Assessing and improving patients’ anticoagulation knowledge can lead to better treatment outcomes. While validated knowledge instruments exist for use in people taking warfarin, these tools are not necessarily applicable to patients taking direct-acting oral anticoagulants. Objective To develop and validate an oral anticoagulation knowledge instrument that is applicable to all oral anticoagulant medications. Methods Ten anticoagulation experts participated in the development of the Anticoagulation Knowledge Tool to ensure content validity. The knowledge instrument was administered to three groups of participants comprising of 44 pharmacists, 50 patients and 50 members of the general public. A subgroup of participants in the patient and pharmacist group were retested approximately 2–3 months after the initial testing. Statistical tests were conducted to determine the validity and reliability of the scale, and item analysis was used to determine the performance of individual questions. Results The 28-item instrument developed had a scale content validity index of 0.92, supporting content validity. The pharmacist group’s mean score was significantly higher than that of the patient group, and the patient group scored significantly higher than the general public group (94% vs 62% vs 20%, respectively; p<0.001), supporting construct validity. Internal consistency reliability was acceptable with a Cronbach’s α value of > 0.7 across the three groups, and the test–retest reliability was confirmed with a Pearson’s correlation coefficient of 0.72 and 0.78 for the pharmacist and patient groups, respectively. Conclusion The Anticoagulation Knowledge Tool is a valid and reliable instrument that can be used in routine clinical practice to assess patients’ anticoagulation knowledge. PMID:27351746

  8. Evaluation of intraoperative anticoagulants in microvascular free-flap surgery.

    PubMed Central

    Pugh, C. M.; Dennis, R. H.; Massac, E. A.

    1996-01-01

    This retrospective study evaluated anticoagulants used during surgery to determine efficacy and associated complications. The patient population was comprised of 15 patients who underwent microvascular free-flap surgery for wound coverage of the lower one third of the leg. Results indicated that the use of heparin in conjunction with other anticoagulants was associated with the development of more hematomas compared with the use of aspirin and dextran, both separately and together. PMID:8918071

  9. Beyond heparin and warfarin: the new generation of anticoagulants.

    PubMed

    Weitz, Jeffrey I; Linkins, Lori-Ann

    2007-03-01

    Heparin and warfarin are widely used for the prevention and treatment of venous and arterial thromboembolism. Although effective, both agents have important limitations; for example, both drugs must be monitored, which is inconvenient for patients and for physicians. Heparin requires parenteral administration and can cause heparin-induced thrombocytopenia, an immune-mediated process that can lead to life-threatening thrombosis. Warfarin also has its limitations. Due to its slow onset of action, warfarin must be overlapped with heparin (or another rapidly acting anticoagulant) when treating patients with established thrombosis or who are at high risk for thrombosis. Warfarin dosing is variable because its activity is influenced by dietary intake of vitamin K, genetic polymorphisms in enzymes that are involved in its metabolism and numerous drug-drug interactions that promote or reduce its activity. New anticoagulants have been developed to overcome these problems. Building on a better understanding of coagulation pathways, advances in structure-based drug design and information derived from natural anticoagulants isolated from hematophagous organisms, most of the new anticoagulants target specific coagulation enzymes. Focussing on drugs that have at least completed Phase II evaluation, this article briefly reviews the coagulation pathways and its natural regulators; outlines the limitations of existing anticoagulants and identifies the opportunities for new ones; highlights the properties of selected new anticoagulants; describes the clinical trial results with these agents; and provides a perspective on their potential strengths and weaknesses. PMID:17302522

  10. Laboratory measurement of the anticoagulant activity of edoxaban: a systematic review.

    PubMed

    Cuker, Adam; Husseinzadeh, Holleh

    2015-04-01

    Edoxaban, an oral direct inhibitor of factor Xa, was recently approved in the United States and Japan for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism (VTE). It is also licensed in Japan for prevention of VTE after major orthopedic surgery. Although routine laboratory monitoring of edoxaban is not required, laboratory measurement may be desirable in special circumstances. Our objective was to provide a systematic review of current evidence on laboratory measurement of the anticoagulant activity of edoxaban. PubMed and the Cochrane Library were searched for studies that reported a relationship between coagulation tests and plasma edoxaban levels. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We identified 9 eligible studies. Anti-Xa activity is linear across a broad range of drug levels (R (2) > 0.95) and may be used for edoxaban quantification. The assay shows greater variability at above on-therapy drug concentrations. The PT is less sensitive to edoxaban. A normal prothrombin time may not exclude clinically relevant on-therapy drug levels. The activated partial thromboplastin time has insufficient sensitivity to edoxaban for measurement of its anticoagulant activity. Edoxaban exhibits variable effects on coagulation assays. Understanding these effects facilitates interpretation of test results in edoxaban-treated patients. More data on the relationship between drug levels, coagulation test results, and clinical outcomes in patients are needed. PMID:25669624

  11. Deep vein thrombosis after total knee arthroplasty in asian patients without prophylactic anticoagulation.

    PubMed

    Chung, Lien-Hsiang; Chen, Wei-Ming; Chen, Cheng-Fong; Chen, Tain-Hsiung; Liu, Chien-Lin

    2011-01-01

    Deep vein thrombosis (DVT) is an important complication following total knee arthroplasty (TKA). However, the incidence of DVT is generally underestimated due to subclinical or minor symptoms and signs. In Western countries, prophylactic agents against DVT are administered routinely after TKA. However, in Asia, no regular prophylaxis is generally given to patients undergoing TKA. This article presents a prospective study evaluating the incidence of DVT in 724 consecutive Taiwanese patients who underwent TKA without prophylactic anticoagulation therapy. Of these, 328 patients (45.3%) showed positive Homan's sign with calf swelling >3 cm. Ultrasonographic examination revealed the overall incidence of DVT to be 8.6% (62/724). The incidence of DVT was significantly higher in women (P=.035), in patients who underwent bilateral TKA (P=.002), and in patients with a body mass index ≥30 kg/m(2) (P=.026). The incidence of DVT appeared to be increased in patients with higher tourniquet time; however, the difference was not statistically significant. In all of the suspected cases of DVT, the symptoms subsided after the administration of enoxaparin with uneventful follow-up. No patient developed pulmonary embolism. Our results showed a relatively high incidence of DVT in an Asian population following TKA. We therefore consider that following TKA, prophylactic anticoagulation therapy should be administered to high-risk patients.

  12. Anticoagulation: where have we come from and where are we going? The evidence for and against novel anticoagulants.

    PubMed

    Symons, G

    2014-02-01

    Warfarin, one of the vitamin K antagonists, has been used since 1940, when it was first approved for the treatment of venous thromboembolism. It is currently the most commonly used anticoagulant, although alternative drugs are available, such as aspirin, clopidogrel and dipyridamol, which have been studied in a number of scenarios. The newest agents available to clinicians are the broad group of novel anticoagulants, such as direct thrombin and direct factor Xa inhibitors, including molecules such as dabigatran, rivaroxaban, apixaban and edoxaban.

  13. Do anticoagulation management services improve care? Implications of the Managing Anticoagulation Services Trial.

    PubMed

    Matchar, David B

    2003-12-01

    An Anticoagulation Clinic Service (ACS) has been proposed as one strategy for improving warfarin treatment for patients with atrial fibrillation. In the Managing Anticoagulation Services Trial (MAST), ACSs meeting specifications for high quality care were established in six managed care organizations (MCOs) which had the patients and resources to support this initiative. The trial followed 1165 patients age >or=65 years who had atrial fibrillation as the primary reason for anticoagulation and were enrolled in a participating MCO. The 593 patients in the intervention group saw physicians in a practice cluster which had randomly been assigned to have access to an ACS. These physicians used the ACS on average for about 48% of eligible patients. The 572 patients in the control group received care from physicians in a practice cluster which could not refer patients to the ACS established for the trial but was otherwise unrestricted. The two clusters were compared on the proportion of time warfarin-treated patients were in the target range (2-3) prothrombin time-international normalized ratio (INR) during a 9-month baseline and a 9-month follow-up period. Among patients ( n = 264) for whom data were available for both periods, the changes in percentages of time in the target range were similar in the intervention cluster (baseline: 47.7%; follow-up 55.6%) and in the control cluster (baseline: 49.1%; follow-up: 52.3%; intervention effect: 5%; 95% confidence interval: -5% to 14%; P = 0.32). In both practice clusters, patients had subtherapeutic INR values (1.5 to 1.99) about one fourth of the time. Providing an ACS in a managed care setting did not appear to improve anticoagulation care over the usual care provided at the sites in this trial but could be a reasonable consideration in a practice setting where time in target range is less than 50%. A higher rate of utilization and a more aggressive stance toward subtherapeutic INR values could potentially enhance the

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

    PubMed Central

    2011-01-01

    Background Warfarin nomograms to guide dosing have been shown to improve control of the international normalized ratio (INR) in the general outpatient setting. However, the effectiveness of these nomograms in hemodialysis patients is unknown. We evaluated the effectiveness of anticoagulation using an electronic warfarin nomogram administered by nurses in outpatient hemodialysis patients, compared to physician directed therapy. Methods Hemodialysis patients at any of the six outpatient clinics in Calgary, Alberta, treated with warfarin anticoagulation were included. Two five-month time periods were compared: prior to and post implementation of the nomogram. The primary endpoint was adequacy of anticoagulation (proportion of INR measurements within range ± 0.5 units). Results Overall, 67 patients were included in the pre- and 55 in the post-period (with 40 patients in both periods). Using generalized linear mixed models, the adequacy of INR control was similar in both periods for all range INR levels: in detail, range INR 1.5 to 2.5 (pre 93.6% (95% CI: 88.6% - 96.5%); post 95.6% (95% CI: 89.4% - 98.3%); p = 0.95); INR 2.0 to 3.0 (pre 82.2% (95% CI: 77.9% - 85.8%); post 77.4% (95% CI: 72.0% - 82.0%); p = 0.20); and, INR 2.5 to 3.5 (pre 84.3% (95% CI: 59.4% - 95.1%); post 66.8% (95% CI: 39.9% - 86.0%); p = 0.29). The mean number of INR measurements per patient decreased significantly between the pre- (30.5, 95% CI: 27.0 - 34.0) and post- (22.3, 95% CI: 18.4 - 26.1) (p = 0.003) period. There were 3 bleeding events in each of the periods. Conclusions An electronic warfarin anticoagulation nomogram administered by nurses achieved INR control similar to that of physician directed therapy among hemodialysis patients in an outpatient setting, with a significant reduction in frequency of testing. Future controlled trials are required to confirm the efficacy of this nomogram. PMID:21943221

  15. Approach to the new oral anticoagulants in family practice

    PubMed Central

    Douketis, James; Bell, Alan David; Eikelboom, John; Liew, Aaron

    2014-01-01

    Abstract Objective To address common “what if” questions that arise relating to the long-term clinical follow-up and management of patients receiving the new oral anticoagulants (NOACs). Sources of information For this narrative review, we searched the PubMed database for recent (January 2008 to week 32 of 2013) clinical studies relating to NOAC use for stroke prevention in atrial fibrillation and for the treatment of acute venous thromboembolism. We used this evidence base to address prespecified questions relating to NOAC use in primary care settings. Main message Dabigatran and rivaroxaban should be taken with meals to decrease dyspepsia and increase absorption, respectively. There are no dietary restrictions with any of the NOACs, beyond moderating alcohol intake, and rivaroxaban and apixaban can be crushed if required. The use of acid suppressive therapies does not appear to affect the efficacy of the NOACs. As with warfarin, patients taking NOACs should avoid long-term use of nonsteroidal anti-inflammatory and antiplatelet drugs. For patients requiring surgery, generally NOACs should be stopped 2 to 5 days before the procedure, depending on bleeding risk, and the NOAC should usually be resumed at least 24 hours after surgery. Preoperative coagulation testing is generally unnecessary. In patients who develop bleeding, minor bleeding typically does not require laboratory testing or discontinuation of NOACs; with major bleeding, the focus should be on local measures to control the bleeding and supportive care, and coagulation testing should be performed. There are currently no antidotes to reverse NOACs. The NOACs should not be used in patients with valvular heart disease, prosthetic heart valves, cancer-associated deep vein thrombosis, or superficial thrombophlebitis. Conclusion Management of “what if” scenarios for patients taking NOACs have been proposed, but additional study is needed to address these issues, especially periprocedural management and

  16. Apixaban: a new player in the anticoagulant class.

    PubMed

    Agrawal, Ritesh; Jain, Pratima; Dikshit, S N

    2012-06-01

    Apixaban (BMS-562247-01) is a compound being investigated as an anticoagulant. Apixaban molecule is developed in a joint venture by Pfizer and Bristol-Myers Squibb. Apixaban, a coagulation factor Xa inhibitor, approved in the E.U. in 2011 for the prevention of venous thromboembolic events in adult patients, who have undergone elective hip or knee replacement. The Apixaban based drug will be marketed under the brand name Eliquis® and is expected to rack up annual sales of over $2.5 billion. Apixaban is expected to provide stiff competition to warfarin, a popular blood thinner used in Europe. Warfarin is known to cause some serious side effects in patients. Apixaban, as compared with aspirin, reduced the risk of stroke or systemic embolism in patients experiencing atrial fibrillation by more than 50% (from 3.7% per annum with aspirin to 1.6% per annum with apixaban). Apixaban exhibits superiority to enoxaparin in preventing thrombosis in patients undergoing elective hip replacement surgery with similar bleeding rates. Apixaban is a highly selective and potent Factor Xa Inhibitor with Ki=0 8nM to both free as well as prothrombinase bound FXa. In X-ray crystal structure studies indicate that the pyrazole N-2 nitrogen atom interacts with backbone of Gln192 and the carbonyl oxygen of carboxamide interacts with NH of Gly216. The orientation of phenyllactum in the S4 region indiacates an edge to face interaction with Trp215, which is positioned between the Tyr99 and Phe174. In the present review, we have tried to cover comparative study of various FXa-inhibitors and point out apixaban in the various aspect including molecular chemistry, physical properties, commercial synthesis, current patent status, crystalline polymorphic forms, molecular receptor interaction, pharmacophore rational, mechanism of action, clinical studies, preclinical, adverse effect, available formulation, dose regimen and co-therapy, thus giving emphasis on medicinal chemistry aspects.

  17. The Role of Nonvitamin K Antagonist Oral Anticoagulants (NOACs) in Stroke Prevention in Patients with Atrial Fibrillation.

    PubMed

    Kuznetsov, Sofya; Barcelona, Robert; Josephson, Richard A; Mohan, Sri K Madan

    2016-05-01

    Anticoagulation is important in stroke prevention in patients with atrial fibrillation. Until recently, heparins and vitamin K antagonists were the only available therapy for stroke reduction in atrial fibrillation (AF) patients. Non-vitamin K antagonist oral anticoagulants (NOACs) including direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are now available and offer new options for stroke prevention. This article reviews the available data on the use of NOACs for primary and secondary stroke prevention in AF patients and describes specific patient populations to guide clinician in making the informed decision regarding appropriate use of those agents. It also addresses the use of NOACs early after acute stroke and use of thrombolysis while on NOAC. PMID:27023335

  18. Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS).

    PubMed

    Gebhart, Johanna; Posch, Florian; Koder, Silvia; Perkmann, Thomas; Quehenberger, Peter; Zoghlami, Claudia; Ay, Cihan; Pabinger, Ingrid

    2015-05-28

    Data on the clinical course of lupus anticoagulant (LA)-positive individuals with or without thrombotic manifestations or pregnancy complications are limited. To investigate mortality rates and factors that might influence mortality, we conducted a prospective observational study of LA-positive individuals. In total, 151 patients (82% female) were followed for a median of 8.2 years; 30 of the patients (20%) developed 32 thromboembolic events (15 arterial and 17 venous events) and 20 patients (13%) died. In univariable analysis, new onset of thrombosis (hazard ratio [HR] = 8.76; 95% confidence interval [CI], 3.46-22.16) was associated with adverse survival. Thrombosis remained a strong adverse prognostic factor after multivariable adjustment for age and hypertension (HR = 5.95; 95% CI, 2.43-14.95). Concomitant autoimmune diseases, anticoagulant treatment at baseline, or positivity for anticardiolipin- or anti-β2-glycoprotein I antibodies were not associated with mortality. In a relative survival analysis, our cohort of LA positives showed a persistently worse survival in comparison with an age-, sex-, and study-inclusion-year-matched Austrian reference population. The cumulative relative survival was 95.0% (95% CI, 88.5-98.8) after 5 years and 87.7% (95% CI, 76.3-95.6) after 10 years. We conclude that occurrence of a thrombotic event is associated with higher mortality in patients with LA. Consequently, the prevention of thromboembolic events in LA positives might improve survival.

  19. Anticoagulation Management and Monitoring during Pediatric Extracorporeal Life Support: A Review of Current Issues

    PubMed Central

    Ryerson, Lindsay M.; Lequier, Laurence L.

    2016-01-01

    Anticoagulation is an imperfect science and is even more complicated in neonates and young children. The addition of the extracorporeal life support (ECLS) foreign circuit adds an additional layer of complexity. Anticoagulation goals during ECLS are to maintain a clot-free circuit and a hemostatically balanced patient. Unfractionated heparin (UFH) is the default gold standard anticoagulant as no large studies have been performed on any other anticoagulants. This review will focus on the advantages and disadvantages of the various methods to monitor UFH anticoagulation, discuss alternative anticoagulants, and examine bleeding and thrombotic complications during ECLS. PMID:27446890

  20. Anticoagulation Management and Monitoring during Pediatric Extracorporeal Life Support: A Review of Current Issues.

    PubMed

    Ryerson, Lindsay M; Lequier, Laurence L

    2016-01-01

    Anticoagulation is an imperfect science and is even more complicated in neonates and young children. The addition of the extracorporeal life support (ECLS) foreign circuit adds an additional layer of complexity. Anticoagulation goals during ECLS are to maintain a clot-free circuit and a hemostatically balanced patient. Unfractionated heparin (UFH) is the default gold standard anticoagulant as no large studies have been performed on any other anticoagulants. This review will focus on the advantages and disadvantages of the various methods to monitor UFH anticoagulation, discuss alternative anticoagulants, and examine bleeding and thrombotic complications during ECLS. PMID:27446890

  1. Anticoagulation for the prevention of stroke in non-valvular AF in general practice: room for improvement

    PubMed Central

    Ioannou, Adam; Metaxa, Sofia; Kassianos, George; Missouris, Constantinos G.

    2016-01-01

    Objective: Our aim was to assess whether the recommendations and guidelines for thromboprophylaxis in patients with atrial fibrillation (AF) have been adopted in general practice (GP). Methods: We conducted a retrospective study using the GP computer database (Hatfield, UK) on all 9400 patients to assess the quality of anticoagulation in patients with a recorded diagnosis of AF. Results: Of the 180 patients with a diagnosis of AF, 107 (59.4%) were treated with warfarin, 19 (10.6%) with a novel oral anticoagulant (NOAC), 31 (17.2%) with aspirin or clopidogrel, and 23 (12.8%) received none. Thirty-seven patients (34.6%) who were taking warfarin had a time in the therapeutic range (TTR) of less than 65%. Forty-five (27.6%) of the 163 patients who had a CHA2DS2VASc score of two or more were not prescribed a vitamin K antagonist (VKA) or a NOAC. None had a HAS-BLED greater than the CHA2DS2VASc score. Conclusion: Our study demonstrates that one in four patients with non-valvular AF, at risk of a stroke, is not being adequately treated with an oral anticoagulant in primary care. The majority were treated with warfarin, a third of which had a low TTR. A high proportion of patients are prescribed antiplatelet therapy instead. This is despite overwhelming evidence that VKAs and NOACs, and not aspirin or clopidogrel, improve outcome in patients with non-valvular AF. We suggest that a review of GP practice databases should be considered to identify patients with non-valvular AF, at risk of a disabling or fatal event, and measures taken to initiate anticoagulant therapy. PMID:27403193

  2. Low-Dose Heparin Anticoagulation During Extracorporeal Life Support for Acute Respiratory Distress Syndrome in Conscious Sheep

    PubMed Central

    Prat, Nicolas J.; Meyer, Andrew D.; Langer, Thomas; Montgomery, Robbie K.; Parida, Bijaya K.; Batchinsky, Andriy I.; Cap, Andrew P.

    2015-01-01

    ABSTRACT Background: Over 32% of burned battlefield causalities develop trauma-induced hypoxic respiratory failure, also known as acute respiratory distress syndrome (ARDS). Recently, 9 out of 10 US combat soldiers’ survived life-threatening trauma-induced ARDS supported with extracorporeal membrane oxygenation (ECMO), a portable form of cardiopulmonary bypass. Unfortunately, the size, incidence of coagulation complications, and the need for systematic anticoagulation for traditional ECMO devices have prevented widespread use of this lifesaving technology. Therefore, a compact, mobile, ECMO system using minimal anticoagulation may be the solution to reduce ARDS in critically ill military and civilian patients. Methods: We conducted a prospective cohort laboratory investigation to evaluate the coagulation function in an ovine model of oleic acid induced ARDS supported with veno-venous ECMO. The experimental design approximated the time needed to transport from a battlefield setting to an advanced facility and compared bolus versus standard heparin anticoagulation therapy. Results: Comprehensive coagulation and hemostasis assays did not show any difference because of ECMO support over 10 h between the two groups but did show changes because of injury. Platelet count and function did decrease with support on ECMO, but there was no significant bleeding or clot formation during the entire experiment. Conclusions: A bolus heparin injection is sufficient to maintain ECMO support for up to 10 h in an ovine model of ARDS. With a reduced need for systematic anticoagulation, ECMO use for battlefield trauma could reduce significant morbidity and mortality from ventilator-induced lung injury and ARDS. Future studies will investigate the mechanisms and therapies to support patients for longer periods on ECMO without coagulation complications. Level of Evidence: V—therapeutic animal experiment. PMID:26263439

  3. Spontaneous iliopsoas muscle haematoma as a complication of anticoagulation in acute cerebral venous thrombosis: to stop or not to stop (the anticoagulation)?

    PubMed

    Fernandes, Carina; Pereira, Pedro; Rodrigues, Miguel

    2015-01-01

    Spontaneous iliopsoas muscle haematoma is an infrequent complication of anticoagulation, potentially causing neurological dysfunction through compression of the femoral nerve or lumbar plexus. The authors report the case of a puerperal woman admitted for an extensive cerebral venous thrombosis. Anticoagulation was started, with clinical improvement. The patient later reported low back pain irradiating to the right thigh and developed neurological impairment consistent with lumbar plexus dysfunction. A pelvic CT scan revealed a right iliopsoas muscle haematoma. Considering the risk of anticoagulation suspension, a conservative approach was chosen, with maintenance of anticoagulation. Clinical and functional improvement occurred, with mild right hip and knee flexion paresis as sequelae. Anticoagulation complications are challenging, especially when interruption of anticoagulation may threaten vital and functional outcomes. Therefore, a careful evaluation is essential, since no clinical guidelines are available. In this case, continuing anticoagulation provided a good functional outcome. PMID:25750219

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

    PubMed Central

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

    2016-01-01

    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

  5. Risk of bleeding after dentoalveolar surgery in patients taking anticoagulants.

    PubMed

    Broekema, Ferdinand I; van Minnen, Baucke; Jansma, Johan; Bos, Rudolf R M

    2014-03-01

    To avoid increasing the risk of thromboembolic events, it is recommended that treatment with anticoagulants should be continued during dentoalveolar operations. We have evaluated the incidence of bleeding after dentoalveolar operations in a prospective study of 206 patients, 103 who were, and 103 who were not, taking anticoagulants. Seventy-one were taking thrombocyte aggregation inhibitors and 32 vitamin K antagonists. Patients were treated according to guidelines developed at the Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands. The operations studied included surgical extraction (when the surgeon had to incise the gingiva before extraction), non-surgical extraction, apicectomy, and placement of implants. Patients were given standard postoperative care and those taking vitamin K antagonists used tranexamic acid mouthwash postoperatively. No patient developed a severe bleed that required intervention. Seven patients (7%) taking anticoagulants developed mild postoperative bleeds. Patients taking vitamin K antagonists reported 3 episodes (9%) compared with 4 (6%) in the group taking thrombocyte aggregation inhibitors. Among patients not taking anticoagulants, two (2%) developed mild bleeding. The differences between the groups were not significant. All bleeding was controlled by the patients themselves with compression with gauze. We conclude that dentoalveolar surgery is safe in patients being treated with anticoagulants provided that the conditions described in the ACTA guidelines are met. PMID:24485810

  6. Marine sulfated glycans with serpin-unrelated anticoagulant properties.

    PubMed

    Glauser, Bianca F; Mourão, Paulo A S; Pomin, Vitor H

    2013-01-01

    Marine organisms are a rich source of sulfated polysaccharides with unique structures. Fucosylated chondroitin sulfate (FucCS) from the sea cucumber Ludwigothurea grisea and sulfated galactan from the red alga Botryocladia occidentalis are one of these unusual molecules. Besides their uncommon structures, they also exhibit high anticoagulant and antithrombotic effects. Earlier, it was considered that the anticoagulant activities of these two marine glycans were driven mainly by a catalytic serpin-dependent mechanism likewise the mammalian heparins. Its serpin-dependent anticoagulant action relies on promoting thrombin and/or factor Xa inhibition by their specific natural inhibitors (the serpins antithrombin and heparin cofactor II). However, as opposed to heparins, these two previously mentioned marine glycans were proved still capable in promoting coagulation inhibition using serpin-free plasmas. This puzzle observation was further investigated and clearly demonstrated that the cucumber FucCS and the red algal sulfated galactan have an unusual serpin-independent anticoagulant effect by inhibiting the formation of factor Xa and/or thrombin through the procoagulants tenase and prothrombinase complexes, respectively. These marine polysaccharides with unusual anticoagulant effects open clearly new perspectives for the development of new antithrombotic drugs as well as push the glycomics project.

  7. Anticoagulant rodenticide poisoning in animals of Apulia and Basilicata, Italy.

    PubMed

    Muscarella, Marilena; Armentano, Antonio; Iammarino, Marco; Palermo, Carmen; Amorena, Michele

    2016-06-30

    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

  8. Novel oral anticoagulants in secondary prevention of stroke.

    PubMed

    Diener, H C; Easton, J D; Hankey, G J; Hart, R G

    2013-06-01

    In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K antagonists (warfarin, phenprocoumon) is effective both for primary and secondary stroke prevention yielding a 60-70% relative reduction in stroke risk compared with placebo, as well as a mortality reduction of 26 percent. Vitamin-K antagonists have a number of well documented shortcomings. Recently the results of randomised trials for three new oral anticoagulants that do not exhibit the limitations of vitamin-K antagonists have been published. These include direct factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide promising results for the new agents, including higher efficacy and a significantly lower incidence of intracranial bleeds compared with warfarin or aspirin. The new drugs show similar results in secondary as well as in primary stroke prevention in patients with AF. Apixaban was demonstrated to be clearly superior to aspirin and had the same rate of major bleeding complications. Meta-analyses show that the novel anticoagulants are superior to warfarin for the reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants add to the therapeutic options for patients with AF, and offer a number of advantages over warfarin, for both the clinician and patient, including a favorable bleeding profile and convenience of use. Aspirin is no longer an option in secondary stroke prevention in patients with atrial fibrillation. Consideration of these new anticoagulants will improve clinical decision making. PMID:23953901

  9. Thrombotic and hemorrhagic complications in children with the lupus anticoagulant.

    PubMed

    Bernstein, M L; Salusinsky-Sternbach, M; Bellefleur, M; Esseltine, D W

    1984-12-01

    Endogenous circulating anticoagulants are unusual in children without a congenital factor deficiency. In particular, the lupus anticoagulant has only rarely been reported in children. Despite its functioning in vitro to prolong the partial thromboplastin time, patients more frequently have problems with thrombosis than bleeding, unless there is a coexistent prothrombin deficiency or thrombocytopenia. We report the cases of three children with the lupus anticoagulant. Two children had associated thromboses. One had a thrombosis of the iliofemoral system and the other had a partial Budd-Chiari syndrome, a thrombosis of the deep calf veins and ureteric obstruction. The third child had a concomitant prothrombin deficiency and bleeding after tooth extraction. Associated findings in these patients included a positive antinuclear antibody test in two, a positive anti-DNA antibody test in two, a false-positive VDRL test in two, and an antiphospholipid antibody test in two. PMID:6439032

  10. Gold nanoparticles in the engineering of antibacterial and anticoagulant surfaces.

    PubMed

    Ehmann, Heike M A; Breitwieser, Doris; Winter, Sascha; Gspan, Christian; Koraimann, Günther; Maver, Uros; Sega, Marija; Köstler, Stefan; Stana-Kleinschek, Karin; Spirk, Stefan; Ribitsch, Volker

    2015-03-01

    Simultaneous antibacterial and anticoagulant surfaces have been prepared by immobilization of engineered gold nanoparticles onto different kinds of surfaces. The gold nanoparticle core is surrounded by a hemocompatible, anticoagulant polysaccharide, 6-O chitosan sulfate, which serves as reduction and stabilizing agent for the generation of gold nanoparticles in a microwave mediated reaction. The particle suspension shows anticoagulant activity, which is investigated by aPTT and PT testing on citrated blood samples of three patients suffering from congenital or acquired bleeding disorders. The amount of nanoparticles deposited on the surfaces is quantified by a quartz crystal microbalance with dissipation unit. All gold containing surfaces exhibit excellent antimicrobial properties against the chosen model organism, Escherichia coli MG 1655 [R1-16]. Moreover, blood plasma coagulation times of the surfaces are increased after deposition of the engineered nanoparticles as demonstrated by QCM-D.

  11. Efficiency of three anti-coagulant rodenticides on commensal rodents.

    PubMed

    Mikhail, M W; Kamilia; Allam, A M; Soliman, M I

    2007-08-01

    Susceptibiliy level to bromadilone, difencoum and coumtertraly anticoagulants were studied in different species of Norway rat Rattus norvegicus and roof rat Rattus rattus trapped from El-Qualyobia Governorate in which the anticoagulant rodenticides were used to control rodents for long periods in some rural regions at Qualyobia. Complete mortality was showed for both species and sex within a standard feeding period (6 days) indicated to be susceptible to the three anticoagulant rodenticides. The bait eaten and corresponding active ingredient showed a noticeable more intake for R. rattus than R. norvegicus for the three compounds. The time to death showed highest mean values for R. rattus comparison to R. norvegicus. Difencoum recorded highest values of time to death compare with bromadilone and coumatetralyl. PMID:17926811

  12. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  13. Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

    PubMed

    King, Nathan; Tran, Minh-Ha

    2015-10-01

    Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment

  14. Patient self management of oral anticoagulation in routine care in the UK

    PubMed Central

    McCahon, D; Murray, E T; Jowett, S; Sandhar, H S; Holder, R L; Hussain, S; O'Donoghue, B; Fitzmaurice, D A

    2007-01-01

    Background Self management of anticoagulation: a randomised trial (SMART) was the first large scale UK trial to assess clinical and cost effectiveness of patient self management (PSM) of oral anticoagulation therapy compared to routine care. SMART showed that while PSM was as clinically effective as routine care, it was not as cost effective. SMART adds to the growing body of trial data to support PSM; however there are no data on clinical effectiveness and cost of PSM in routine care. Aim To evaluate clinical effectiveness of PSM compared to routine care outside trial conditions. Methods A retrospective multicentre matched control study. 63 PSM patients from primary care in the West Midlands were matched by age and international normalised ratio (INR) target with controls. INR results were collected for the period 1 July 2003–30 June 2004. The primary outcome measure was INR control. Results 38 PSM and 40 control patients were recruited. INR percentage time in range was 70% PSM vs 64% controls. 60% PSM were having a regular clinical review, 45% were performing an internal quality control (IQC) test and 82% were performing external quality assurance (EQA) on a regular basis. Conclusion PSM outside trial conditions is as clinically effective as routine UK care. PMID:17259295

  15. In situ-crosslinkable heparin-containing poly(ethylene glycol) hydrogels for sustained anticoagulant release

    PubMed Central

    Baldwin, Aaron D.; Robinson, Karyn G.; Militar, Jaimee; Derby, Christopher D.; Kiick, Kristi L.; Akins, Robert E.

    2014-01-01

    Low molecular weight heparin (LMWH) is widely used in anticoagulation therapies and for the prevention of thrombosis. LMWH is administered by subcutaneous injection usually once or twice per day. This frequent and invasive delivery modality leads to compliance issues for individuals on prolonged therapeutic courses, particularly pediatric patients. Here, we report a long-term delivery method for LMWH via subcutaneous injection of long-lasting hydrogels. LMWH is modified with reactive maleimide groups so that it can be crosslinked into continuous networks with four-arm thiolated polyethylene glycol (PEG-SH). Maleimide-modified LMWH (Mal-LMWH) retains bioactivity as indicated by prolonged coagulation time. Hydrogels comprising PEG-SH and Mal-LMWH degrade via hydrolysis, releasing bioactive LMWH by first-order kinetics with little initial burst release. Separately dissolved Mal-LMWH and PEG-SH solutions were co-injected subcutaneously in New Zealand White rabbits. The injected solutions successfully formed hydrogels in situ and released LMWH as measured via chromogenic assays on plasma samples, with accumulation of LMWH occurring at day two and rising to near-therapeutic dose equivalency by day 5. These results demonstrate the feasibility of using LMWH-containing, crosslinked hydrogels for sustained and controlled release of anticoagulants. PMID:22615105

  16. Anticoagulation in combination with antiangiogenesis and chemotherapy for cancer patients: evidence and hypothesis.

    PubMed

    Wang, Ji; Zhu, Chengchu

    2016-01-01

    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. PMID:27536135

  17. Neuraxial and peripheral nerve blocks in patients taking anticoagulant or thromboprophylactic drugs: challenges and solutions

    PubMed Central

    Li, Jinlei; Halaszynski, Thomas

    2015-01-01

    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. PMID:26347411

  18. Anticoagulation in combination with antiangiogenesis and chemotherapy for cancer patients: evidence and hypothesis

    PubMed Central

    Wang, Ji; Zhu, Chengchu

    2016-01-01

    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. PMID:27536135

  19. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

    PubMed Central

    Peacock, W. Frank; Rafique, Zubaid; Singer, Adam J.

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

  20. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians.

    PubMed

    Peacock, W Frank; Rafique, Zubaid; Singer, Adam J

    2016-01-01

    Nonvalvular atrial fibrillation- (NVAF-) related stroke and venous thromboembolism (VTE) are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs)-dabigatran, rivaroxaban, apixaban, and edoxaban-have been developed for the prevention of stroke or systemic embolic events (SEE) in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed. PMID:27293895

  1. Development of apixaban: a novel anticoagulant for prevention of stroke in patients with atrial fibrillation.

    PubMed

    Hanna, Michael S; Mohan, Puneet; Knabb, Robert; Gupta, Elora; Frost, Charles; Lawrence, John H

    2014-11-01

    The factor Xa inhibitor apixaban is one of the novel anticoagulants to emerge as alternatives to long-standing standards of care that include low-molecular-weight heparin and warfarin. The development of apixaban reflects a strategy to optimize the clinical pharmacology profile, dosing posology, trial designs, and statistical analyses across multiple indications, and to seek alignment with global health authorities. The primary objective of dose selection was to maintain balance between efficacy and bleeding risk. Twice-daily dosing of apixaban, rather than once daily, was chosen to lower peak concentrations and reduce fluctuations between peak and trough levels. Our discussion here focuses on the use of apixaban for stroke prevention in nonvalvular atrial fibrillation (NVAF). Supporting this indication, a pair of registrational trials was conducted that enrolled the full spectrum of patients who, by guidelines, were eligible for anticoagulation. In the AVERROES study of patients who were unsuitable for warfarin therapy, apixaban was superior to aspirin in reducing the risk of stroke or systemic embolism (SSE), without a significant increase in major bleeding (MB). In the ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) study, apixaban was superior to warfarin on the rates of SSE, MB, and all-cause mortality. Overall, these studies have demonstrated a substantially favorable benefit-risk profile for apixaban over warfarin and aspirin in NVAF. PMID:25377080

  2. How we treat bleeding associated with direct oral anticoagulants

    PubMed Central

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Liumbruno, Giancarlo M.; Franchini, Massimo

    2016-01-01

    Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect. PMID:27136433

  3. How we treat bleeding associated with direct oral anticoagulants.

    PubMed

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Liumbruno, Giancarlo M; Franchini, Massimo

    2016-09-01

    Direct oral anticoagulants are at least as effective as vitamin K antagonists for the prevention and treatment of thromboembolism. Unfortunately, differently from vitamin K antagonists, they have the great drawback of lacking specific antidotes in the case of bleeding or emergency situations such as trauma, stroke requiring thrombolysis, and urgent surgery. The progressive development of antidotes for these new drugs, which, it is hoped, will become available in the near future, will allow better and safer management of the rapid reversal of their anticoagulant effect. PMID:27136433

  4. [Why, when and how to monitor new oral anticoagulants].

    PubMed

    Tamigniau, Anne; Douxfils, Jonathan; Nicolas, Jean-Baptiste; Devalet, Bérangère; Larock, Anne-Sophie; Spinewine, Anne; Dincq, Anne-Sophie; Lessire, Sarah; Gourdin, Maximilien; Watelet, Jean-Baptiste; Mathieux, Valerie; Chatelain, Christian; Dogné, Jean-Michel; Chatelain, Bernard; Mullier, François

    2014-02-01

    Several direct oral anticoagulants (DOACs) are now widely used in the prevention and treatment of thromboembolic events. Unlike vitamin K antagonists, DOACs exhibit predictable pharmacokinetics and pharmacodynamics. DOACs are to be administered at fixed doses without routine coagulation monitoring. However, in some patient populations or specific clinical circumstances, measurement of drug exposure may be useful, such as in suspected overdose, in patients with a haemorrhagic or thromboembolic event during treatment with an anticoagulant, in those with acute renal failure, or in patients who require urgent surgery. This article provides practical guidance on laboratory testing of DOACs in routine practice and summarizes the influence of DOACs on commonly used coagulation assays. PMID:24624625

  5. Quick reference guide to the new oral anticoagulants.

    PubMed

    Hurst, Katherine; Lee, Regent; Handa, Ashok

    2016-06-01

    After the commissioning of new oral anticoagulants for the treatment and prevention of thrombosis, these medications are now widely used within clinical settings. Increasing numbers of patients present to the health services on anticoagulant medications, and it is therefore imperative for surgeons to be aware of the new therapeutic treatments available and how patients will benefit from such interventions. This review highlights the most pertinent learning points for surgeons regarding the indications, pharmacokinetics, and perioperative management of these new oral medications, as a quick reference guide. PMID:27113315

  6. Use of Direct Oral Anticoagulants in Special Populations.

    PubMed

    Li, Ang; Lopes, Renato D; Garcia, David A

    2016-10-01

    Direct oral anticoagulants (DOACs) have been approved for the treatment of venous thromboembolism and atrial fibrillation based on randomized controlled trials (RCTs) of direct comparisons with vitamin K antagonists. Despite having more than 100,000 patients enrolled, safety and efficacy are debated in selected populations. Although DOACs are reviewed as a class of anticoagulant, pharmacokinetic differences exist such that different medications may be beneficial in distinct clinical settings. Synthesizing available evidence based on phase III RCTs, post hoc subgroup analyses, and pooled metaanalyses, this review provides an overview of DOACs and scrutinizes individual differences in their applications for the special populations. PMID:27637307

  7. 21st century twist on Cullen's sign: new generation anticoagulants and splenic traum.

    PubMed

    Bilkhu, Amarvir; Mosley, Frances; Gokhale, Jay A

    2016-01-01

    New anticoagulants such as Rivaroxaban have become a popular choice for patients needing anticoagulation for atrial fibrillation or venous thromboembolism, chiefly because anticoagulation is maintained without the need for monitoring. This can be problematic in cases of trauma, and in this article, we discuss the management and outcome of managing an elderly patient with a shattered spleen while on Rivaroxaban. PMID:27511911

  8. 21st century twist on Cullen's sign: new generation anticoagulants and splenic traum

    PubMed Central

    Bilkhu, Amarvir; Mosley, Frances; Gokhale, Jay A.

    2016-01-01

    New anticoagulants such as Rivaroxaban have become a popular choice for patients needing anticoagulation for atrial fibrillation or venous thromboembolism, chiefly because anticoagulation is maintained without the need for monitoring. This can be problematic in cases of trauma, and in this article, we discuss the management and outcome of managing an elderly patient with a shattered spleen while on Rivaroxaban. PMID:27511911

  9. Recommended Therapeutic INR Range for Patients with Antiphospholipid Syndrome on Warfarin Anticoagulation: Is Moderate-Intensity (INR 2.0 - 3.0) or High-Intensity (INR 3.1 - 4.0) Better for Reducing Risk of Recurrent Thromboembolic Events?

    PubMed Central

    Do, Tiffanie; Peacock, Katie; Takundwa, Prisca T

    2016-01-01

    Patients with antiphospholipid syndrome (APS) are at increased risk of recurrent thromboembolic events due to the pathology of the disease. While prolonged anticoagulation is the treatment of choice for patients with thrombosis, much debate remains about the optimum intensity of anticoagulation. Anticoagulation with warfarin has been shown to decrease rates of thrombosis recurrence, but definitive evidence regarding targeted therapy to an INR of moderate (2.0 - 3.0) or high (3.1 - 4.0) intensity is lacking.  PMID:27725921

  10. Economic evaluation of the use of point-of-care devices in patients with long term oral anticoagulation.

    PubMed

    Gerkens, Sophie; Gailly, Jeannine; Obyn, Caroline; Devriese, Stephan; Cleemput, Irina

    2012-10-01

    To examine the cost and cost-effectiveness of the use of point-of-care (POC) devices by the general practitioner (GP), in anticoagulation clinic or by the patient in self-testing (PST) and self-management (PSM), compared with standard laboratory testing to realize international normalized ratio tests for patients on long term anticoagulation therapy. An economic evaluation was performed from the Belgian health care payer's perspective using a Markov model. Outcomes data were derived from a meta-analysis and cost data were derived from claims databases. Several scenarios were tested based on number of tests and GP's contacts and probabilistic sensitivity analysis was used to handle uncertainty. Evidence on the impact of POC on mortality was only found for PSM. Therefore, a cost-effectiveness analysis was performed for PSM and for other strategies, only a cost comparison was done. With an unchanged number of tests, POC is cost-saving compared to laboratory testing (probability > 70%). In scenarios where POC induces more tests, results were different: with 52 tests/year, only PSM kept a probability of remaining cost-saving superior to 50%. Except in the case of 100% of GP consultations maintained and 52 tests/year performed, PSM resulted in significantly more "life years gained" (LYG) than usual care and was on average cost-saving. The organisation of long term oral anticoagulation monitoring should be directed towards PSM and, to a lesser extent, PST for selected and trained patients. PMID:22437654

  11. Quantitative Systems Pharmacology Model to Predict the Effects of Commonly Used Anticoagulants on the Human Coagulation Network

    PubMed Central

    Hartmann, S; Biliouris, K; Lesko, LJ; Nowak‐Göttl, U

    2016-01-01

    Warfarin is the anticoagulant of choice for venous thromboembolism (VTE) treatment, although its suppression of the endogenous clot‐dissolution complex APC:PS may ultimately lead to longer time‐to‐clot dissolution profiles, resulting in increased risk of re‐thrombosis. This detrimental effect might not occur during VTE treatment using other anticoagulants, such as rivaroxaban or enoxaparin, given their different mechanisms of action within the coagulation network. A quantitative systems pharmacology model was developed describing the coagulation network to monitor clotting factor levels under warfarin, enoxaparin, and rivaroxaban treatment. The model allowed for estimation of all factor rate constants and production rates. Predictions of individual coagulation factor time courses under steady‐state warfarin, enoxaparin, and rivaroxaban treatment reflected the suppression of protein C and protein S under warfarin compared to rivaroxaban and enoxaparin. The model may be used as a tool during clinical practice to predict effects of anticoagulants on individual clotting factor time courses and optimize antithrombotic therapy. PMID:27647667

  12. Oral anticoagulants in coronary heart disease (Section IV). Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease.

    PubMed

    De Caterina, Raffaele; Husted, Steen; Wallentin, Lars; Andreotti, Felicita; Arnesen, Harald; Bachmann, Fedor; Baigent, Colin; Collet, Jean-Philippe; Halvorsen, Sigrun; Huber, Kurt; Jespersen, Jørgen; Kristensen, Steen Dalby; Lip, Gregory Y H; Morais, João; Rasmussen, Lars Hvilsted; Ricci, Fabrizio; Sibbing, Dirk; Siegbahn, Agneta; Storey, Robert F; Ten Berg, Jurriën; Verheugt, Freek W A; Weitz, Jeffrey I

    2016-04-01

    Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice. PMID:26952877

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

    PubMed Central

    Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar

    2016-01-01

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

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

    PubMed Central

    Vora, Pareen; Soriano-Gabarró, Montse; Suzart, Kiliana; Persson Brobert, Gunnar

    2016-01-01

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

  15. Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity

    PubMed Central

    Lei, Liang; Xue, Yong-bo; Liu, Zhong; Peng, Si-si; He, Yan; Zhang, Yang; Fang, Rong; Wang, Jian-ping; Luo, Zeng-wei; Yao, Guang-min; Zhang, Jin-wen; Zhang, Geng; Song, Hong-ping; Zhang, Yong-hui

    2015-01-01

    Coumarin derivatives are an important class of C6–C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4–8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting. PMID:26315062

  16. New oral anticoagulants for patients with nonvalvular atrial fibrillation.

    PubMed

    Holden, Amber; Azimi, Nassir; Forest, Christopher P

    2015-11-01

    Four new oral anticoagulants have been approved for reducing stroke risk in patients with nonvalvular atrial fibrillation. Compared with warfarin, these agents offer a more predictable dose response with fewer food and drug interactions and no regular blood monitoring, although some of the drugs have an increased risk of major gastrointestinal bleeding. This article reviews the new drugs.

  17. Anticoagulant activity of some Artemisia dracunculus leaf extracts

    PubMed Central

    Duric, Kemal; Kovac-Besovic, Elvira E.; Niksic, Haris; Muratovic, Samija; Sofic, Emin

    2015-01-01

    Platelet hyperactivity and platelet interaction with endothelial cells contribute to the development and progression of many cardiovascular diseases such as atherosclerosis and thrombosis. The impact of platelet activity with different pharmacological agents, such as acetylsalicylic acid and coumarin derivatives, has been shown to be effective in the prevention of cardiovascular disease. Artemisia dracunculus, L. Asteraceae (Tarragon) is used for centuries in the daily diet in many Middle Eastern countries, and it is well known for its anticoagulant activity. The present study investigates the presence of coumarins in tarragon leaves and subsequently determines the extract with a major amount of coumarin derivatives. The solvents of different polarities and different pH values were used for the purpose of purifying the primary extract in order to obtain fractions with the highest coumarin content. Those extracts and fractions were investigated for their anticoagulant activity by determining prothrombin time (PT) and the international normalized ratio (INR), expressed in relation to the coagulation time of the healthy person. Purified extracts and fractions obtained from plant residue after essential oil distillation, concentrated in coumarin derivatives, showed the best anticoagulant activity, using samples of human blood. INR maximum value (2.34) and consequently the best anticoagulant activity showed the methanol extract at concentration of 5%. The INR value of normal plasma in testing this extract was 1.05. PMID:26042507

  18. Can the anticoagulant effects of dabigatran be reversed?

    PubMed

    Bickley, Aida Rebecca; Wallace, Caleb

    2016-09-01

    Idarucizumab is a humanized monoclonal antibody fragment for reversal of the anticoagulant effects of dabigatran. This drug can be used for patients who need emergency surgery or invasive procedures, as well as those with life-threatening or uncontrolled bleeding. PMID:27575900

  19. Qualitative identification of rodenticide anticoagulants by LC-MS/MS.

    PubMed

    Middleberg, Robert A; Homan, Joseph

    2012-01-01

    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

  20. [New anticoagulants for stroke prevention in atrial fibrillation].

    PubMed

    Diener, H C; Hajjar, K; Frank, B; Perrey, M

    2012-06-01

    Oral anticoagulation with vitamin K antagonists (warfarin, phenprocoumon) is successful in both primary and secondary stroke prevention for patients with atrial fibrillation (AF), yielding a 60-70% relative reduction in stroke risk compared with placebo and a mortality reduction of 26%. However, these agents have a number of well documented shortcomings. This review describes the current landscape and developments in stroke prevention in patients with AF with special reference to secondary prevention. A number of new drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists are under investigation. These include direct factor Xa inhibitors and direct thrombin inhibitors. Recent studies (RE-LY, ROCKET-AF, AVERROES, ARISTOTLE) provide promising results for these new agents including higher efficacy and significantly lower incidences of intracranial bleeding compared with warfarin. The new substances show similar results in secondary as well as in primary stroke prevention in patients with AF. The new anticoagulants add to the therapeutic options for patients with AF and offer a number of advantages over warfarin for both clinician and patient, including a favorable bleeding profile and convenience of use. Consideration of these new anticoagulants will improve clinical decision-making. PMID:22539096

  1. Novel Oral Anticoagulant Use Among Patients with Atrial Fibrillation Hospitalized with Ischemic Stroke or Transient Ischemic Attack

    PubMed Central

    Patel, Priyesh A.; Zhao, Xin; Fonarow, Gregg C.; Lytle, Barbara L.; Smith, Eric E.; Xian, Ying; Bhatt, Deepak L.; Peterson, Eric D.; Schwamm, Lee H.; Hernandez, Adrian F.

    2015-01-01

    Background Novel oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for preventing stroke or transient ischemic attack (TIA) in patients with atrial fibrillation (AF), yet diffusion of these therapies and patterns of use among AF patients with ischemic stroke and TIA have not been well characterized. Methods and Results Using data from Get With The Guidelines®–Stroke, we identified a cohort of 61,655 AF patients with ischemic stroke or TIA hospitalized between 10/2010–09/2012 and discharged on warfarin or NOAC (either dabigatran or rivaroxaban). Multivariable logistic regression was used to identify factors associated with NOAC versus warfarin therapy. In our study population, warfarin was prescribed to 88.9%, dabigatran to 9.6%, and rivaroxaban to 1.5%. NOAC use increased from 0.04% to a 16–17% plateau during the study period, though anticoagulation rates among eligible patients did not change appreciably (93.7% vs. 94.1% from first quarter 2011 to second quarter 2012), suggesting a trend of switching from warfarin to NOACs rather than increased rates of anticoagulation among eligible patients. Several bleeding risk factors and CHA2DS2-VASc scores were lower among those discharged on NOAC versus warfarin therapy (47.9% vs. 40.9% with CHA2DS2-VASc ≤5, p<0.001 for difference in CHA2DS2-VASc). Conclusions NOACs have had modest but growing uptake over time among AF patients hospitalized with stroke or TIA and are prescribed to patients with lower stroke risk compared to warfarin. PMID:26058721

  2. [Anticoagulation and platelet inhibition - dosing recommendations at the beginning and the end of treatment].

    PubMed

    Ivandic, Boris T; Zankl, Alexandra; Katus, Hugo A

    2008-10-01

    Anticoagulants and anti-platelet drugs are essential and widely used therapeutic tools in modern cardiovascular medicine. However, the initiation of anti-thrombotic therapies, their termination, or transient discontinuation (e.g. for surgical procedures) are critical steps which have to be managed appropriately. In the near future, several novel irreversibly or reversibly acting anti-thrombotic drugs with direct and indirect mechanisms of action, will be approved. Their prescription will require a deep understanding of their pharmacodynamics and -kinetics. In addition, pharmacogenomic issues will become increasingly important for the optimization of individual therapeutic strategies. This review summarizes clinically relevant principles and discusses them in the light of the assessment of the individual thrombotic and bleeding risks.

  3. A study of the safety of continued anticoagulation for cataract surgery patients.

    PubMed

    Hirschman, Don R; Morby, Lesa J

    2006-01-01

    Cataract surgery is the most common procedure performed on Medicare recipients. Many of these patients have been on anticoagulation therapy (ACT) regimens, but no consistent standard currently governs the use or cessation of ACT prior to surgery. This study evaluated the safety of continuing ACT in cataract surgery patients (of ASA III physical status) at seven centers. There was a 53% incidence of previous ACT among the 1,842 individuals sampled. During 2,241 procedures, only two patients (one on ACT) experienced abnormal surgical bleeding, noted as hyphemas. Seventeen (0.9%), nine on ACT and eight not on it, had some type of bleeding related to regional anesthesia; of these, nine had bruising and eight had subconjunctival hemorrhage. No major complications were noted in the ACT group during surgery, or at visits 1 day and 1 week postoperatively.

  4. Relationship between anticoagulant activities and polyanionic properties of rabbit thrombomodulin.

    PubMed

    Bourin, M C; Ohlin, A K; Lane, D A; Stenflo, J; Lindahl, U

    1988-06-15

    Rabbit thrombomodulin displays three distinct blood anticoagulant activities: it promotes the activation of protein C by thrombin (protein C activation cofactor activity); it promotes the inactivation of thrombin by thrombin (direct anticoagulant activity). The effects on these activities of mouse anti-thrombomodulin monoclonal antibodies and of the heparin-neutralizing proteins, platelet factor 4, histidine-rich glycoprotein, and S-protein, were investigated. One of the antibodies, which did not influence the functional properties of thrombomodulin, was used as an immunoaffinity ligand for purification of the protein. Two other antibodies, which were found to abrogate the protein C activation cofactor activity of the purified thrombomodulin, also abolished the antithrombin-dependent and the direct anticoagulant activities. The heparin-neutralizing proteins all inhibited the two latter activities, albeit to a varying extent, but did not appreciably affect the activation of protein C. These results are interpreted in relation to our previous finding that rabbit thrombomodulin contains an acidic domain, tentatively identified as a sulfated glycosaminoglycan (Bourin, M.-C., Boffa, M.-C., Björk, I., and Lindahl, U. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5924-5928). It is proposed that the acidic domain interacts with thrombin at the protein C activation site and that this interaction is a prerequisite to the expression of direct as well as antithrombin-dependent anticoagulant activity. The interaction is not essential to, but compatible with, the activation of protein C. Experiments involving treatment of thrombomodulin with various glycanases or with nitrous acid, followed by measurement of anticoagulant activities, indicated that the acidic domain is constituted by a sulfated galactosaminoglycan and not by a heparin-related polysaccharide as previously suggested.

  5. Serpin-independent anticoagulant activity of a fucosylated chondroitin sulfate.

    PubMed

    Glauser, Bianca F; Pereira, Mariana S; Monteiro, Robson Q; Mourão, Paulo A S

    2008-09-01

    Fucosylated chondroitin sulfate is a glycosaminoglycan from sea cucumber composed of a chondroitin sulfate-like core with branches of sulfated fucose. This glycosaminoglycan has high anticoagulant and antithrombotic activities. Its serpin-dependent anticoagulant activity is mostly due to activating thrombin inhibition by heparin cofactor II. Here, we evaluated the anticoagulant activity of fucosylated chondroitin sulfate using antithrombin- and heparin cofactor II-free plasmas. In contrast to mammalian heparin, the invertebrate glycosaminoglycan is still able to prolong coagulation time and delay thrombin and factor Xa generation in serpin-free plasmas. These observations suggest that fucosylated chondroitin sulfate has a serpin-independent anticoagulant effect. We further investigated this effect using purified blood coagulation proteins. Clearly, fucosylated chondroitin sulfate inhibits the intrinsic tenase and prothrombinase complexes, which are critical for thrombin generation. It is possible that the invertebrate chondroitin sulfate inhibits interactions between cofactor Va and factor Xa. We also employed chemically modified polysaccharides in order to trace a structure versus activity relationship. Removal of the sulfated fucose branches, but not reduction of the glucuronic acid residues to glucose, abolished its activity. In conclusion, fucosylated chondroitin sulfate has broader effects on the coagulation system than mammalian glycosaminoglycans. In addition to its serpin-dependent inhibition of coagulation protease, it also inhibits the generation of factor Xa and thrombin by the tenase and prothrombinase complexes, respectively. In plasma systems, the serpin-independent anticoagulant effect of fucosylated chondroitin sulfate predominates over its serpin-dependent action. This glycosaminoglycan opens new avenues for the development of antithrombotic agents.

  6. A method for anticoagulation of children on mechanical circulatory support.

    PubMed

    Copeland, Hannah; Nolan, Paul E; Covington, Diane; Gustafson, Monica; Smith, Richard; Copeland, Jack G

    2011-11-01

    Anticoagulation of children on mechanical circulatory support presents a challenge. We implanted 28 devices in children and infants using a consistent anticoagulation protocol. We performed a retrospective review of all children implanted in our program with mechanical assist devices since 1997. Heparin, dipyridamole, and aspirin were used for anticoagulation and antiaggregation. Coagulation monitoring included thromboelastography (TEG), platelet aggregration studies, international normalized ratio, partial thromboplastin time, and platelet count. Twenty-eight children, ages 1 month to 16 years (mean 5.3; median 2.4 years), were implanted for 3-107 days (mean 27; median 17). Eighteen received left ventricular assist devices, seven received biventricular assist devices, and three received total artificial hearts. Adverse events during the 720 days of device support included the following: six (21%) reoperations for bleeding; seven strokes (25%): two fatal, two with a mild residual deficit, and three without deficit; and three (11%) visceral emboli: two fatal and one nonfatal. There were eight deaths (29%). Causes of death were embolic (four), graft failure post-transplantation (one), preimplant anoxic brain damage (two), and postexplant heart failure (one). 24/28 (86%) survived to transplantation or weaning from device and 20/28 (71%) were discharged from the hospital, 10 after transplantation and 10 after native heart recovery. All 20 early survivors survived long term. We describe an anticoagulation protocol based upon TEG and platelet aggregation studies and using heparin, aspirin, and dipyridamole. Adequate anticoagulation is more difficult in children. However, 71% of the patients in our study survived long term.

  7. Guidance for the practical management of warfarin therapy in the treatment of venous thromboembolism.

    PubMed

    Witt, Daniel M; Clark, Nathan P; Kaatz, Scott; Schnurr, Terri; Ansell, Jack E

    2016-01-01

    Venous thromboembolism (VTE) is a serious and often fatal medical condition with an increasing incidence. The treatment of VTE is undergoing tremendous changes with the introduction of the new direct oral anticoagulants and clinicians need to understand new treatment paradigms. This article, initiated by the Anticoagulation Forum, provides clinical guidance based on existing guidelines and consensus expert opinion where guidelines are lacking. Well-managed warfarin therapy remains an important anticoagulant option and it is hoped that anticoagulation providers will find the guidance contained in this article increases their ability to achieve optimal outcomes for their patients with VTE Pivotal practical questions pertaining to this topic were developed by consensus of the authors and were derived from evidence-based consensus statements whenever possible. The medical literature was reviewed and summarized using guidance statements that reflect the consensus opinion(s) of all authors and the endorsement of the Anticoagulation Forum's Board of Directors. In an effort to provide practical and implementable information about VTE and its treatment, guidance statements pertaining to choosing good candidates for warfarin therapy, warfarin initiation, optimizing warfarin control, invasive procedure management, excessive anticoagulation, subtherapeutic anticoagulation, drug interactions, switching between anticoagulants, and care transitions are provided. PMID:26780746

  8. Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation.

    PubMed

    Ortel, Thomas L

    2009-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT. PMID:20008202

  9. Cognitive function and adherence to anticoagulation treatment in patients with atrial fibrillation

    PubMed Central

    Jankowska-Polańska, Beata; Katarzyna, Lomper; Lidia, Alberska; Joanna, Jaroch; Dudek, Krzysztof; Izabella, Uchmanowicz

    2016-01-01

    Background Medication adherence is an integral part of the comprehensive care of patients with atrial fibrillation (AF) receiving oral anticoagulations (OACs) therapy. Many patients with AF are elderly and may suffer from some form of cognitive impairment. This study was conducted to investigate whether cognitive impairment affects the level of adherence to anticoagulation treatment in AF patients. Methods The study involved 111 AF patients (mean age, 73.5 ± 8.3 years) treated with OACs. Cognitive function was assessed using the Mini Mental State Examination (MMSE). The level of adherence was assessed by the 8-item Morisky Medication Adherence Scale (MMAS-8). Scores on the MMAS-8 range from 0 to 8, with scores < 6 reflecting low adherence, 6 to < 8 medium adherence, and 8 high adherence. Results 46.9% of AF patients had low adherence, 18.8% had moderate adherence, and 33.3% had high adherence to OACs. Patients with lower adherence were older than those with moderate or high adherence (76.6 ± 8.7 vs. 71.3 ± 6.4 vs. 71.1 ± 6.7 years) and obtained low MMSE scores, indicating cognitive disorders or dementia (MMSE = 22.3 ± 4.2). Patients with moderate or high adherence obtained high MMSE test results (27.5 ± 1.7 and 27.5 ± 3.6). According to Spearman's rank correlation, worse adherence to treatment with OACs was determined by older age (rS = −0.372) and lower MMSE scores (rS = 0.717). According to multivariate regression analysis, the level of cognitive function was a significant independent predictor of adherence (b = 1.139). Conclusions Cognitive impairment is an independent determinant of compliance with pharmacological therapy in elderly patients with AF. Lower adherence, beyond the assessment of cognitive function, is related to the age of patients. PMID:27605935

  10. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications: guidelines from the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain.

    PubMed

    Narouze, Samer; Benzon, Honorio T; Provenzano, David A; Buvanendran, Asokumar; De Andres, José; Deer, Timothy R; Rauck, Richard; Huntoon, Marc A

    2015-01-01

    Interventional spine and pain procedures cover a far broader spectrum than those for regional anesthesia, reflecting diverse targets and goals. When surveyed, interventional pain and spine physicians attending the American Society of Regional Anesthesia and Pain Medicine (ASRA) 11th Annual Pain Medicine Meeting exhorted that existing ASRA guidelines for regional anesthesia in patients on antiplatelet and anticoagulant medications were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors necessitated separate guidelines for pain and spine procedures. In response, ASRA formed a guidelines committee. After preliminary review of published complication reports and studies, committee members stratified interventional spine and pain procedures according to potential bleeding risk as low-, intermediate-, and high-risk procedures. The ASRA guidelines were deemed largely appropriate for the low- and intermediate-risk categories, but it was agreed that the high-risk targets required an intensive look at issues specific to patient safety and optimal outcomes in pain medicine. The latest evidence was sought through extensive database search strategies and the recommendations were evidence-based when available and pharmacology-driven otherwise. We could not provide strength and grading of these recommendations as there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations.

  11. Anticoagulation for three versus six months in patients with deep vein thrombosis or pulmonary embolism, or both: randomised trial

    PubMed Central

    Bentley, D P; Prescott, R J; Routledge, P A; Shetty, H G M; Williamson, I J

    2007-01-01

    Objective To determine the optimum duration of oral anticoagulant therapy after an episode of deep vein thrombosis or pulmonary embolism, or both. Design Multicentre, prospective, randomised study with follow-up for one year. Setting 46 hospitals in United Kingdom. Participants Patients aged ≥18 with deep vein thrombosis or pulmonary embolism, or both. Interventions Three (n=369) or six months (n=380) of anticoagulation with heparin for five days accompanied and followed by warfarin, with a target international normalised ratio of 2.0-3.5. Main outcome measures Death from deep vein thrombosis or pulmonary embolism; failure to resolve, extension, recurrence of during treatment; recurrence after treatment; and major haemorrhage during treatment. Results In the patients allocated to three months' treatment two died from deep vein thrombosis or pulmonary embolism during or after treatment, compared with three in the six month group. During treatment deep vein thrombosis or pulmonary embolism failed to resolve, extended, or recurred in six patients in the three month group without fatal consequences, compared with 10 in the six month group. After treatment there were 23 non-fatal recurrences in the three month group and 16 in the six month group. Fatal and non-fatal deep vein thrombosis or pulmonary embolism during treatment, and after treatment thus occurred in 31(8%) of those who had received three months' anticoagulation compared with 29 (8%) of those who had received six months' (P=0.80, 95% confidence interval for difference −3.1% to 4.7%). There were no fatal haemorrhages during treatment but there were eight major haemorrhages in those treated for six months and none in those treated for three months (P=0.008, −3.5% to −0.7%). Thus 31 (8%) of the patients receiving three months' anticoagulation experienced adverse outcomes as a result of deep vein thrombosis or pulmonary embolism or its treatment compared with 35 (9%) of those receiving six months' (P=0

  12. Direct vitamin k antagonist anticoagulant treatment health care costs in patients with non-valvular atrial fibrillation

    PubMed Central

    2014-01-01

    Background There is evidence suggesting that most thromboembolic complications could be prevented with adequate pharmacological anticoagulation. We estimated the direct health care costs of anticoagulant treatment with oral vitamin K antagonists in patients diagnosed with non-valvular atrial fibrillation. Methods This observational study examined the clinical records of patients diagnosed with non-valvular atrial fibrillation who received anticoagulant treatment with oral vitamin K antagonists. Data from clinical records were used in the study: international normalized ratio, number of monitoring visits, type of anticoagulant, hospital admissions from complications, and concomitant medication. Drug cost was calculated based on the official Spanish Ministry of Health price list. Monitoring expenses were included the cost of the medical supplies used in the procedures. Hospitalization costs were calculated using the Diagnosis Related Group price for each case. Hospital visits costs were calculated by one of four different scenarios, using either the invoice rates for the regional health care authority or cost per visit as established by analytical accounting methods. Results We collected data from 1,257 patients diagnosed with non-valvular atrial fibrillation who were receiving oral anticoagulant therapy. Depending on the scheme used, the direct health care costs for these patients ranged from €423,695 - €1,436,038 per annum. The average cost per patient varied between €392 - €1,341, depending on the approach used. Patients with international normalized ratio values within the therapeutic range on 25% of their visits represented an average cost between €441.70 - €1,592. Those within the therapeutic range on 25%–50% of visits had associated costs of €512.37 - €1,703.91. When international normalized ratio values were within the therapeutic range on 50% - 75% of the visits, the costs ranged between €400.80- €1,375.74. The

  13. In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

    2011-05-01

    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.

  14. Is Anticoagulation Discontinuation Achievable with Citrate Dialysate during HDF Sessions?

    PubMed Central

    Oger, Emmanuel; Hamel, Didier; Lombart, Marie-Laure; Hermès, Isabelle

    2016-01-01

    Citrate dialysate has been developed for few years to replace acetate and HCl concentrates. In Online Postdilution Hemodiafiltration (OL-POST-HDF), several issues are remaining concerning the possibility of stopping anticoagulation during sessions and the side effects of citrate solutions on calcium metabolism. This 1-year monocentric retrospective study included all patients exposed to citrate in OL-POST-HDF with nadroparin decrease for more than one month. Clotting events, serum calcium, PTH, hemoglobin, CRP, depuration parameters, and treatments administrated were recorded for analysis. 27 patients experienced nadroparin decrease and 5 did not receive nadroparin at the end of the study. Nadroparin decrease and withdrawal were both associated with more clotting events whereas the use of vitamin K antagonists was protective. No significant metabolic side effects were observed. Citrate dialysate does not allow anticoagulation discontinuation or decrease but has no significant side effects on mineral bone metabolism or erythropoiesis. PMID:27803814

  15. Drug Interactions of Direct-Acting Oral Anticoagulants.

    PubMed

    Fitzgerald, John Leonard; Howes, Laurence Guy

    2016-09-01

    In recent years, new direct-acting oral anticoagulants (DOACs) have been introduced into clinical practice that specifically inhibit either factor Ia or Xa. These drugs have, to a large extent, replaced warfarin for the treatment of venous thrombosis, pulmonary embolism, and non-valvular atrial fibrillation. They have potential advantages over warfarin in providing more stable anticoagulation and the lack of a need for regular venesection to monitor activity. They also have the promise of less drug and food interactions. All of these drugs are substrates for the permeability glycoprotein (P-gp) excretion system, and several are metabolised, in part, by cytochrome P450 (CYP) 3A4. This current article assesses the interactions that do or may occur with the DOACs, particularly with respect to the P-gp and CYP3A4 systems. PMID:27435452

  16. The enhanced anticoagulation for graphene induced by COOH(+) ion implantation.

    PubMed

    Liu, Xiaoqi; Cao, Ye; Zhao, Mengli; Deng, Jianhua; Li, Xifei; Li, Dejun

    2015-01-01

    Graphene may have attractive properties for some biomedical applications, but its potential adverse biological effects, in particular, possible modulation when it comes in contact with blood, require further investigation. Little is known about the influence of exposure to COOH(+)-implanted graphene (COOH(+)/graphene) interacting with red blood cells and platelets. In this paper, COOH(+)/graphene was prepared by modified Hummers' method and implanted by COOH(+) ions. The structure and surface chemical and physical properties of COOH(+)/graphene were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle measurement. Systematic evaluation of anticoagulation, including in vitro platelet adhesion assays and hemolytic assays, proved that COOH(+)/graphene has significant anticoagulation. In addition, at the dose of 5 × 10(17) ions/cm(2), COOH(+)/graphene responded best on platelet adhesion, aggregation, and platelet activation.

  17. Coagulant and anticoagulant activities in Jatropha curcas latex.

    PubMed

    Osoniyi, Omolaja; Onajobi, Funmi

    2003-11-01

    Jatropha curcas Linn. (Euphorbiaceae), a medicinal plant commonly grown in the Tropics, is traditionally used as a haemostatic. Investigation of the coagulant activity of the latex of Jatropha curcas showed that whole latex significantly (P<0.01) reduced the clotting time of human blood. Diluted latex, however, prolonged the clotting time: at high dilutions, the blood did not clot at all. This indicates that Jatropha curcas latex possesses both procoagulant and anticoagulant activities. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests on plasma confirm these observations. Solvent partitioning of the latex with ethyl acetate and butanol led to a partial separation of the two opposing activities: at low concentrations, the ethyl acetate fraction exhibited a procoagulant activity, while the butanol fraction had the highest anticoagulant activity. The residual aqueous fraction had no significant effect on the clotting time of blood and the PT but slightly prolonged the APTT.

  18. [Anticoagulant activity of coumarins from Ferula communis L].

    PubMed

    Lamnaouer, D

    1999-01-01

    Ferula communis is an ombelliferous plant of the Mediterranean regions. It is represented in Morocco by two varieties: brevifolia and genuina. The later is very rich in a soap or resinous gum. This product, collected from the roots, is largely used in traditional medicine. It is know as fessoukh in Morocco and other Arab countries. This plant is also well known for its toxicity and its anticoagulant activity. In the present review, are discussed: (1) the ethnobotany of the plant, especially medicinal uses of fessoukh in traditional medicine as well as alimentary use of young stems as legumes; (2) clinical and biochemical data of intoxication by this plant, which are dominated by haemorrhage as a consequence of blood coagulation disturbance; (3) 4-hydroxycoumarins isolated from Ferula communis L. and their anticoagulant activity; (4) the role of vitamin K1 in the treatment of poisoning by this plant.

  19. New anticoagulant and antiplatelet agents: a primer for the gastroenterologist.

    PubMed

    Baron, Todd H; Kamath, Patrick S; McBane, Robert D

    2014-02-01

    A large number of patients worldwide receive anticoagulant and antiplatelet agents, collectively known as antithrombotic agents. Several new anticoagulants and antiplatelet agents recently were approved for use. Gastroenterologists may be unfamiliar with the mechanism of action, indications for use, and pharmacokinetics of these newer drugs. In patients undergoing elective and urgent endoscopic procedures, clinicians must be familiar with these medications to optimize outcomes. When the decision is made to continue the newer antithrombotic agents for elective procedures, the clinician must understand the risk that these agents may impart on procedural-induced bleeding. Finally, it is important to understand how to manage these agents in the presence of acute gastrointestinal bleeding. In this article the use of newer antithrombotic agents is reviewed. PMID:23735447

  20. Evaluation of anticoagulant activity of two algal polysaccharides.

    PubMed

    Faggio, C; Pagano, M; Dottore, A; Genovese, G; Morabito, M

    2016-09-01

    Marine algae are important sources of phycocolloids like agar, carrageenans and alginates used in industrial applications. Algal polysaccharides have emerged as an important class of bioactive products showing interesting properties. The aim of our study was to evaluate the potential uses as anticoagulant drugs of algal sulphate polysaccharides extracted from Ulva fasciata (Chlorophyta) and Agardhiella subulata (Rhodophyta) collected in Ganzirri Lake (Cape Peloro Lagoon, north-eastern Sicily, Italy). Toxicity of algal extracts through trypan blue test and anticoagulant action measured by activated partial thromboplastin time (APTT), prothrombin time (PT) test has been evaluated. Algal extracts showed to prolong the PT and APTT during the coagulation cascade and to avoid the blood coagulation of samples. Furthermore, the algal extracts lack toxic effects towards cellular metabolism and their productions are relatively at low cost. This permits to consider the algae as the biological source of the future.

  1. Factors influencing quality of anticoagulation control and warfarin dosage in patients after aortic valve replacement within the 3 months of follow up.

    PubMed

    Wypasek, E; Mazur, P; Bochenek, M; Awsiuk, M; Grudzien, G; Plincer, D; Undas, A

    2016-06-01

    Warfarin dosage estimation using the pharmacogenetic algorithms has been shown to improve the quality of anticoagulation control in patients with atrial fibrillation. We sought to assess the genetic, demographic and clinical factors that determine the quality of anticoagulation in patients following aortic valve replacement (AVR). We studied 200 consecutive patients (130 men) aged 63 ± 12.3 years, undergoing AVR, in whom warfarin dose was established using a pharmacogenetic algorithm. The quality of anticoagulation within the first 3 months since surgery was expressed as the time of international normalized ratio (INR) in the therapeutic range (TTR). The median TTR in the entire cohort was 59.6% (interquartile range, 38.7 - 82.7). Ninety-nine (49.5%) patients with TTR ≥ 60% did not differ from those with poor anticoagulation control (TTR < 60%) with regard to demographic and cardiovascular risk factors. Coronary artery disease (n = 84, 42%) and previous stroke (n = 5, 2.5%) predicted higher TTR, while possession of CYP2C9*2 variant allele (n = 49, 25%) was associated with lower TTR (P = 0.01). In turn, VKORC1 c.-1639A, CYP2C9*2 and *3 variants were independently associated with actual warfarin dose (P < 0.0001). In AVR patients better anticoagulation control is observed in patients with coronary artery disease and history of stroke, which might result in part from previous lifestyle modification and therapy. Possession of CYP2C9*2 and/or CYP2C9*3 allele variants is associated with lower TTR values and warfarin dose variations in AVR patients, the latter affected also by VKORC1 c.-1693G>A polymorphism. PMID:27511999

  2. Effect of citrate anticoagulants on factor VIII levels in plasma.

    PubMed

    Rock, G; Tittley, P; Fuller, V

    1988-01-01

    The citrate anticoagulants used during blood collection have been developed for their benefits to red cells. The concentrations in which they are used are strictly regulated in the United States: citrate-phosphate-dextrose-adenine (CPDA) is used in a 1:8 ratio for the collection of whole blood, whereas 4 percent sodium citrate (NaCit) is used in a 1:10 ratio for manual plasmapheresis. Acid-citrate-dextrose formula A (ACD-A) or formula B (ACD-B) and NaCit are commonly used in a 1:12 or 1:15 ratio during automated plasmapheresis. These anticoagulants have different initial and final pH values and citrate concentrations and different effects on the recovery of factor VIII (FVIII) in the plasma. NaCit has a higher initial pH (6.64) than ACD-A (4.98), ACD-B (5.60), or CPDA (5.12). The effects of these different anticoagulants on plasma constituents obtained from six healthy subjects were studied. In standard citrate concentrations, the FVIII level was significantly lower (p less than 0.05) in the NaCit used for manual plasmapheresis than in either of the ACD solutions used in automated plasmapheresis (104 U/dl vs. 153 and 160 U/dl). When various ratios of NaCit to blood were used, the pH increased from 7.62 at a 1:10 dilution to 7.65 at a 1:50 dilution. As expected, a progressive decrease in anticoagulant level was associated with an increase in ionized calcium and also in the level of FVIII, with the latter values rising from 104 U per dl at 1:10 to 137 at 1:20 and 148 U per dl at 1:30. Clot formation was detected only at a ratio of 1:35.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. The Genetic Basis of Resistance to Anticoagulants in Rodents

    PubMed Central

    Pelz, Hans-Joachim; Rost, Simone; Hünerberg, Mirja; Fregin, Andreas; Heiberg, Ann-Charlotte; Baert, Kristof; MacNicoll, Alan D.; Prescott, Colin V.; Walker, Anne-Sophie; Oldenburg, Johannes; Müller, Clemens R.

    2005-01-01

    Anticoagulant compounds, i.e., derivatives of either 4-hydroxycoumarin (e.g., warfarin, bromadiolone) or indane-1,3-dione (e.g., diphacinone, chlorophacinone), have been in worldwide use as rodenticides for >50 years. These compounds inhibit blood coagulation by repression of the vitamin K reductase reaction (VKOR). Anticoagulant-resistant rodent populations have been reported from many countries and pose a considerable problem for pest control. Resistance is transmitted as an autosomal dominant trait although, until recently, the basic genetic mutation was unknown. Here, we report on the identification of eight different mutations in the VKORC1 gene in resistant laboratory strains of brown rats and house mice and in wild-caught brown rats from various locations in Europe with five of these mutations affecting only two amino acids (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln, Leu128Ser). By recombinant expression of VKORC1 constructs in HEK293 cells we demonstrate that mutations at Tyr139 confer resistance to warfarin at variable degrees while the other mutations, in addition, dramatically reduce VKOR activity. Our data strongly argue for at least seven independent mutation events in brown rats and two in mice. They suggest that mutations in VKORC1 are the genetic basis of anticoagulant resistance in wild populations of rodents, although the mutations alone do not explain all aspects of resistance that have been reported. We hypothesize that these mutations, apart from generating structural changes in the VKORC1 protein, may induce compensatory mechanisms to maintain blood clotting. Our findings provide the basis for a DNA-based field monitoring of anticoagulant resistance in rodents. PMID:15879509

  4. The genetic basis of resistance to anticoagulants in rodents.

    PubMed

    Pelz, Hans-Joachim; Rost, Simone; Hünerberg, Mirja; Fregin, Andreas; Heiberg, Ann-Charlotte; Baert, Kristof; MacNicoll, Alan D; Prescott, Colin V; Walker, Anne-Sophie; Oldenburg, Johannes; Müller, Clemens R

    2005-08-01

    Anticoagulant compounds, i.e., derivatives of either 4-hydroxycoumarin (e.g., warfarin, bromadiolone) or indane-1,3-dione (e.g., diphacinone, chlorophacinone), have been in worldwide use as rodenticides for >50 years. These compounds inhibit blood coagulation by repression of the vitamin K reductase reaction (VKOR). Anticoagulant-resistant rodent populations have been reported from many countries and pose a considerable problem for pest control. Resistance is transmitted as an autosomal dominant trait although, until recently, the basic genetic mutation was unknown. Here, we report on the identification of eight different mutations in the VKORC1 gene in resistant laboratory strains of brown rats and house mice and in wild-caught brown rats from various locations in Europe with five of these mutations affecting only two amino acids (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln, Leu128Ser). By recombinant expression of VKORC1 constructs in HEK293 cells we demonstrate that mutations at Tyr139 confer resistance to warfarin at variable degrees while the other mutations, in addition, dramatically reduce VKOR activity. Our data strongly argue for at least seven independent mutation events in brown rats and two in mice. They suggest that mutations in VKORC1 are the genetic basis of anticoagulant resistance in wild populations of rodents, although the mutations alone do not explain all aspects of resistance that have been reported. We hypothesize that these mutations, apart from generating structural changes in the VKORC1 protein, may induce compensatory mechanisms to maintain blood clotting. Our findings provide the basis for a DNA-based field monitoring of anticoagulant resistance in rodents. PMID:15879509

  5. [From old to new anticoagulants: the role of the biologist].

    PubMed

    Samama, Mm; Depasse, F

    2009-01-01

    Anticoagulant drugs are of great interest to patients and clinical physicians, as well as research scientists. The latter two groups combine their efforts to unravel the related mechanisms of action, as well as means of monitoring and proper dosing. Unfractionated heparin and low molecular weight heparins and vitamin K antagonists have been on board for several decades by now. They act on several clotting factors in certain sequences. Newer drugs, produced by chemical synthesis, act on a more specific target, often factor Xa or factor IIa. These newer anticoagulants have a great convenience in being orally administered and not needing routing laboratory monitoring - which is their main advantage. Hirudine and fondaparinux have been registered for a few years. This year, that is 2008 + 2009, two of these new anticoagulants have been registered and approved for use in Europe and Canada - these are dabigatran etexilate (Pradaxa) and rivaroxaban (Xarelto). Both do not require routine laboratory monitoring. However, coagulation assays for measuring their activity have been studied. A small number of standardized tests should be perfected. PMID:19789124

  6. Strategies for urgent reversal of target-specific oral anticoagulants.

    PubMed

    Davis, Estella M; Uhlmeyer, Erin M; Schmidt, David P; Schardt, Greg L

    2014-12-01

    The direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and apixaban are US Food and Drug Administration (FDA)-approved target-specific oral anticoagulants (TSOACs) that have emerged onto the market for use in some indications similar to those for warfarin; in addition, edoxaban is seeking FDA approval. Similar indications include reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation for all 3 agents, for the prevention of deep vein thrombosis that may lead to pulmonary embolism in patients undergoing hip or knee surgery for rivaroxaban and apixaban, and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. As anticoagulants, they are all associated with a risk of bleeding, and, unfortunately, there are no approved antidotes for reversal of these agents. A number of small studies in human subjects and in human/animal models exposed to TSOACs have evaluated the use of activated charcoal, hemodialysis for dabigatran, or clotting factor concentrates for their ability to neutralize the anticoagulant effects or reduce drug concentrations of TSOACs. Clotting factor concentrates that have been used include prothrombin complex concentrates and recombinant factor VII. This review examines studies and case reports evaluating these strategies for expedited or emergent reversal of TSOACs. PMID:25485923

  7. Efficacy and safety of novel anticoagulants in the elderly

    PubMed Central

    Karamichalakis, Nikolaos; Georgopoulos, Stamatis; Vlachos, Konstantinos; Liatakis, Ioannis; Efremidis, Michael; Sideris, Antonios; Letsas, Konstantinos P

    2016-01-01

    Atrial fibrillation and venous thromboembolism (VTE) are common disorders associated with maleficent thrombotic events, particularly in the elderly patients. Polypharmacy, co-morbidities, and altered pharmacokinetics, often present in these patients, render the use of anticoagulants quite challenging. Novel oral anticoagulants (NOACs) have recently emerged as alternatives to Vitamin K Antagonists (VKAs) and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety has been well-established in the general population but the balance between benefit and harm in the elderly is still unclear. Routine use in these patients is uncommon. Accumulating data have shown that the benefit of NOACs is consistent among all age groups, featuring equal or greater efficacy in preventing thrombotic events. Excess bleedings were lower with NOACs in comparison to VKAs, but bleeding patterns were disparate among them and head to head comparison is not available. The present review highlights on the efficacy and safety of novel anticoagulants in the elderly population. PMID:27781063

  8. Strategies for urgent reversal of target-specific oral anticoagulants.

    PubMed

    Davis, Estella M; Uhlmeyer, Erin M; Schmidt, David P; Schardt, Greg L

    2014-12-01

    The direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and apixaban are US Food and Drug Administration (FDA)-approved target-specific oral anticoagulants (TSOACs) that have emerged onto the market for use in some indications similar to those for warfarin; in addition, edoxaban is seeking FDA approval. Similar indications include reducing the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation for all 3 agents, for the prevention of deep vein thrombosis that may lead to pulmonary embolism in patients undergoing hip or knee surgery for rivaroxaban and apixaban, and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. As anticoagulants, they are all associated with a risk of bleeding, and, unfortunately, there are no approved antidotes for reversal of these agents. A number of small studies in human subjects and in human/animal models exposed to TSOACs have evaluated the use of activated charcoal, hemodialysis for dabigatran, or clotting factor concentrates for their ability to neutralize the anticoagulant effects or reduce drug concentrations of TSOACs. Clotting factor concentrates that have been used include prothrombin complex concentrates and recombinant factor VII. This review examines studies and case reports evaluating these strategies for expedited or emergent reversal of TSOACs.

  9. Anticoagulation in chronic kidney disease patients—the practical aspects

    PubMed Central

    Hughes, Stephen; Szeki, Iren; Nash, Michael J.; Thachil, Jecko

    2014-01-01

    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 a high-risk group for thrombosis both in the cardiovascular territory and also in the venous circulation. At the same time, abnormalities in the platelet membranes put them at risk of bleeding which is significantly more than other patients with chronic diseases. Anticoagulation may be ideal to prevent the former, but the co-existing bleeding risk and also that the commonly used drugs for inhibiting coagulation are eliminated by renal pathways pose additional problems. In this review, we try to explain the complex thrombotic-haemorrhagic state of chronic kidney disease patients, and practical considerations for the management of anticoagulation in them with a focus on heparins. PMID:25878775

  10. Endovascular Embolization of Spontaneous Retroperitoneal Hemorrhage Secondary to Anticoagulant Treatment

    SciTech Connect

    Isokangas, Juha-Matti Peraelae, Jukka M.

    2004-11-15

    The purpose of this study was to report a single hospital's experience of endovascular treatment of patients with retroperitoneal hemorrhage (RPH) secondary to anticoagulant treatment. Ten consecutive patients treated in an intensive care unit and needing blood transfusions due to RPH secondary to anticoagulation were referred for digital subtraction angiography (DSA) to detect the bleeding site(s) and to evaluate the possibilities of treating them by transcatheter embolization. DSA revealed bleeding site(s) in all 10 patients: 1 lumbar artery in 4 patients, 1 branch of internal iliac artery in 3 patients and multiple bleeding sites in 3 patients. Embolization could be performed in 9 of them. Coils, gelatin and/or polyvinyl alcohol were used as embolic agents. Bleeding stopped or markedly decreased after embolization in 8 of the 9 (89%) patients. Four patients were operated on prior to embolization, but surgery failed to control the bleeding in any of these cases. Abdominal compartment syndrome requiring surgical or radiological intervention after embolization developed in 5 patients. One patient died, and 2 had sequelae due to RPH. All 7 patients whose bleeding stopped after embolization had a good clinical outcome. Embolization seems to be an effective and safe method to control the bleeding in patients with RPH secondary to anticoagulant treatment when conservative treatment is insufficient.

  11. Popular naturally occurring antioxidants as potential anticoagulant drugs.

    PubMed

    Bijak, Michal; Saluk, Joanna; Szelenberger, Rafal; Nowak, Pawel

    2016-09-25

    Blood coagulation is a physiological process whose main task is prevention of blood loss from injured vessels. This process consists of a series of zymogens proteolytic activation leading to the generation of the main coagulation enzyme - thrombin. Besides its important role in blood coagulation process, thrombin is involved in many cardiovascular diseases, which are responsible for almost half of fatalities in economically developed countries. The evidence for the increased generation and in vivo activity of thrombin was observed in the plasma of individuals at high risk for clinically significant venous and arterial thromboembolic complications. Antioxidants activity of plants extracts has been well known for many years and was confirmed by many publications. However, during the last decade many research centers presented results suggesting anticoagulant potential of various plant extracts. Many researchers have also provided evidence that polyphenol compounds are able to inhibit the activity of many enzymes, including serine proteases. All research described in this review clearly indicate that polyphenols and polyphenol-rich extracts possess not only antioxidative but also anticoagulant properties and may be useful in creation of new therapeutic agents or dietary supplements. Based on described properties polyphenols would be very helpful with both prevention and treatment of thromboembolic complications associated with multiple failures of haemostasis, because the available therapeutic agents do not offer such double-effects (antioxidant and anticoagulant). PMID:27475864

  12. Anticoagulation in pregnant women with prosthetic heart valves.

    PubMed

    Danik, Stephan; Fuster, Valentin

    2004-10-01

    The combination of heart disease and pregnancy can present a formidable challenge to the clinician entrusted to care for both the mother and fetus. Since most data is retrospective, a definitive prognosis for such a patient may be difficult to obtain. Nevertheless, certain cardiac conditions carry greater risks of maternal mortality than do others. However, even for certain preexisting conditions, a tremendous amount of debate persists with respect to risks during pregnancy and optimal peripartum management. One such area of controversy concerns anticoagulation in pregnant women with prosthetic heart valves. For patients who require anticoagulation for mechanical valves, the choice of some combination of warfarin, unfractionated heparin, and low-molecular-weight heparin (LMWH) has resulted in many small-scale trials, which have not yet provided definite guidance as to the best course of action. Even more controversial has been the recent labeling change that advises against the use of LMWH in all patients with prosthetic heart valves, as a result of two cases of prosthetic valve thrombosis in women using LMWH while pregnant. Although the latest product labeling, in the summer of 2003, was changed to a less restrictive recommendation, debate persists. A discussion of the available data on anticoagulation in pregnant women with prosthetic heart valves is presented here, to inform the clinician and the patient of the risks and benefits of the options presently available. PMID:15543433

  13. [The role of new oral anticoagulants in cerebrovascular diseases].

    PubMed

    Orosz, Péter

    2015-12-01

    Cardioembolisation is responsible for 20 percent of ischaemic stroke cases, which most commonly derives from non-valvular atrial fibrillation. Although warfarin is highly effective in primary and secondary stroke prevention, its use is limited by the high risk of haemorrhagic complications and a narrow therapeutic range that needs regular monitoring of INR. These limitations explained the strong need for developing new oral anticoagulants. The so-called 'new oral anticoagulants' are trying to find new targets for modifying the coagulation cascade. Apixaban, edoxaban and rivaroxaban are direct factor Xa inhibitors, while dabigatran works as a direct thrombin inhibitor. Recent phase-III clinical trials proved their effectiveness in stroke prevention and risk reducing of haemorrhagic events as well, so they can already be found as recommended drugs in new guidelines of European and American societies of cardiology and stroke. The use of new oral anticoagulants instead of warfarin in patients with atrial fibrillation or as a secondary prevention after cardioembolic stroke has to be considered. PMID:26727722

  14. Anticoagulation in chronic kidney disease patients-the practical aspects.

    PubMed

    Hughes, Stephen; Szeki, Iren; Nash, Michael J; Thachil, Jecko

    2014-10-01

    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 a high-risk group for thrombosis both in the cardiovascular territory and also in the venous circulation. At the same time, abnormalities in the platelet membranes put them at risk of bleeding which is significantly more than other patients with chronic diseases. Anticoagulation may be ideal to prevent the former, but the co-existing bleeding risk and also that the commonly used drugs for inhibiting coagulation are eliminated by renal pathways pose additional problems. In this review, we try to explain the complex thrombotic-haemorrhagic state of chronic kidney disease patients, and practical considerations for the management of anticoagulation in them with a focus on heparins. PMID:25878775

  15. Reversal of dabigatran anticoagulation ex vivo: Porcine study comparing prothrombin complex concentrates and idarucizumab.

    PubMed

    Honickel, Markus; Treutler, Stefanie; van Ryn, Joanne; Tillmann, Sabine; Rossaint, Rolf; Grottke, Oliver

    2015-04-01

    Urgent surgery or life-threatening bleeding requires prompt reversal of the anticoagulant effects of dabigatran. This study assessed the ability of three- and four-factor prothrombin complex concentrate (PCC) and idarucizumab (specific antidote for dabigatran) to reverse the anticoagulant effects of dabigatran in a porcine model of trauma. Twelve animals were given dabigatran etexilate (DE) orally and dabigatran intravenously, before infliction of trauma. Six animals received tranexamic acid plus fibrinogen concentrate 12 minutes post-injury. Six PCCs (each 30 and 60 U/kg) and idarucizumab (30 and 60 mg/kg) were added to blood samples ex vivo. Coagulation was assessed by several coagulation assays. All coagulation parameters were altered after dabigatran infusion (plasma level: 442 ± 138 ng/ml). Both three- and four-factor PCCs mostly or completely reversed the effects of dabigatran on thromboelastometry variables and PT but not on aPTT. Idarucizumab neutralised plasma concentrations of dabigatran, and reversed the effects of the drug on coagulation variables. Thrombin generation showed dose-dependent over-correction following the addition of PCC, implying that elevated levels of thrombin are required to overcome dabigatran-induced coagulopathy. In contrast, treatment with idarucizumab returned thrombin generation to baseline levels. Following trauma, therapy with tranexamic acid plus fibrinogen improved correction of coagulation parameters by PCC, and thromboelastometry parameters by idarucizumab. All investigated PCCs improved dabigatran- and trauma-induced coagulopathy to a similar degree. In conclusion, this study shows that three- and four-factor PCCs are similarly effective for dabigatran reversal. Idarucizumab also reversed the effects of dabigatran and, unlike PCCs, was not associated with over-correction of thrombin generation.

  16. Use of Dabigatran for Peri-Procedural Anticoagulation in Patients Undergoing Catheter Ablation for Atrial Fibrillation

    PubMed Central

    Bassiouny, Mohamed; Saliba, Walid; Rickard, John; Shao, Mingyuan; Sey, Albert; Diab, Mariam; Martin, David O.; Hussein, Ayman; Khoury, Maurice; Abi-Saleh, Bernard; Alam, Samir; Sengupta, Jay; Borek, P. Peter; Baranowski, Bryan; Niebauer, Mark; Callahan, Thomas; Varma, Niraj; Chung, Mina; Tchou, Patrick J.; Kanj, Mohamed; Dresing, Thomas; Lindsay, Bruce D.; Wazni, Oussama

    2013-01-01

    Background Pulmonary vein isolation (PVI) for atrial fibrillation (AF) is associated with a transient increased risk of thromboembolic and hemorrhagic events. We hypothesized that dabigatran can be safely used as an alternative to continuous warfarin for the peri-procedural anticoagulation in PVI. Methods and Results 999 consecutive patients undergoing PVI were included; 376 patients were on dabigatran (150 mg) and 623 were on warfarin with therapeutic INR. Dabigatran was held 1 to 2 doses prior to PVI and restarted at the conclusion of the procedure or as soon as patients were transferred to the nursing floor. Propensity score matching was applied to generate a cohort of 344 patients in each group with balanced baseline data. Total hemorrhagic and thromboembolic complications were similar in both groups, before (3.2% vs 3.9%; p = 0.59), and after (3.2% vs 4.1%; p = 0.53) matching. Major hemorrhage occurred in 1.1% vs 1.6% (p = 0.48) before, and 1.2% vs 1.5% (p = 0.74) after matching in the dabigatran vs warfarin group respectively. A single thromboembolic event occurred in each of the dabigatran and warfarin groups. Despite higher doses of intra-procedural heparin, the mean ACT was significantly lower in patients who held dabigatran for 1 or 2 doses than those on warfarin. Conclusions Our study found no evidence to suggest a higher risk of thromboembolic or hemorrhagic complications with use of dabigatran for peri-procedural anticoagulation in patients undergoing PVI compared to uninterrupted warfarin therapy. PMID:23553523

  17. A systematic review on the use of new anticoagulants in pregnancy

    PubMed Central

    Tang, Ai-Wei; Greer, Ian

    2013-01-01

    New anticoagulants such as direct factor Xa inhibitors and direct thrombin inhibitors have been recently developed, but their experience in pregnancy is limited. This review therefore aims to systematically search for studies on the use of these newer anticoagulants in pregnancy and the puerperal period. Searches were performed on electronic databases MEDLINE (from 1966), EMBASE (from 1974) and the Cochrane Library, until October 2011 using terms of ‘pregnancy’, ‘puerperium’, ‘breastfeeding’ and names of specific anticoagulants. The search yielded 561 citations and 11 studies (10 on fondaparinux, 1 on ximelagatran) were included. Newer anticoagulants (fondaparinux, hirudin and argatroban) on the limited evidence appear not to have adverse pregnancy outcomes, but there is currently no experience of new oral anticoagulants (rivaroxaban, apixaban, betrixaban or dabigatran) use in pregnancy. There is a need for reporting on new oral anticoagulation use in pregnancy to provide more information about the safety and risks to the fetus in utero.

  18. X-ray structures of the anticoagulants coumatetralyl and chlorophacinone. Theoretical calculations and SAR investigations on thirteen anticoagulant rodenticides

    NASA Astrophysics Data System (ADS)

    Dolmella, A.; Gatto, S.; Girardi, E.; Bandoli, G.

    1999-12-01

    Coumatetralyl and chlorophacinone, two substances related to 4-hydroxycoumarin (HC) and to 1,3-indandione (ID), respectively, show activity as anticoagulant rodenticides. In the present study we have investigated the solid-state structures of coumatetralyl and chlorophacinone by means of X-ray single-crystal and powder diffraction, along with thermal analysis. The crystal structures of the two compounds have been used as input geometries for a series of computational chemistry efforts, involving other anticoagulant derivatives as well. Thus, ab initio, semiempirical molecular orbital, molecular mechanics and molecular dynamics/simulated annealing calculations have been performed on thirteen anticoagulant rodenticides. In particular, the annealing calculations have been made to assess the conformational freedom of the compounds under scrutiny. All the generated conformers have been classified into families. The classification has first been made empirically, and then validated by means of a cluster analysis. A number of structural and physico-chemical parameters derived from the calculations has been used in turn for structure-activity relationships (SARs) investigations. In the latter, we have assessed how the selected parameters affect toxicity. The results seem to be consistent with a three-dimensional biophore model, in which higher toxicity is predicted for the more voluminous rodenticides. We suggest that these compounds better fit the active site of the target enzyme vitamin K 2,3-epoxide reductase (KO-reductase).

  19. Treatment of High-risk Venous Thrombosis Patients Using Low-dose Intraclot Injections of Recombinant Tissue Plasminogen Activator and Regional Anticoagulation

    PubMed Central

    Chang, Richard; Butman, John A.; Lonser, Russell R.; Sherry, Richard M.; Pandalai, Prakash K.; Horne, McDonald K.; Lozier, Jay N.

    2013-01-01

    Seven patients with venous thrombosis and contraindications to traditional thrombolytic therapy, consisting of recent intracranial surgery, recent pineal or retroperitoneal hemorrhage, active genitourinary or gastrointestinal bleeding, epidural procedures, and impending surgery, were successfully treated with a modified thrombolytic regimen. To improve safety, prolonged continuous infusions of tissue plasminogen activator (tPA) was eliminated in favor of once-daily low-dose intraclot injections of tPA to minimize the amount and duration of tPA in the systemic circulation, and low-therapeutic or regional anticoagulation was used to reduce anticoagulant risks. These modifications may allow thrombolytic treatment for selected patients with severe venous thrombosis who are deemed to be at high risk. PMID:23273695

  20. Practical and clinical considerations in assessing patients with atrial fibrillation for switching to non-vitamin K antagonist oral anticoagulants in primary care

    PubMed Central

    Guimarães, Patrícia O; Kaatz, Scott; Lopes, Renato D

    2015-01-01

    Atrial fibrillation (AF) is an important risk factor for thromboembolic events, and anticoagulation therapy can reduce this risk. Vitamin K antagonists (VKAs), such as warfarin, have been used for decades in patients with AF for stroke prevention. Currently, non-VKA oral anticoagulants (NOACs) are approved and available for non-valvular AF patients who are at increased risk of stroke. These agents are safe and effective and have important advantages over VKAs, such as significant reduction in intracranial hemorrhage and no need for routine laboratory monitoring. Thus, should all VKA-treated patients be switched to a NOAC? The aims of this article are: 1) to review the advantages of NOACs over VKAs; 2) to identify the group of patients who most benefit from receiving a NOAC and, therefore, are higher priority to be switched from VKAs; and 3) to provide clinical and practical guidance on how to switch patients safely from VKAs to NOACs. PMID:26379443

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

    Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation. PMID:26273933

  3. A new paradigm shift in antithrombotic therapy

    PubMed Central

    Pudusseri, Anita; Shameem, Raji; Spyropoulos, Alex C.

    2013-01-01

    Decades after the introduction of oral anti-coagulants namely the vitamin K antagonist (VKA) Warfarin and antiplatelet agents such as Aspirin and Plavix, new classes of direct, small molecule, novel oral anti-coagulant medications and antiplatelet P2Y12 receptor inhibitors have recently become available. For the novel oral anticoagulants (NOAC), these agents can be separated by direct thrombin inhibitors such as Dabigatran and direct Factor Xa inhibitors such as Rivaroxaban and Apixaban. For next generation antiplatelet agents such as Ticagrelor and Prasugrel, these new P2Y12 receptor inhibitors form the cornerstone of therapy for patients with acute coronary syndrome (ACS) or undergoing percutaneous interventions. These novel oral antithrombotics are revolutionizing the field of stroke prevention, atrial fibrillation (AF), the management of venous thromboembolism (VTE) and treatment of ACS. This article reviews the current research developed in order to identify therapeutic effects and establish net clinical benefits of these new oral antithrombotics. PMID:24155721

  4. [Bleeding, the Achilles' heel in patients treated with anticoagulants. Approach in patients with atrial fibrillation].

    PubMed

    Morais, João

    2012-04-01

    Bleeding is always the Achilles' heel of all antithrombotic therapy, being unthinkable to use this type of therapy ignoring the complications that it may arise. The bleeding risk raises very particular problems, namely how to predict it and how to manage it. The withdrawal of antithrombotic drugs and transfusion are two important practical problems, involving clinical decisions that are generally very difficult. The new oral anticoagulants pose new problems. If on the one hand its bleeding risk appears to be less, specially in what concerns intracranial bleeding and potentially life-threatening bleeding, on the other hand the lack of an antidote or the lack of a quick and effective laboratory test to evaluate its efficacy, are arguments used by the critics. The risk of bleeding is conditioned by several factors, among them old age. The elderly patient is, by definition, the patient that can bleed more but also the one that, due to its ischemic risk, can reap more benefit. In this paper some of the tools used to predict the risk of bleeding and its clinical impact are also presented.

  5. Evaluation of a Heparin-Calibrated Antifactor Xa Assay for Measuring the Anticoagulant Effect of Oral Direct Xa Inhibitors.

    PubMed

    Beyer, Jacob; Trujillo, Toby; Fisher, Sheila; Ko, Ann; Lind, Stuart E; Kiser, Tyree H

    2016-07-01

    The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations.

  6. Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

    PubMed Central

    Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

    2015-01-01

    Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12

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

    PubMed Central

    da Costa, Mário Augusto Cray; Krum, Lucas Kraeski; Geraldino, Juliana da Silva; Schafranski, Marcelo Derbli; Gomes, Ricardo Zanetti; Reis, Elise Souza dos Santos

    2016-01-01

    INTRODUCTION: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. OBJECTIVE: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. METHODS: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding) and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. RESULTS: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli); 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001). Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04). Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03), less annual consultations (P=0.02) and less dose adjustments (P=0.003). Patients with longer duration of anticoagulation have more complications (P=0.001). CONCLUSION: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of anticoagulation. PMID:27737407

  8. Evaluating the Initiation of Novel Oral Anticoagulants in Medicare Beneficiaries

    PubMed Central

    Baik, Seo Hyon; Hernandez, Inmaculada; Zhang, Yuting

    2016-01-01

    BACKGROUND As alternatives to warfarin, 2 novel oral anticoagulants (NOACs), dabigatran and rivaroxaban, were approved in 2010 and 2011 to prevent stroke and other thromboembolic events in patients with atrial fibrillation. It is unclear how patient characteristics are associated with the initiation of anticoagulants. OBJECTIVE To evaluate how patient demographics, clinical characteristics, types of insurance, and patient out-of-pocket spending affect the initiation of warfarin and 2 NOACs—dabigatran and rivaroxaban. METHODS We used pharmacy claims data from a 5% random sample of Medicare beneficiaries to identify patients who were newly diagnosed with atrial fibrillation between October 1, 2010, and October 31, 2012, and who were prescribed an oral anticoagulant within 60 days of diagnosis. We identified key predictors of initiation of NOACs using a multinomial logistic regression model with generalized logit link. RESULTS Patients who were black and who had a history of acute myocardial infarction, stroke or transient ischemic attack, chronic kidney disease, or congestive heart failure were significantly associated with lower odds of receiving NOACs compared with warfarin. Age greater than 65 years, a history of hypertension, and use of nonsteroidal anti-inflammatory drugs were positively associated with the initiation of NOACs. Rivaroxaban was most likely to be initiated among women, followed by warfarin and dabigatran. Individuals receiving a low-income subsidy were more likely to initiate warfarin than NOACs, even though they paid little copayment. Individuals with supplemental Part D drug coverage, such as national Programs for All-Inclusive Care for the Elderly or employer-sponsored plans, were more likely to initiate NOACs compared with warfarin. CONCLUSIONS We found that race, sex, type of Part D plans, and some clinical conditions were associated with the initiation of NOACs relative to warfarin. But patient demographic and clinical characteristics did

  9. Challenges encountered with argatroban anticoagulation during cardiopulmonary bypass

    PubMed Central

    Agarwal, Shvetank; Ullom, Beth; Al-Baghdadi, Yasser; Okumura, Michael

    2012-01-01

    Use of argatroban as an alternative to heparin during cardiopulmonary bypass (CPB) in patients with heparin-induced thrombocytopenia has gained some attention in the past two decades. Dosing of argatroban during CPB is complex due to lack of complete understanding of its pharmacokinetic profile and the various elements during CPB that may alter its plasma levels. We report a case where the challenges in dosing argatroban led to failure to provide adequate anticoagulation during CPB, as evidenced by clot formation in the oxygenator, and extensive bleeding in the postoperative period. PMID:22345956

  10. [More with atrial fibrillation, anticoagulants since the coming of NOAK ].

    PubMed

    Forslund, Tomas; von Euler, Mia; Johnsson, Hans; Holmström, Margareta; Wettermark, Björn; Hjemdahl, Paul

    2015-01-01

    Since the introduction of NOAC (non-vitamin K antagonist oral anticoagulants) in 2011 as thromboprophylactic treatment for patients with atrial fibrillation, AF, the number of patients with a diagnosis of atrial fibrillation has increased markedly in our health care registers. The proportion of patients treated with warfarin or NOAC has increased from 47 % to 58 % in 2013. The use of acetylsalicylic acid in patients is decreasing rapidly in patients with AF. NOAC are mostly prescribed by specialists and are mainly used in younger patients with lower CHA2DS2-VASc scores and lower risk for renal insufficiency and bleeding. PMID:25584610

  11. [Oral anticoagulation in chronic kidney disease with atrial fibrillation].

    PubMed

    Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema

    2015-05-21

    Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain.

  12. A new dicoumarin and anticoagulant activity from Viola yedoensis Makino.

    PubMed

    Zhou, Hai Yan; Hong, Jun Li; Shu, Pan; Ni, Yue Juan; Qin, Min Jian

    2009-07-01

    A new dicoumarin, named as dimeresculetin (1), together with another dicoumarin, euphorbetin (2) and esculetin (3) were isolated from the ethyl acetate extract of the dried whole plants of Viola yedoensis Makino. The structure of 1 was elucidated as 7-hydroxy-6-[(6,7-dihydroxy-2-oxo-2H-1-benzopyran-5-yl)oxy]-2H-1-benzopyran-2-one on the basis of extensive NMR, as well as the other spectral analysis. Compounds 1-3 exhibited anticoagulant activities with respect to activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT).

  13. A rare cause of recurrent cerebral emboli despite oral anticoagulation

    PubMed Central

    Dzialowski, Imanuel; Wolz, Martin; Meinhardt, Matthias; Waldow, Thomas

    2014-01-01

    We report on a patient with a history of colon carcinoma and clinical presentation of recurrent cardiac emboli despite oral anticoagulation for atrial fibrillation. On delayed transoesophageal echocardiography, finally a left atrial myxoma was suspected. Surgery, however, revealed a left atrial metastatic tumour with histopathological features of a colon adenocarcinoma. Metastases of colorectal adenocarcinoma invading cardiac structures are rare. Isolated literature reports describe metastatic masses detected in the right atrium reflecting natural haematogenous spreading of cancer, but none in the left heart. PMID:25246459

  14. Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation.

    PubMed

    Plitt, Anna; Ruff, Christian T; Giugliano, Robert P

    2016-10-01

    For more than 50 years, vitamin K antagonists (VKAs) have been the standard of care for treatment of atrial fibrillation (AF). However, the numerous limitations of VKAs have led to the development of non-VKA oral anticoagulants (NOACs). There are 4 NOACs currently approved for prevention of thromboembolism in patients with nonvalvular AF. This article provides an overview of AF, summarizes basic properties of NOACs, and reviews the landmark trials. Current data on use of NOACs in special populations and specific clinical scenarios are also presented. Lastly, recommendations from experts on controversial topics of bleeding management and reversal are described. PMID:27637305

  15. [Oral anticoagulation in chronic kidney disease with atrial fibrillation].

    PubMed

    Expósito, Víctor; Seras, Miguel; Fernández-Fresnedo, Gema

    2015-05-21

    Atrial fibrillation is a common finding in patients with chronic kidney disease (CKD), which increases markedly the embolism risk. The CHADS2 and HAS-BLED scales, used in the general population to assess the risk/benefit of oral anticoagulation (OAC), underestimate respectively the risk of embolism and haemorrhage in CKD, making it difficult to decide whether to use OAC or not. Based on the available evidence, it seems indicated to use OAC in stage 3 CKD, while it is controversial in advanced stages. New OAC such as dabigatran and rivaroxaban have been approved in stage 3 CKD but their role is still somewhat uncertain. PMID:24889748

  16. Should we revisit anticoagulation guidelines during thyroid storm?

    PubMed

    Petersen, Andrew W; Puig-Carrión, Gisela D; López-Candales, Angel

    2015-01-01

    Thyroid storm is a rare but potentially catastrophic disease expression of thyrotoxicosis with well-recognized cardiovascular manifestations such as heart failure and atrial fibrillation. Even through some studies have found an increased risk of cardiac thrombus formation and subsequent thromboembolism in these patients, the use of anticoagulation to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation remains unclear. We present a patient presenting with new onset dilated cardiomyopathy and resistant atrial fibrillation with thyroid storm that had a large left atrial appendage clot. Case particulars are discussed and the literature reviewed. PMID:26035989

  17. Antithrombotic Therapy for VTE Disease

    PubMed Central

    Kearon, Clive; Comerota, Anthony J.; Prandoni, Paolo; Bounameaux, Henri; Goldhaber, Samuel Z.; Nelson, Michael E.; Wells, Philip S.; Gould, Michael K.; Dentali, Francesco; Crowther, Mark; Kahn, Susan R.

    2012-01-01

    Background: This article addresses the treatment of VTE disease. Methods: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence. Results: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C). Conclusion: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. PMID:22315268

  18. Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...

  19. Non-vitamin K antagonist oral anticoagulants and atrial fibrillation guidelines in practice: barriers to and strategies for optimal implementation

    PubMed Central

    Camm, A. John; Pinto, Fausto J.; Hankey, Graeme J.; Andreotti, Felicita; Hobbs, F.D. Richard

    2015-01-01

    Stroke is a leading cause of morbidity and mortality worldwide. Atrial fibrillation (AF) is an independent risk factor for stroke, increasing the risk five-fold. Strokes in patients with AF are more likely than other embolic strokes to be fatal or cause severe disability and are associated with higher healthcare costs, but they are also preventable. Current guidelines recommend that all patients with AF who are at risk of stroke should receive anticoagulation. However, despite this guidance, registry data indicate that anticoagulation is still widely underused. With a focus on the 2012 update of the European Society of Cardiology (ESC) guidelines for the management of AF, the Action for Stroke Prevention alliance writing group have identified key reasons for the suboptimal implementation of the guidelines at a global, regional, and local level, with an emphasis on access restrictions to guideline-recommended therapies. Following identification of these barriers, the group has developed an expert consensus on strategies to augment the implementation of current guidelines, including practical, educational, and access-related measures. The potential impact of healthcare quality measures for stroke prevention on guideline implementation is also explored. By providing practical guidance on how to improve implementation of the ESC guidelines, or region-specific modifications of these guidelines, the aim is to reduce the potentially devastating impact that stroke can have on patients, their families and their carers. PMID:26116685

  20. Clinical strategies for selecting oral anticoagulants in patients with atrial fibrillation

    PubMed Central

    Sherwood, Matthew W.; Becker, Richard C.

    2014-01-01

    Atrial fibrillation is a common arrhythmia. One of the important aspects of the management of atrial fibrillation is stroke prevention. Warfarin has been the longstanding anticoagulant used for stroke prevention in patients with atrial fibrillation. There are now three novel oral anticoagulants, which have been studied in randomized controlled trials and subsequently approved by the Federal Drug Administration for stroke prevention in patients with atrial fibrillation. Special patient populations, including renal insufficiency, elderly, prior stroke, and extreme body weights, were represented to varying degrees in the clinical trials of the novel oral anticoagulants. Furthermore, there is variation in the pharmacokinetics and pharmacodynamics of each anticoagulant, which affect the patient populations differently. Patients and clinicians are faced with the task of selecting among the available anticoagulants, and this review is designed to be a tool for clinical decision-making. PMID:23846737

  1. Neonatal renal vein thrombosis: role of anticoagulation and thrombolysis--an institutional review.

    PubMed

    Bidadi, Behzad; Nageswara Rao, Amulya A; Kaur, Dominder; Khan, Shakila P; Rodriguez, Vilmarie

    2016-02-01

    Neonatal renal vein thrombosis (NRVT) is a rare thromboembolic complication in the neonatal period, and sequelae from renal dysfunction can cause significant morbidity. The authors retrospectively reviewed 10 patients with NRVT treated at their institution. The majority of the cohort were male (n = 9), preterm (n = 6), and had unilateral NRVT (n = 6). Six patients received thrombolysis and/or anticoagulation, and 4 patients received supportive care only. Two of the 6 patients treated with anticoagulation who had bilateral NRVT and anuria received thrombolysis with low-dose tissue plasminogen activator. Thrombolysis was not associated with any major adverse events, and both patients had marked improvement of renal function. Eight patients subsequently developed renal atrophy (3 received anticoagulation, 2 received thrombolysis with anticoagulation, and 3 received supportive care). Anticoagulation/thrombolysis did not appear to prevent renal atrophy. The role of thrombolysis needs to be further studied and considered in the setting of bilateral NRVT and acute renal failure.

  2. Comparative study of two portable systems for oral anticoagulant monitoring.

    PubMed

    Vacas, Marta; Lafuente, Pedro José; Unanue, Iciar; Iriarte, José Antonio

    2004-01-01

    Portable prothrombin time (PT) monitors offer the potential for both simplifying and improving oral anticoagulation management. It is necessary to evaluate their concordance and correlation with other PT systems. Our objective was to evaluate the concordance and clinical correlation of two portable PT determination systems, ProTime (ITC) and CoaguChek S (Roche Diagnostics). In all, 20 healthy individuals and 60 anticoagulated patients stabilized over 3 months in a therapeutic International Normalized Ratio (INR) range between 2-3.5 were studied. A drop of capillary blood was obtained simultaneously from two different fingers of each patient and applied to the monitor's application zone. The mean INR of the patients' blood samples of the two monitors differed by 0.01 units (2.32+/-0.63 for Pro Time and 2.33+/-0.68 for CoaguChek). The percentage of simple concordance and the kappa index were 88.3 and 75.9%, respectively. The coefficient of correlation was 0.922. The mean difference (bias) between the monitors was 0.01. The portable PT monitors evaluated presented a high percentage of concordance in INR results.

  3. The factor XIIa blocking antibody 3F7: a safe anticoagulant with anti-inflammatory activities

    PubMed Central

    Worm, Marie; Köhler, Elodie C.; Panda, Rachita; Long, Andy; Butler, Lynn M.; Stavrou, Evi X.; Nickel, Katrin F.; Fuchs, Tobias A.

    2015-01-01

    The plasma protein factor XII (FXII) is the initiating protease of the procoagulant and proinflammatory contact system. FXII activates both the bradykinin (BK) producing kallikrein-kinin system and the intrinsic pathway of coagulation. Contact with negatively charged surfaces induces auto-activation of zymogen FXII that results in activated FXII (FXIIa). Various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, nucleic acids and polyphosphate. Murine models have established a central role of FXII in arterial and venous thromboembolic diseases. Despite the central function of FXII in pathologic thrombosis, its deficiency does not impair hemostasis in animals or humans. The selective role of FXIIa in thrombosis, but not hemostasis, offers an exciting novel strategy for safe anticoagulation based on interference with FXIIa. We have generated the recombinant fully human FXIIa-blocking antibody 3F7, which abolished FXIIa enzymatic activity and prevented thrombosis in a cardiopulmonary bypass system in large animals, in the absence of increased therapy-associated bleeding. Furthermore, 3F7 also interfered with BK-driven edema in the severe swelling disorder hereditary angioedema (HAE) type III. Taken together, targeting FXIIa with 3F7 appears to be a promising approach to treat edema disorders and thrombosis. PMID:26605293

  4. Spontaneous Subcapsular Renal Hematoma: Strange Case in an Anticoagulated Patient with HWMH after Aortic and Iliac Endovascular Stenting Procedure.

    PubMed

    Greco, Michele; Butticè, Salvatore; Benedetto, Filippo; Spinelli, Francesco; Traxer, Olivier; Tefik, Tzevat; Pappalardo, Rosa; Magno, Carlo

    2016-01-01

    Spontaneous subcapsular renal hematoma is a rare condition in clinical practice. It is caused by renal cysts, benign and malignant renal tumors, vascular lesions, and antiplatelet or anticoagulant therapy. In this paper we report an unusual case of rupture of a renal cyst of a 66-year-old male patient during an aortic and iliac endovascular procedure for a massive calcified atheroma above the iliac bifurcation. We suspected that the bolus of high weight molecular heparin given during the procedure caused the rupture of the cyst. According to the literature, this is the first case of renal cyst rupture during an endovascular aortic procedure after administering a high weight molecular heparin bolus. PMID:27579210

  5. Spontaneous Subcapsular Renal Hematoma: Strange Case in an Anticoagulated Patient with HWMH after Aortic and Iliac Endovascular Stenting Procedure

    PubMed Central

    Greco, Michele; Benedetto, Filippo; Spinelli, Francesco; Traxer, Olivier; Tefik, Tzevat; Pappalardo, Rosa

    2016-01-01

    Spontaneous subcapsular renal hematoma is a rare condition in clinical practice. It is caused by renal cysts, benign and malignant renal tumors, vascular lesions, and antiplatelet or anticoagulant therapy. In this paper we report an unusual case of rupture of a renal cyst of a 66-year-old male patient during an aortic and iliac endovascular procedure for a massive calcified atheroma above the iliac bifurcation. We suspected that the bolus of high weight molecular heparin given during the procedure caused the rupture of the cyst. According to the literature, this is the first case of renal cyst rupture during an endovascular aortic procedure after administering a high weight molecular heparin bolus. PMID:27579210

  6. Longest Event-Free Survival without Anticoagulation in a Mechanical Aortic Valve Replacement

    PubMed Central

    Salmane, Chadi; Pandya, Bhavi; Lafferty, Kristen; Patel, Nileshkumar J; McCord, Donald

    2016-01-01

    Sixty percent of the patients going for valve replacement opt for mechanical valves and the remaining 40% choose bioprosthetics. Mechanical valves are known to have a higher risk of thrombosis; this risk further varies depending on the type of valve, its position, and certain individual factors. According to current guidelines, long-term anticoagulation is indicated in patients with metallic prosthetic valve disease. We report two unique cases of patients who survived 27 and 37 years event free, respectively, after mechanical aortic valve replacement (AVR) without being on any form of anticoagulation. The latter case described the longest survival in a human with a prosthetic aortic valve without anticoagulation. A review of literature demonstrated few cases of prosthetic valves with no anticoagulation in the long term without significant embolic events reported as case reports. These cases have been summarized in this article. Some cases of long-term survival (in the absence of anticoagulation) were attributed to good luck, and others as the result of genetic variations. New mechanical prosthetic valves can be promising, such as microporus-surfaced valves that may be used without full anticoagulation. The use of dual antiplatelet agents alone can be currently recommended only when a patient cannot take oral anticoagulation after AVR, and it should be followed with measuring and monitoring of platelet reactivity. PMID:27053922

  7. Usefulness of transoesophageal echocardiography before cardioversion in patients with atrial fibrillation and different anticoagulant regimens

    PubMed Central

    Maltagliati, A; Galli, C A; Tamborini, G; Calligaris, A; Doria, E; Salehi, R; Pepi, M

    2006-01-01

    Objectives To evaluate the prevalence of atrial thrombi in patients with atrial fibrillation undergoing different anticoagulation regimens before cardioversion; to evaluate the usefulness of transoesophageal echocardiography (TOE) guided cardioversion to prevent thromboembolic complications; and to correlate the presence of atrial thrombi with clinical and echocardiographic data. Methods 757 consecutive patients admitted as candidates for cardioversion of atrial fibrillation were enrolled in the study. They were divided into four groups: effective conventional oral anticoagulation, short term anticoagulation, ineffective oral anticoagulation or subtherapeutic anticoagulation, and effective oral anticoagulation with a duration of < 3 weeks for various clinical reasons. All patients underwent TOE before cardioversion; in the presence of atrial thrombi or extreme left atrial echo contrast, cardioversion was postponed. The incidence of thromboembolic events was evaluated after cardioversion. Results Atrial thrombi were detected in 48 of the 757 (6.3%) patients. No significant differences in the percentage of atrial thrombosis were found in the four study groups. Patients with atrial thrombosis were older and had a higher percentage of mitral prosthetic valves, lower left ventricular ejection fraction, more severe atrial spontaneous echo contrast, and lower Doppler left atrial appendage velocities. 648 patients were scheduled for cardioversion. Cardioversion was successful in 89% of patients without any major thromboembolic event. Conclusions The prevalence of atrial thrombosis before cardioversion despite different treatments with anticoagulants is about 7% and a TOE guided approach may prevent the risk of embolic events. PMID:16284221

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

    PubMed

    LaBonte, Michelle L

    2014-09-01

    Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. PMID:24853975

  9. Concentrations of anticoagulant rodenticides in stoats Mustela erminea and weasels Mustela nivalis from Denmark.

    PubMed

    Elmeros, Morten; Christensen, Thomas Kjær; Lassen, Pia

    2011-05-15

    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

  10. Thrombectomy and Catheter-Directed Thrombolysis Combined With Antithrombin Concentrate for Treatment of Antithrombin Deficiency Complicated by Acute Deep Vein Thrombosis That Is Refractory to Anticoagulation.

    PubMed

    Maeba, Hirofumi; Seno, Takeshi; Shiojima, Ichiro

    2016-09-28

    A 22-year-old male was admitted to our hospital with deep vein thrombosis that was complicated by antithrombin deficiency. This deficiency was refractory to anticoagulation therapy. Although catheter-directed thrombolysis could not reperfuse the total occlusion in the left deep vein, a combination of thrombectomy, catheter-directed thrombolysis, and antithrombin concentrate treatment was able to dissolve the clots and ameliorate the blood flow into the left deep vein. Antithrombin concentrate administration would be effective in the treatment of antithrombin deficiency with medical refractory deep vein thrombosis.

  11. Nature's "silver bullet" for anticoagulation: mechanism of Zymogen Protein C to Activated Protein C.

    PubMed

    Bruley, Duane F; Streiff, Michael B

    2013-01-01

    We have defined the Zymogen Protein C (ZPC) to Activated Protein C (APC) process as the "silver bullet" of blood anticoagulation. This definition suggests that the anticoagulation activity occurs when and where it is needed, resulting in local anticoagulation without enhanced bleeding. It is important for man to be able to manufacture an inexpensive ZPC product or to find a substitute drug to duplicate one of God's natural anticoagulant/antithrombotic processes, in vivo, in human blood. After intense research and at great expense scientists have not been able to produce a safe anticoagulant. All products that are now being used can cause bleeding even if dosing is carefully monitored. In fact many professionals in the health care and the pharmaceutical industries define an anticoagulant as a drug that "does" cause bleeding. This results in a large financial burden that has been placed on the health care industry because of necessary emergency treatments for dangerous occurrences. In addition, many patients are dying annually due to internal and external bleeds created or enhanced by presently administered anticoagulants. Since there are no safe drugs available it is necessary to use the existing products when a medical condition calls for an anticoagulant. This paper will discuss the ZPC process and why its mechanistic design is one of nature's unique defenses against unwanted blood clotting. The prevention and lysis of clots allows normal blood flow and therefore results in the required tissue oxygenation for cell function and survival. If clinical research is carried out with great care it could uncover other uses of ZPC that will allow safer medical procedures, in addition to its use with standard PC deficiency cases. An important example might be for some brain surgeries where the use of existing anticoagulants is unsafe because of potential bleeds. Clinical research could reveal an efficacious ZPC level (for instance, 125, 150, or 200% of normal) that would

  12. Lumbar puncture in patients using anticoagulants and antiplatelet agents.

    PubMed

    Domingues, Renan; Bruniera, Gustavo; Brunale, Fernando; Mangueira, Cristóvão; Senne, Carlos

    2016-08-01

    The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks. PMID:27556380

  13. Effects of pelletized anticoagulant rodenticides on California quail

    USGS Publications Warehouse

    Blus, L.J.; Henny, C.J.; Grove, R.A.

    1985-01-01

    A moribund, emaciated California quail (Callipepla californica) that was found in an orchard in the state of Washington had an impacted crop and gizzard. Pellets containing the anticoagulant chlorophacinone (Rozol, RO) were in the crop; the gizzard contents consisted of a pink mass of paraffin that was selectively accumulated from the paraffinized pellets. The plasma prothrombin time of 28 sec was near that determined for control quail. The signs of RO intoxication seen in the moribund wild quail were duplicated in captive quail given ad libitum diets of either RO or another paraffinized chlorophacinone pellet (Mr. Rat Guard II, MRG). This left little doubt that paraffin impaction of the gizzard was the primary problem. All captive quail fed RO or MRG pellets showed no increases in prothrombin times compared to control values, died in an emaciated condition, and had gizzards impacted with paraffin.

  14. Thrombin-Inhibiting Anticoagulant Liposomes: Development and Characterization.

    PubMed

    Endreas, Wegderes; Brüßler, Jana; Vornicescu, Doru; Keusgen, Michael; Bakowsky, Udo; Steinmetzer, Torsten

    2016-02-01

    Many peptides and peptidomimetic drugs suffer from rapid clearance in vivo; this can be reduced by increasing their size through oligomerization or covalent conjugation with polymers. As proof of principle, an alternative strategy for drug oligomerization is described, in which peptidomimetic thrombin inhibitors are incorporated into the liposome surface. For this purpose, the inhibitor moieties were covalently coupled to a palmitic acid residue through a short bifunctionalized ethylene glycol spacer. These molecules were directly added to the lipid mixture used for liposome preparation. The obtained liposomes possess strong thrombin inhibitory potency in enzyme kinetic measurements and anticoagulant activity in plasma. Their strong potency and positive ζ potential indicate that large amounts of the benzamidine-derived inhibitors are located on the surface of the liposomes. This concept should be applicable to other drug molecules that suffer from rapid elimination and allow covalent modification with a suitable fatty acid residue. PMID:26662675

  15. Activated protein C anticoagulant system dysfunction and thrombophilia in Asia.

    PubMed

    Hamasaki, Naotaka; Kuma, Hiroyuki; Tsuda, Hiroko

    2013-01-01

    Thrombophilia that is common among Caucasians is caused by genetic polymorphisms of coagulation factor V Leiden (R506Q) and prothrombin G20210A. Unlike that in Caucasians, thrombophilia that is common in the Japanese and Chinese involve dysfunction of the activated protein C (APC) anticoagulant system caused by abnormal protein S and protein C molecules. Approximately 50% of Japanese and Chinese individuals who develop venous thrombosis have reduced activities of protein S. The abnormal sites causing the protein S molecule abnormalities are distributed throughout the protein S gene, PROS1. One of the most common abnormalities is protein S Tokushima (K155E), which accounts for about 30% of the protein S molecule abnormalities in the Japanese. Whether APC dysfunction occurs in other Asian countries is an important aspect of mapping thrombophilia among Asians. International surveys using an accurate assay system are needed to determine this.

  16. Anticoagulant flavonoid oligomers from the rhizomes of Alpinia platychilus.

    PubMed

    Shen, Chuan-Pu; Luo, Jian-Guang; Yang, Ming-Hua; Kong, Ling-Yi

    2015-10-01

    Two pairs of enantiomers of flavonoid oligomers (1a and 1b, 2a and 2b) along with one known chalcone (3) were isolated from the rhizomes of Alpinia platychilus. Their structures were elucidated on the basis of spectroscopic data (MS and 1D/2D NMR). The absolute configurations of the flavonoid oligomers were established by their ECD spectra. Separation of the enantiomeric mixtures (1a and 1b, 2a and 2b) was achieved on a chiral column using hexane:isopropyl alcohol:ethanol (7:2:1) as eluents. The anticoagulant assay showed that 2a, 2b and 3 exhibited potent activities to prolong the prothrombin times (PT) and the thrombin times (TT).

  17. Effects of pelletized anticoagulant rodenticides on California quail.

    PubMed

    Blus, L J; Henny, C J; Grove, R A

    1985-10-01

    A moribund, emaciated California quail (Callipepla californica) that was found in an orchard in the state of Washington had an impacted crop and gizzard. Pellets containing the anticoagulant chlorophacinone (Rozol, RO) were in the crop; the gizzard contents consisted of a pink mass of paraffin that was selectively accumulated from the paraffinized pellets. The plasma prothrombin time of 28 sec was near that determined for control quail. The signs of RO intoxication seen in the moribund wild quail were duplicated in captive quail given ad libitum diets of either RO or another paraffinized chlorophacinone pellet (Mr. Rat Guard II, MRG). This left little doubt that paraffin impaction of the gizzard was the primary problem. All captive quail fed RO or MRG pellets showed no increases in prothrombin times compared to control values, died in an emaciated condition, and had gizzards impacted with paraffin. PMID:4078974

  18. Exposure pathways of anticoagulant rodenticides to nontarget wildlife.

    PubMed

    Elliott, John E; Hindmarch, Sofi; Albert, Courtney A; Emery, Jason; Mineau, Pierre; Maisonneuve, France

    2014-02-01

    Second-generation anticoagulant rodenticides are widely reported to contaminate and poison nontarget wildlife, primarily predatory birds and mammals. Exposure pathways, however, have not been well defined. Here, we examined potential movement of rodenticides from deployment of bait to exposure of small mammals and other biota. At two adjacent working farms, we placed baits containing either brodifacoum or bromadiolone. We monitored movement of those compounds to the surrounding environment by collecting small mammals, birds, and invertebrates. Similar collections were made at a third agricultural setting without active bait deployment, but located among intensive livestock production and regular rodenticide use by farmers. Livers and whole invertebrate samples were analyzed for rodenticides using a sensitive LC-MSMS method. Norway rats (Rattus norvegicus) from both baited and non-baited farms had residues of brodifacoum or bromadiolone, implicating rats as an important exposure pathway to wildlife. Among 35 analyzed nontarget small mammals, a single vole had high hepatic residues (18.6 μ/g), providing some indication of a small mammal pathway. One song sparrow (Melospiza melodia) sample from a baited farm contained 0.073 μg/g of brodifacoum in liver, while 0.39 μg/g of diphacinone was measured in a pool of carrion beetles (Dermestes spp.) from the non-baited farm area, implicating avian and invertebrate components in exposure pathways. Regurgitated pellets of barn owl (Tyto alba) selected randomly from baited farms contained no detectable rodenticide residues, while 90% of owl pellets collected from a variety of farms, and selected for the presence of rat fur, contained detectable anticoagulant residues. We recorded behavior of a captive sample of a representative songbird, the house sparrow (Passer domesticus); they readily entered bait stations and fed on (unloaded) bait. PMID:24048882

  19. New anticoagulants for the prevention of stroke in atrial fibrillation.

    PubMed

    Höchtl, Thomas; Huber, Kurt

    2012-02-01

    Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of spontaneous cerebrovascular and systemic thromboembolism. For this purpose, vitamin K antagonists (coumarins) have been recommended as the most effective drugs for a long time. However, problems with the practical use of these agents, e.g. the need for frequent and regular coagulation controls, the inter-individual differences in maintaining a stable therapeutic range, as well as drug or food interactions, have led to the search and investigation of alternative compounds characterized by a more simple use (e.g. without regular controls of therapeutic levels), high efficacy, as well as low risk of bleeding. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban have recently been investigated to prove whether they fulfill the high expectancy of an ideal anticoagulant with respect to a more favorable efficacy/safety profile and without the need for coagulation controls, thereby improving quality of life. Dabigatran (RE-LY) achieved an impressive reduction in stroke and non-central nervous system (non-CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year) in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable action on bleeding hazards. The results of rivaroxaban which were obtained in the ROCKET AF study (on treatment analysis: stroke and non-CNS embolism: 1.7%/year vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally, compared to aspirin, apixaban reduced the combined primary efficacy endpoint by 52% with comparable rates of bleeding (AVERROES). This review gives a summary of the current knowledge about these agents and their potential future importance. PMID:21883447

  20. Non-vitamin K antagonist oral anticoagulants (NOACs): a view from the laboratory.

    PubMed

    Blann, A D

    2014-01-01

    Disadvantages with traditional anticoagulants (vitamin K antagonists and heparinoids) have led to the development on non-vitamin K antagonist oral anticoagulants (NOACs). These agents are set to replace the traditional anticoagulants in situations such as following orthopaedic surgery, in atrial fibrillation, and in the prevention and treatment of venous thromboembolism. Although superior to vitamin K antagonists and heparinoids in several aspects, NOACs retain the ability to cause haemorrhage and, despite claims to the contrary, may need monitoring. This review aims to summarise key aspects of the NOACs of relevance to the laboratory. PMID:25562993

  1. Bivalirudin anticoagulation for minimal invasive transapical transcatheter aortic valve replacement in a patient with antiphospholipid antibodies.

    PubMed

    Koster, Andreas; Ensminger, Stephan; Vlachojannis, Marios; Birschmann, Ingvild

    2016-09-01

    The occurrence of lupus anticoagulant is associated with the hazard of developing an antiphospholipid syndrome, a severe prothrombotic condition which may particularly occur after major surgical trauma. This disease requires certain considerations regarding surgical strategy and anticoagulation management. We describe the perioperative management of a patient scheduled for elective aortic valve replacement and diagnosed for having antiphospholipid antibodies. The procedure was successfully performed using a minimally invasive approach via transapical aortic valve replacement and anticoagulation with the nonreversible short-acting direct thrombin Inhibitor bivalirudin.

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

    PubMed

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

    2014-04-01

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

  3. Bivalirudin anticoagulation for minimal invasive transapical transcatheter aortic valve replacement in a patient with antiphospholipid antibodies.

    PubMed

    Koster, Andreas; Ensminger, Stephan; Vlachojannis, Marios; Birschmann, Ingvild

    2016-09-01

    The occurrence of lupus anticoagulant is associated with the hazard of developing an antiphospholipid syndrome, a severe prothrombotic condition which may particularly occur after major surgical trauma. This disease requires certain considerations regarding surgical strategy and anticoagulation management. We describe the perioperative management of a patient scheduled for elective aortic valve replacement and diagnosed for having antiphospholipid antibodies. The procedure was successfully performed using a minimally invasive approach via transapical aortic valve replacement and anticoagulation with the nonreversible short-acting direct thrombin Inhibitor bivalirudin. PMID:27555195

  4. Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension.

    PubMed

    Cirulis, Meghan M; Ryan, John J

    2016-05-01

    The use of anticoagulation as part of the treatment regimen in pulmonary arterial hypertension (PAH) remains a topic of debate. A recently published analysis of anticoagulation use in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) study offers conflicting conclusions regarding the benefit of this therapeutic strategy. There remains no robust randomized trial in PAH weighing the risks versus benefits of including anticoagulation in treatment regimens, leaving clinicians to surmise value in individual patients. Reexamination of available data may help to provide guidance on this controversial topic in the absence of future dedicated investigations. PMID:27162687

  5. Oral anticoagulation in elderly patients as secondary prevention of cardioembolic strokes

    PubMed Central

    2010-01-01

    Background Stroke incidence increases with age. Atrial fibrillation (AF) is an important risk factor for ischemic stroke and its incidence also increases with age. However oral anticoagulant therapy (OAT) tends to be underused in the elderly population. Methods Elderly patients (> = 80 years) with an ischemic stroke admitted in our department between 1/7/2003 and 31/6/2005 were prospectively evaluated. Baseline characteristics, risk factors, treatment and etiology according to TOAST criteria were recorded. Patients treated with OAT were followed up in order to assess any side effect and stroke recurrence. Mean follow-up was of 19.5 months (7-45) from discharge. Results Sixty four out of a hundred and fifty nine elderly patients (40.25%) were classified as cardioembolic; mean age was 84.5 years (80-97) and 64.6% were women. AF had been previously identified in 60% of them (16.9% were on OAT and 40.6% on antiplatelet therapy). At discharge, 32 patients (49.2%) were on OAT. In the follow-up 4 patients (12.5%) suffered systemic haemorrhages (3 urinary, 1 gastrointestinal bleeding), with no change in their functional status. Mean INR in this group was 5.9 [3-11] and, in 3 of them, OAT was cancelled. No brain haemorrhages were recorded. Ischemic stroke recurred in 4 patients (INR < 1.8 in 3 of them; the other, INR 2.35). Three patients had died at the end of the follow-up, one of them as a consequence of ischemic stroke recurrence. Discussion Twenty eight point eight of stroke patients admitted in the period of study were >80 years. The high proportion of cardioembolic strokes in this age segment contrasts with the general underuse of OAT as antithrombotic prophylaxis. Our study suggests that OAT is a safe strategy when carefully prescribed, even for elderly patients. PMID:20525389

  6. Targeting clotting proteins in cancer therapy - progress and challenges.

    PubMed

    Ruf, Wolfram; Rothmeier, Andrea S; Graf, Claudine

    2016-04-01

    Cancer-associated thrombosis remains a significant complication in the clinical management of cancer and interactions of the hemostatic system with cancer biology continue to be elucidated. Here, we review recent progress in our understanding of tissue factor (TF) regulation and procoagulant activation, TF signaling in cancer and immune cells, and the expanding roles of the coagulation system in stem cell niches and the tumor microenvironment. The extravascular functions of coagulant and anti-coagulant pathways have significant implications not only for tumor progression, but also for the selection of appropriate target specific anticoagulants in the therapy of cancer patients. PMID:27067961

  7. The Prototype Compound for the Oral Anticoagulants: 3,3'-Methylene bis(4-hydroxycoumarin).

    ERIC Educational Resources Information Center

    Hayward, Rodney C.

    1984-01-01

    Provides background information on the development and action of the coumarin family of anticoagulants, focusing on an experimental procedure for the synthesis of dicumerol. Includes procedures used and safety considerations. (JM)

  8. Bleeding Risk, Management and Outcome in Patients Receiving Non-VKA Oral Anticoagulants (NOACs).

    PubMed

    Werth, Sebastian; Breslin, Tomás; NiAinle, Fionnuala; Beyer-Westendorf, Jan

    2015-08-01

    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

  9. Anticoagulant rodenticide exposure and toxicosis in coyotes (Canis latrans) in the Denver Metropolitan Area.

    PubMed

    Poessel, Sharon A; Breck, Stewart W; Fox, Karen A; Gese, Eric M

    2015-01-01

    Anticoagulant rodenticides are widely used in urban areas to control rodent pests and are responsible for secondary poisoning in many nontarget wildlife species. We tested the livers of five coyotes (Canis latrans) in the Denver Metropolitan Area, Colorado, US, for anticoagulant rodenticides. All five livers were positive for brodifacoum, with values ranging from 95 ppb to 320 ppb, and one liver was positive for bromadiolone, with a value of 885 ppb. Both of these rodenticides are second-generation anticoagulants, which are more potent and more likely to cause secondary poisoning than first-generation anticoagulants due to their accumulation and persistence in the liver. We concluded that exposure to these rodenticides may have caused the death of at least two of the five coyotes, and urban coyotes in our study area are commonly exposed to rodenticides.

  10. Congenital Malformations Associated with the Administration of Oral Anticoagulants During Pregnancy

    ERIC Educational Resources Information Center

    Pettifor, J. M.; Benson, R.

    1975-01-01

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

  11. Reversed-phase HPLC determination of eight anticoagulant rodenticides in animal liver.

    PubMed

    Fauconnet, V; Pouliquen, H; Pinault, L

    1997-01-01

    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

  12. Multicomponent determination of 4-hydroxycoumarin anticoagulant rodenticides in blood serum by liquid chromatography with fluorescence detection.

    PubMed

    Felice, L J; Chalermchaikit, T; Murphy, M J

    1991-01-01

    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

  13. Multiresidue analysis of seven anticoagulant rodenticides by high-performance liquid chromatography/electrospray/mass spectrometry.

    PubMed

    Marek, LeEtta J; Koskinen, William C

    2007-02-01

    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, multiresidue method, which provides positive confirmation for both classes of anticoagulant rodenticides, is needed by diagnostic laboratories. A method was developed for the determination of seven anticoagulant rodenticides, coumafuryl, pindone, warfarin, diphacinone, chlorophacinone, bromadiolone, and brodifacoum, in diverse matrices, animal feed, cooked beef, and fruit-flavored beverages using high-performance liquid chromatography/electrospray/mass spectrometry. Detection was by MS/MS with electrospray ionization in negative mode. Confirmation was by retention time, m/z of molecular ion, and two parent-daughter transitions. Recoveries from selected the matrices ranged from 61 to 117%. Limits of quantitation were as low as 1.5-4.5 ng g-1. The developed method was rapid and provided the simultaneous confirmation and quantification of the seven anticoagulant rodenticides. PMID:17263443

  14. Anticoagulant rodenticide exposure and toxicosis in coyotes (Canis latrans) in the Denver Metropolitan Area.

    PubMed

    Poessel, Sharon A; Breck, Stewart W; Fox, Karen A; Gese, Eric M

    2015-01-01

    Anticoagulant rodenticides are widely used in urban areas to control rodent pests and are responsible for secondary poisoning in many nontarget wildlife species. We tested the livers of five coyotes (Canis latrans) in the Denver Metropolitan Area, Colorado, US, for anticoagulant rodenticides. All five livers were positive for brodifacoum, with values ranging from 95 ppb to 320 ppb, and one liver was positive for bromadiolone, with a value of 885 ppb. Both of these rodenticides are second-generation anticoagulants, which are more potent and more likely to cause secondary poisoning than first-generation anticoagulants due to their accumulation and persistence in the liver. We concluded that exposure to these rodenticides may have caused the death of at least two of the five coyotes, and urban coyotes in our study area are commonly exposed to rodenticides. PMID:25380355

  15. Prevention of thromboses in human patients with Bothrops lanceolatus envenoming in Martinique: failure of anticoagulants and efficacy of a monospecific antivenom. Research Group on Snake Bites in Martinique.

    PubMed

    Thomas, L; Tyburn, B; Bucher, B; Pecout, F; Ketterle, J; Rieux, D; Smadja, D; Garnier, D; Plumelle, Y

    1995-05-01

    Envenomation by the Bothrops lanceolatus, a snake found only in Martinique, leads to swelling and pain, and occasionally to systemic signs and/or coagulopathy. Severe thromboses at some distance from the site of the bite may appear within 48 hr. Uncertainties as to the actual development of thrombotic complications in patients appearing to be suffering from moderate poisoning and as to the availability and the toxicity of a monospecific antivenom (AVS) initially led us to reserve antivenom for the most severe cases, and to use anticoagulants to prevent thromboses in all patients. This approach was modified after we observed serious thromboses in patients with moderate poisoning. Of 50 adult snake bite cases hospitalized between June 1991 and August 1994, 11 developed serious thrombotic complications at 36 /+- 27 hr (mean +/- SD) (range 12-96) following envenomation, despite early preventive anticoagulant therapy. Those included pulmonary embolism (two cases), cerebral infarction (six cases), myocardial infarction (one case), and cerebral and myocardial infarctions (two cases). Sixteen patients were not treated with AVS: 10 of these recovered without complications and six developed systemic thrombosis causing permanent disability in three cases. Thirty were treated with an intravenous infusion of 2-6 vials of AVS given 2-48 hr after the bite. Of these, three died of cerebral infarction that developed before the initiation of serotherapy. All others recovered. Among patients treated with AVS, three presented with mild anaphylactic reactions, while one developed serum sickness that responded to steroids. These data indicate that preventive anticoagulant therapy is of limited efficacy in Martinique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7771608

  16. Structure-function relationships and mechanism of anticoagulant phospholipase A2 enzymes from snake venoms.

    PubMed

    Kini, R Manjunatha

    2005-06-15

    Phospholipase A(2) (PLA(2)) enzymes from snake venom are toxic and induce a wide spectrum of pharmacological effects, despite similarity in primary, secondary and tertiary structures and common catalytic properties. Thus, the structure-function relationships and the mechanism of this group of small proteins are subtle, complex and intriguing challenges. This review, taking the PLA(2) enzymes from spitting cobra (Naja nigricollis) venom as examples, describes the mechanism of anticoagulant effects. The strongly anticoagulant CM-IV inhibits both the extrinsic tenase and prothrombinase complexes, whereas the weakly anticoagulant PLA(2) enzymes (CM-I and CM-II) inhibit only the extrinsic tenase complex. CM-IV binds to factor Xa and interferes in its interaction with factor Va and the formation of prothrombinase complex. In contrast, CM-I and CM-II do not affect the formation of prothrombinase complex. In addition, CM-IV inhibits the extrinsic tenase complex by a combination of enzymatic and nonenzymatic mechanisms, while CM-I and CM-II inhibit by only enzymatic mechanism. These functional differences explain the disparity in the anticoagulant potency of N. nigricollis PLA(2) enzymes. Similarly, human secretory enzyme binds to factor Xa and inhibits the prothrombinase complex. We predicted the anticoagulant region of PLA(2) enzymes using a systematic and direct comparison of amino acid sequences. This region between 54 and 77 residues is basic in the strongly anticoagulant PLA(2) enzymes and neutral or negatively charged in weakly and non-anticoagulant enzymes. The prediction is validated independently by us and others using both site directed mutagenesis and synthetic peptides. Thus, strongly anticoagulant CM-IV binds to factor Xa (its target protein) through the specific anticoagulant site on its surface. In contrast, weakly anticoagulant enzymes, which lack the anticoagulant region fail to bind specifically to the target protein, factor Xa in the coagulation cascade

  17. Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives.

    PubMed

    Abdelhafez, Omaima M; Amin, Kamelia M; Batran, Rasha Z; Maher, Timothy J; Nada, Somaia A; Sethumadhavan, Shalini

    2010-05-15

    The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulant study with respect to warfarin showed that the synthesized compounds have different anticoagulant activities, the most prospective compounds were the 3-pyrazolyl-4-hydroxycoumarin derivatives.

  18. Referral of patients to an anticoagulant clinic: implications for better management.

    PubMed

    Tan, G B; Cohen, H; Taylor, F C; Gabbay, J

    1993-06-01

    The quality of anticoagulant treatment of ambulatory patients is affected by the content of referral letters and administrative processes. To assess these influences a method was developed to audit against the hospital standard the referral of patients to one hospital anticoagulant clinic in a prospective study of all (80) new patients referred to the clinic over eight months. Administrative information was provided by the clinic coordinator, and the referral letters were audited by the researchers. Referral letters were not received by the clinic for 10% (8/80) of patients. Among the 72 referral letters received, indication for anticoagulation and anticipated duration of treatment were specified in most (99%, 71 and 81%, 58 respectively), but only 3% (two) to 46% (33) reported other important clinical information (objective investigations, date of starting anticoagulation, current anticoagulant dose, date and result of latest international normalised ratio, whether it should be the anticoagulant clinic that was eventually to stop anticoagulation, patients' other medical problems and concurrent treatment. Twenty two per cent (16/80) of new attenders were unexpected at the anticoagulant clinic. Most patients' case notes were obtained for the appointment (61%, 47/77 beforehand and 30% 23/77 on the day), but case notes were not obtained for 9% (7/77). The authors conclude that health professionals should better appreciate the administrative and organisational influences that affect team work and quality of care. Compliance with a well documented protocol remained below the acceptable standard. The quality of the referral process may be improved by using a more comprehensive and helpful referral form, which has been drawn up, and by educating referring doctors. Measures to increase the efficiency of the administrative process include telephoning the clinic coordinator directly, direct referrals through a computerised referral system, and telephone reminders by

  19. New oral anticoagulants: their role in stroke prevention in high-risk patients with atrial fibrillation.

    PubMed

    Ferns, Sunita J; Naccarelli, Gerald V

    2015-07-01

    Based on efficacy, safety, and ease of use, novel oral anticoagulants will likely replace VKAs for many if not most patients with atrial fibrillation. Novel anticoagulants have a lower rate of intracranial hemorrhage compared with vitamin K antagonists. The incidence of other life-threatening bleeds is similar if not lower. Dose adjustments need to be made based on renal function and advanced age. There is at present a need for an antidote for these new drugs.

  20. A rapid pro-hemostatic approach to overcome direct oral anticoagulants.

    PubMed

    Thalji, Nabil K; Ivanciu, Lacramioara; Davidson, Robert; Gimotty, Phyllis A; Krishnaswamy, Sriram; Camire, Rodney M

    2016-08-01

    Direct inhibitors of coagulation factor Xa (FXa) or thrombin are promising oral anticoagulants that are becoming widely adopted. The ability to reverse their anticoagulant effects is important when serious bleeding occurs or urgent medical procedures are needed. Here, using experimental mouse models of hemostasis, we show that a variant coagulation factor, FXa(I16L), rapidly restores hemostasis in the presence of the anticoagulant effects of these inhibitors. The ability of FXa(I16L) to reverse the anticoagulant effects of FXa inhibitor depends, at least in part, on the ability of the active site inhibitor to hinder antithrombin-dependent FXa inactivation, paradoxically allowing uninhibited FXa to persist in plasma. Because of its inherent catalytic activity, FXa(I16L) is more potent (by >50-fold) in the hemostasis models tested than a noncatalytic antidote that is currently in clinical development. FXa(I16L) also reduces the anticoagulant-associated bleeding in vivo that is induced by the thrombin inhibitor dabigatran. FXa(I16L) may be able to fill an important unmet clinical need for a rapid, pro-hemostatic agent to reverse the effects of several new anticoagulants. PMID:27455511

  1. Anticoagulation policy after venous resection with a pancreatectomy: a systematic review

    PubMed Central

    Chandrasegaram, Manju D; Eslick, Guy D; Lee, Wayne; Brooke-Smith, Mark E; Padbury, Rob; Worthley, Christopher S; Chen, John W; Windsor, John A

    2014-01-01

    Background Portal vein (PV) resection is used increasingly in pancreatic resections. There is no agreed policy regarding anticoagulation. Methods A systematic review was performed to compare studies with an anticoagulation policy (AC+) to no anticoagulation policy (AC−) after venous resection. Results There were eight AC+ studies (n = 266) and five AC− studies (n = 95). The AC+ studies included aspirin, clopidogrel, heparin or warfarin. Only 50% of patients in the AC+ group received anticoagulation. There were more prosthetic grafts in the AC+ group (30 versus 2, Fisher's exact P < 0.001). The overall morbidity and mortality was similar in both groups. Early PV thrombosis (EPVT) was similar in the AC+ group and the AC− group (7%, versus 3%, Fisher's exact P = 0.270) and was associated with a high mortality (8/20, 40%). When prosthetic grafts were excluded there was no difference in the incidence of EPVT between both groups (1% vs 2%, Fisher's exact test P = 0.621). Conclusion There is significant heterogeneity in the use of anticoagulation after PV resection. Overall morbidity, mortality and EPVT in both groups were similar. EPVT has a high associated mortality. While we have been unable to demonstrate a benefit for anticoagulation, the incidence of EPVT is low in the absence of prosthetic grafts. PMID:24344986

  2. Occurrence, elimination, and risk of anticoagulant rodenticides and drugs during wastewater treatment.

    PubMed

    Gómez-Canela, Cristian; Barata, Carlos; Lacorte, Silvia

    2014-01-01

    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

  3. Use and Safety of Unfractionated Heparin for Anticoagulation During Maintenance Hemodialysis

    PubMed Central

    Shen, Jenny I.; Winkelmayer, Wolfgang C.

    2014-01-01

    Anticoagulation is essential to hemodialysis, and unfractionated heparin (UFH) is the most commonly used anticoagulant in the United States. However, there is no universally accepted standard for its administration in long-term hemodialysis. Dosage schedules vary and include weight-based protocols and low-dose protocols for those at high risk of bleeding, as well as regional anticoagulation with heparin and heparin-coated dialyzers. Adjustments are based largely on clinical signs of under- and overanticoagulation. Risks of UFH use include bleeding, heparin-induced thrombocytopenia, hypertriglyceridemia, anaphylaxis, and possibly bone mineral disease, hyperkalemia, and catheter-associated sepsis. Alternative anticoagulants include low-molecular-weight heparin, direct thrombin inhibitors, heparinoids, and citrate. Anticoagulant-free hemodialysis and peritoneal dialysis also are potential substitutes. However, some of these alternative treatments are not as available as or are more costly than UFH, are dependent on country and health care system, and present dosing challenges. When properly monitored, UFH is a relatively safe and economical choice for anticoagulation in long-term hemodialysis for most patients. PMID:22560830

  4. Diversity and selective pressures of anticoagulants in three medicinal leeches (Hirudinida: Hirudinidae, Macrobdellidae).

    PubMed

    Kvist, Sebastian; Min, Gi-Sik; Siddall, Mark E

    2013-04-01

    Although medicinal leeches have long been used as treatment for various ailments because of their potent anticoagulation factors, neither the full diversity of salivary components that inhibit coagulation, nor the evolutionary selection acting on them has been thoroughly investigated. Here, we constructed expressed sequence tag libraries from salivary glands of two species of medicinal hirudinoid leeches, Hirudo verbana and Aliolimnatis fenestrata, and identified anticoagulant-orthologs through BLASTx searches. The data set then was augmented by the addition of a previously constructed EST library from the macrobdelloid leech Macrobdella decora. The identified orthologs then were compared and contrasted with well-characterized anticoagulants from a variety of leeches with different feeding habits, including non-sanguivorous species. Moreover, four different statistical methods for predicting signatures of positive and negative evolutionary pressures were used for 10 rounds each to assess the level and type of selection acting on the molecules as a whole and on specific sites. In total, sequences showing putative BLASTx-orthology with five and three anticoagulant-families were recovered in the A. fenestrata and H. verbana EST libraries respectively. Selection pressure analyses predicted high levels of purifying selection across the anticoagulant diversity, although a few isolated sites showed signatures of positive selection. This study represents a first attempt at mapping the anticoagulant repertoires in a comparative fashion across several leech families.

  5. New oral anticoagulants: clinical indications, monitoring and treatment of acute bleeding complications.

    PubMed

    Fenger-Eriksen, C; Münster, A-M; Grove, E L

    2014-07-01

    New oral anticoagulants like the direct thrombin inhibitor, dabigatran (Pradaxa®), and factor Xa-inhibitors, rivaroxaban (Xarelto®) and apixaban (Eliquis®) are available for prophylaxis and treatment of thromboembolic disease. They are emerging alternatives to warfarin and provide equal or better clinical outcome together with reduced need for routine monitoring. Methods for measuring drug concentrations are available, although a correlation between plasma drug concentrations and the risk of bleeding has not been firmly established. Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants. Thus, these standard tests may only be used as a crude estimation of the actual anticoagulation status. Further challenges regarding patients receiving new oral anticoagulants who presents with major bleeding or need for emergency surgery pose a unique problem. No established agents are clinically available to reverse the anticoagulant effect, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents. This review summaries current knowledge on approved new oral anticoagulants and discusses clinical aspects of monitoring, with particular focus on the management of the bleeding patient.

  6. A New Pharmacogenetic Algorithm to Predict the Most Appropriate Dosage of Acenocoumarol for Stable Anticoagulation in a Mixed Spanish Population.

    PubMed

    Tong, Hoi Y; Dávila-Fajardo, Cristina Lucía; Borobia, Alberto M; Martínez-González, Luis Javier; Lubomirov, Rubin; Perea León, Laura María; Blanco Bañares, María J; Díaz-Villamarín, Xando; Fernández-Capitán, Carmen; Cabeza Barrera, José; Carcas, Antonio J

    2016-01-01

    There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (<11 mg/week, 11-21 mg/week, >21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in

  7. The optimal management of patients on oral anticoagulation undergoing coronary artery stenting. The 10th Anniversary Overview.

    PubMed

    Rubboli, A; Faxon, D P; Juhani Airaksinen, K E; Schlitt, A; Marín, F; Bhatt, D L; Lip, G Y H

    2014-12-01

    Even 10 years after the first appearance in the literature of articles reporting on the management of patients on oral anticoagulation (OAC) undergoing percutaneous coronary intervention with stent (PCI-S), this issue is still controversial. Nonetheless, some guidance for the everyday management of this patient subset, accounting for about 5-8 % of all patients referred for PCI-S, has been developed. In general, a period of triple therapy (TT) of OAC, with either vitamin K-antagonists (VKA) or non-vitamin K-antagonist oral anticoagulants (NOAC), aspirin, and clopidogrel is warranted, followed by the combination of OAC, and a single antiplatelet agent for up to 12 months, and then OAC alone. The duration of the initial period of TT is dependent on the individual risk of thromboembolism, and bleeding, as well as the clinical context in which PCI-S is performed (elective vs acute coronary syndrome), and the type of stent implanted (bare-metal vs drug-eluting). In this article, we aim to provide a comprehensive, at-a-glance, overview of the management strategies, which are currently suggested for the peri-procedural, medium-term, and long-term periods following PCI-S in OAC patients. While acknowledging that most of the evidence has been obtained from patients on OAC because of atrial fibrillation, and with warfarin being the most frequently used VKA, we refer in this overview to the whole population of OAC patients undergoing PCI-S. We refer to the whole population of patients on OAC undergoing PCI-S also when OAC is carried out with NOAC rather than VKA, pointing out, when appropriate, the particular management issues.

  8. Poisoning of wildlife with anticoagulant rodenticides in New York.

    PubMed

    Stone, W B; Okoniewski, J C; Stedelin, J R

    1999-04-01

    From 1971 through 1997, we documented 51 cases (55 individual animals) of poisoning of non-target wildlife in New York (plus two cases in adjoining states) (USA) with anticoagulant rodenticides--all but two of these cases occurred in the last 8 yrs. Brodifacoum was implicated in 80% of the incidents. Diphacinone was identified in four cases, bromadiolone in three cases (once in combination with brodifacoum), and chlorophacinone and coumatetralyl were detected once each in the company of brodifacoum. Warfarin accounted for the three cases documented prior to 1989, and one case involving a bald eagle (Haliaeetus leucocephalus) in 1995. Secondary intoxication of raptors, principally great horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis), comprised one-half of the cases. Gray squirrels (Sciurus carolinensis), raccoons (Procyon lotor) and white-tailed deer (Odocoileus virginianus) were the most frequently poisoned mammals. All of the deer originated from a rather unique situation on a barrier island off southern Long Island (New York). Restrictions on the use of brodifacoum appear warranted. PMID:10231745

  9. Overview of the new oral anticoagulants: opportunities and challenges.

    PubMed

    Yeh, Calvin H; Hogg, Kerstin; Weitz, Jeffrey I

    2015-05-01

    The non-vitamin K antagonist oral anticoagulants (NOACs) are replacing warfarin for many indications. These agents include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. All 4 agents are licensed in the United States for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism and rivaroxaban and apixaban are approved for thromboprophylaxis after elective hip or knee arthroplasty. The NOACs are at least as effective as warfarin, but are not only more convenient to administer because they can be given in fixed doses without routine coagulation monitoring but also are safer because they are associated with less intracranial bleeding. As part of a theme series on the NOACs, this article (1) compares the pharmacological profiles of the NOACs with that of warfarin, (2) identifies the doses of the NOACs for each approved indication, (3) provides an overview of the completed phase III trials with the NOACs, (4) briefly discusses the ongoing studies with the NOACs for new indications, (5) reviews the emerging real-world data with the NOACs, and (6) highlights the potential opportunities for the NOACs and identifies the remaining challenges. PMID:25792448

  10. Hypertension and Atrial Fibrillation: Any Change with the New Anticoagulants.

    PubMed

    Ghiadoni, Lorenzo; Taddei, Stefano; Virdis, Agostino

    2014-01-01

    Hypertension and atrial fibrillation are the most common cardiovascular risk factors and clinically significant arrhythmia, respectively. These conditions frequently coexist and their prevalence increases rapidly with aging. Despite several different risk factors and clinical conditions predisposing to hypertension for its high prevalence in the population is still the main risk factor for the development of atrial fibrillation. Several pathophysiologic mechanisms (such as structural changes at the level of left ventricle and or atrium, neurohormonal activation, arterial stiffness, etc.) can contribute to the onset of atrial fibrillation. Some antihypertensive treatments have been shown to contribute to reduce the risk of new-onset atrial fibrillation. Atrial fibrillation is a major risk factor for stroke, which is further increased in the presence of hypertension. For this reason, hypertension is included as a major risk factor in the available models for the risk stratification and the prevention of thromboembolism in patients with atrial fibrillation. In this article we will review the relationship between atrial fibrillation and hypertension, looking at the possible specific indications of the antithrombotic treatment with new classes of anticoagulants in the prevention of thromboembolic events in hypertensive patients with atrial fibrillation.

  11. Synthesis and Anticoagulant Activity of Polyureas Containing Sulfated Carbohydrates

    PubMed Central

    2015-01-01

    Polyurea-based synthetic glycopolymers containing sulfated glucose, mannose, glucosamine, or lactose as pendant groups have been synthesized by step-growth polymerization of hexamethylene diisocyanate and corresponding secondary diamines. The obtained polymers were characterized by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. The nonsulfated polymers showed similar results to the commercially available biomaterial polyurethane TECOFLEX in a platelet adhesion assay. The average degree of sulfation after reaction with SO3 was calculated from elemental analysis and found to be between three and four −OSO3 groups per saccharide. The blood-compatibility of the synthetic polymers was measured using activated partial thromboplastin time, prothrombin time, thrombin time, anti-IIa, and anti-Xa assays. Activated partial thromboplastin time, prothrombin time, and thrombin time results indicated that the mannose and lactose based polymers had the highest anticoagulant activities among all the sulfated polymers. The mechanism of action of the polymers appears to be mediated via an anti-IIa pathway rather than an anti-Xa pathway. PMID:25329742

  12. Prevalence and Resolution of Lupus Anticoagulant in Children

    PubMed Central

    Kallanagowdar, Chandra; Chauhan, Aman; Puertolas, Mora V.; Warrier, Rajasekharan

    2016-01-01

    Background: Lupus anticoagulant (LA) is an autoantibody that inhibits phospholipid-dependent reactions. Studies on the incidence and prevalence of LA in the pediatric population are lacking. The objective of our study was to determine the incidence and potential risk of complications of LA in children presenting with abnormal partial thromboplastin time (PTT). Our secondary objective was to identify signs, symptoms, and medical history associated with the presence of LA as documented in the literature. We focused on the correlation between signs of LA in the form of laboratory values consistent with bleeding abnormalities and the presence of clinical symptoms of bleeding. Methods: We conducted a record-based retrospective analysis of 112 children and adolescents referred to the Department of Hematology/Oncology at Children's Hospital of New Orleans for abnormal coagulation profiles and/or history of mucocutaneous bleeding. Participants were followed up until PTT values normalized. Results: In our study population with suspected bleeding disorder, the preliminary incidence of LA was 21%. We found that resolution of LA correlated with correction of PTT in 90% of patients. Conclusion: To minimize extensive and expensive blood workup, we recommend that screening for LA be included in the evaluation of children with prolonged PTT, even if they have a negative history of bleeding problems. PMID:27303229

  13. Optimal Anticoagulation during Off Pump Coronary Artery Bypass in Patients Recently Exposed to Clopidogrel

    PubMed Central

    Song, Young; Song, Jong Wook; Shim, Jae Kwang

    2013-01-01

    Purpose The aim of this study was to find an optimal range of activated clotting time (ACT) during off-pump coronary artery bypass surgery (OPCAB) yielding ischemic protection without the risk of hemorrhagic complications in patients with recent exposure to dual antiplatelet therapy. Materials and Methods Three hundred and five patients who received aspirin and clopidogrel within 7 days of isolated multi-vessel OPCAB were retrospectively studied. Combined hemorrhagic and ischemic outcome was defined as the occurrence of 1 of the following: significant perioperative bleeding (>30% of estimated blood volume), transfusion of packed red blood cell (pRBC) ≥2 U, or myocardial infarction (MI). This was compared in relation to the tertile distribution of the time-weighted average ACT-212-291 sec (first tertile), 292-334 sec (second tertile), 335-485 sec (third tertile). Results The amount of perioperative blood loss was 937±313 mL, 1014±340 mL, and 1076±383 mL, respectively (p=0.022). Significantly more patients in the third tertile developed MI (4%, 4%, and 12%, respectively, p=0.034). The incidence of significant perioperative blood loss and transfusion of pRBC ≥2 U were lower in the first tertile than those of other tertiles without statistical significance. In the multivariate analysis, the first tertile was associated with a 52% risk reduction of combined hemorrhagic and ischemic outcomes (95% confidence interval: 0.25-0.92, p=0.027). Conclusion A lower degree of anticoagulation with a reduced initial heparin loading dose should be carefully considered for patients undergoing OPCAB who have recently been exposed to clopidogrel. PMID:23918560

  14. Monitoring oral anticoagulant treatment with the TAS near-patient test system: comparison with conventional thromboplastins.

    PubMed Central

    Kitchen, S; Preston, F E

    1997-01-01

    BACKGROUND: A number of instruments have been developed for determination of prothrombin time (PT) and International Normalised Ratio (INR) at locations not limited to central laboratories. AIM: To evaluate one such portable instrument, the Thrombolytic Assessment System (TAS), which can be used in a near-patient setting. METHODS: Samples from 20 normal subjects and 48 patients treated with warfarin for venous thromboembolic disease were studied. The warfarin group was divided into: initiation phase (n = 10), combined warfarin and heparin (n = 10), stabilised therapy (n = 20), and over anticoagulated patients (n = 8). PTs and INRs were determined in each group using three conventional thromboplastins (Diagen Activated, Manchester Reagent, and Instrumentation Laboratory) and two TAS techniques (whole blood or plasma). An independent International Sensitivity Index (ISI) calibration of the TAS system was performed. RESULTS: Calculated ISIs for the TAS were 1.028 and 0.984 for plasma and whole blood analysis, respectively, compared with manufacturer's values of 0.98 and 0.97. INR results with TAS (whole blood) were 11% less than those obtained with Diagen Activated (p < 0.01) and 16% less than those obtained with Instrumentation Laboratory (p < 0.001) when manufacturers' mean normal PT and ISI were used for TAS INRs. TAS (whole blood) results were similar to TAS plasma or Manchester Reagent results. The use of a locally determined mean normal prothrombin time (MNPT) improved agreement between TAS and the other reagents, abolishing the significant difference between INRs determined with TAS (whole blood) and Diagen Activated techniques. CONCLUSION: The TAS system can be used with whole blood or plasma and produces similar INRs to those obtained with Diagen Activated or Manchester Reagent using manufacturer's ISI and a locally determined MNPT. Results were lower with TAS or Manchester Reagent compared with those obtained with Instrumentation Laboratory thromboplastin

  15. Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers.

    PubMed

    Peacock, W Frank

    2014-10-01

    The therapeutic landscape for anticoagulation management is undergoing a shift from the use of traditional anticlotting agents such as heparins and warfarin as the only options to the growing adoption of newer target-specific oral anticoagulants (TSOACs) with novel mechanisms of action. Dabigatran, the first TSOAC approved for use in the United States, is a direct competitive inhibitor of thrombin. It has predictable kinetics, with an elimination half-life of 12 to 17 hours in healthy volunteers. Apixaban and rivaroxaban are selective inhibitors of factor Xa, and also display first-order kinetics. In younger healthy individuals, apixaban has an apparent half-life of approximately 12 hours, whereas rivaroxaban has an elimination half-life of 5 to 9 hours. Understanding the pharmacologic properties of these newer drugs can lead to better insights regarding their respective safety and efficacy profiles and their application in clinical practice. Laboratory assessments have been developed to measure the anticoagulant efficacy of these newer agents. However, the results of these tests can be highly variable, and are therefore not always useful for monitoring the anticoagulation effects of these agents. In addition, several strategies have been documented for the potential reversal of the anticoagulant effects of these drugs, from the temporary discontinuation of an agent before elective surgery to suggested emergency procedures in the case of major bleeding events. New, specific reversal agents for dabigatran, apixaban, and rivaroxaban are currently being developed, and dabigatran has received fast-track designation from the US Food and Drug Administration. Until comprehensive clinical guidelines are developed, institutions involved in emergency care should establish their own procedures for the management of patients undergoing anticoagulation who require emergency treatment. These protocols should include appropriate laboratory testing to assess anticoagulant activity

  16. Managing bleeding and emergency reversal of newer oral anticoagulants: a review for primary care providers.

    PubMed

    Peacock, W Frank

    2014-10-01

    The therapeutic landscape for anticoagulation management is undergoing a shift from the use of traditional anticlotting agents such as heparins and warfarin as the only options to the growing adoption of newer target-specific oral anticoagulants (TSOACs) with novel mechanisms of action. Dabigatran, the first TSOAC approved for use in the United States, is a direct competitive inhibitor of thrombin. It has predictable kinetics, with an elimination half-life of 12 to 17 hours in healthy volunteers. Apixaban and rivaroxaban are selective inhibitors of factor Xa, and also display first-order kinetics. In younger healthy individuals, apixaban has an apparent half-life of approximately 12 hours, whereas rivaroxaban has an elimination half-life of 5 to 9 hours. Understanding the pharmacologic properties of these newer drugs can lead to better insights regarding their respective safety and efficacy profiles and their application in clinical practice. Laboratory assessments have been developed to measure the anticoagulant efficacy of these newer agents. However, the results of these tests can be highly variable, and are therefore not always useful for monitoring the anticoagulation effects of these agents. In addition, several strategies have been documented for the potential reversal of the anticoagulant effects of these drugs, from the temporary discontinuation of an agent before elective surgery to suggested emergency procedures in the case of major bleeding events. New, specific reversal agents for dabigatran, apixaban, and rivaroxaban are currently being developed, and dabigatran has received fast-track designation from the US Food and Drug Administration. Until comprehensive clinical guidelines are developed, institutions involved in emergency care should establish their own procedures for the management of patients undergoing anticoagulation who require emergency treatment. These protocols should include appropriate laboratory testing to assess anticoagulant activity

  17. Early prophylactic anticoagulation for portal vein system thrombosis after splenectomy: A systematic review and meta-analysis

    PubMed Central

    Zhang, Ning; Yao, Yingmin; Xue, Wanli; Wu, Shengli

    2016-01-01

    A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of early prophylactic anticoagulation for the prevention of portal vein system thrombosis (PVST) after splenectomy. A systematic search of the PubMed, EMBASE, Springer and Cochrane Library databases was performed to identify studies comparing the outcomes in patients receiving or not receiving regular prophylactic anticoagulation after splenectomy. The quality of the included studies was assessed using the Jadad Score and the Newcastle-Ottawa Scale. Heterogeneity was evaluated using the χ2 and I2 tests. The parameters that were analyzed included the incidence of PVST and anticoagulation-associated complications. A total of seven studies qualified for the review, involving 383 and 283 patients receiving or not receiving regular prophylactic anticoagulation, respectively. The incidence of PVST was significantly reduced with an odds ratio (OR) of 0.31 [95% confidence interval (CI), 0.21–0.46; P<0.00001] in the regular prophylactic anticoagulation group compared with the control group. No difference in the incidence of anticoagulation-associated complications was identified between the two groups (OR=0.60, 95% CI, 0.23–1.56; P=0.30). Early prophylactic anticoagulation was associated with a reduced incidence of PVST, although it was not associated with the incidence of anticoagulation-associated complications. These results indicate that prophylactic anticoagulation could be safely administered after splenectomy, even to cirrhotic patients.

  18. Early prophylactic anticoagulation for portal vein system thrombosis after splenectomy: A systematic review and meta-analysis

    PubMed Central

    Zhang, Ning; Yao, Yingmin; Xue, Wanli; Wu, Shengli

    2016-01-01

    A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of early prophylactic anticoagulation for the prevention of portal vein system thrombosis (PVST) after splenectomy. A systematic search of the PubMed, EMBASE, Springer and Cochrane Library databases was performed to identify studies comparing the outcomes in patients receiving or not receiving regular prophylactic anticoagulation after splenectomy. The quality of the included studies was assessed using the Jadad Score and the Newcastle-Ottawa Scale. Heterogeneity was evaluated using the χ2 and I2 tests. The parameters that were analyzed included the incidence of PVST and anticoagulation-associated complications. A total of seven studies qualified for the review, involving 383 and 283 patients receiving or not receiving regular prophylactic anticoagulation, respectively. The incidence of PVST was significantly reduced with an odds ratio (OR) of 0.31 [95% confidence interval (CI), 0.21–0.46; P<0.00001] in the regular prophylactic anticoagulation group compared with the control group. No difference in the incidence of anticoagulation-associated complications was identified between the two groups (OR=0.60, 95% CI, 0.23–1.56; P=0.30). Early prophylactic anticoagulation was associated with a reduced incidence of PVST, although it was not associated with the incidence of anticoagulation-associated complications. These results indicate that prophylactic anticoagulation could be safely administered after splenectomy, even to cirrhotic patients. PMID:27699018

  19. Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study).

    PubMed

    Saji, Naoki; Kimura, Kazumi; Tateishi, Yohei; Fujimoto, Shigeru; Kaneko, Nobuyuki; Urabe, Takao; Tsujino, Akira; Iguchi, Yasuyuki

    2016-11-01

    The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2-4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.

  20. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  1. Suboptimal use of non-vitamin K antagonist oral anticoagulants

    PubMed Central

    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

    2016-01-01

    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

  2. Efficacy of prothrombin complex concentrates for the emergency reversal of dabigatran-induced anticoagulation.

    PubMed

    Grottke, Oliver; Aisenberg, James; Bernstein, Richard; Goldstein, Patrick; Huisman, Menno V; Jamieson, Dara G; Levy, Jerrold H; Pollack, Charles V; Spyropoulos, Alex C; Steiner, Thorsten; Del Zoppo, Gregory J; Eikelboom, John

    2016-01-01

    Dabigatran is effective in decreasing the risk of ischaemic stroke in patients with atrial fibrillation. However, like all anticoagulants, it is associated with a risk of bleeding. In cases of trauma or emergency surgery, emergency reversal of dabigatran-induced anticoagulation may be required. A specific reversal agent for dabigatran, idarucizumab, has been approved by the US Food and Drug Administration. Alternative reversal agents are available, such as prothrombin complex concentrates (PCCs) and activated PCCs (aPCCs). In this review we evaluate the role of PCCs and aPCCs in the reversal of dabigatran anticoagulation and consider which tests are appropriate for monitoring coagulation in this setting. Pre-clinical studies, small clinical studies and case reports indicate that PCCs and aPCCs may be able to reverse dabigatran-induced anticoagulation in a dose-dependent manner. However, dosing based on coagulation parameters can be difficult because available assays may not provide adequate sensitivity and specificity for measuring anticoagulation induced by dabigatran or the countering effects of PCCs/aPCCs. In addition, PCCs or aPCCs can potentially provoke thromboembolic complications. Despite these limitations and the fact that PCCs and aPCCs are not yet licensed for dabigatran reversal, their use appears to be warranted in patients with life-threatening haemorrhage if idarucizumab is not available. PMID:27125504

  3. Effect of aqueous extract and fractions of Fagonia arabica on in vitro anticoagulant activity.

    PubMed

    Chourasia, Sweta R; Kashyap, Rajpal Singh; Deopujari, Jayant Y; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F

    2014-11-01

    Fagonia arabica (FA) is a deobstruent and blood purifier, which possesses thrombolytic and antioxidant activities. In this study, the anticoagulant effects of FA and its derived fractions were evaluated. Plasma recalcification was performed with multisolvent extracts of FA and then with extracts prepared successively with increasing polarity of the solvents. Aqueous extract was the most potent anticoagulant extract, which was fractionated by thin-layer chromatography and column chromatography. Five fractions collected were checked for their anticoagulation effect. The most potent fraction was screened for phytoconstituents. Aqueous extract of FA is the most active anticoagulant (31 minutes). Results were statistically significant when compared to heparin (38 minutes) and saline (4.04 minutes; P > .001). The Fifth fraction (FA5), the most potent fraction (27 minutes), was found positive for flavonoids, saponin, tannin, triterpenoids, carbohydrates, reducing sugar, and monosaccharides. Aqueous FA and fraction FA5 were most active in in vitro anticoagulation, and any of the phytochemicals identified could be considered the active component. PMID:23814169

  4. Anticoagulant Activity of Polyphenolic-Polysaccharides Isolated from Melastoma malabathricum L.

    PubMed Central

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

    2014-01-01

    Melastoma malabathricum Linn. is a perennial traditional medicine plants that grows abundantly throughout Asian countries. In this study, M. malabathricum Linn. leaf hot water crude extract with anticoagulant activity was purified through solid phase extraction cartridge and examined for the bioactive chemical constituents on blood coagulation reaction. The SPE purified fractions were, respectively, designated as F1, F2, F3, and F4, and each was subjected to the activated partial thromboplastin time (APTT) anticoagulant assay. Active anticoagulant fractions (F1, F2, and F3) were subjected to chemical characterisation evaluation. Besides, neutral sugar for carbohydrate part was also examined. F1, F2, and F3 were found to significantly prolong the anticoagulant activities in the following order, F1 > F2 > F3, in a dose dependent manner. In addition, carbohydrate, hexuronic acid, and polyphenolic moiety were measured for the active anticoagulant fractions (F1, F2, and F3). The characterisation of chemical constituents revealed that all these three fractions contained acidic polysaccharides (rhamnogalacturonan, homogalacturonan, and rhamnose hexose-pectic type polysaccharide) and polyphenolics. Hence, it was concluded that the presence of high hexuronic acids and polysaccharides, as well as polyphenolics in traditional medicinal plant, M. malabathricum, played a role in prolonging blood clotting in the intrinsic pathway. PMID:24987430

  5. Management of anticoagulant-related intracranial hemorrhage: an evidence-based review

    PubMed Central

    2014-01-01

    The increased use of anticoagulants for the prevention and treatment of thromboembolic diseases has led to a rising incidence of anticoagulant-related intracranial hemorrhage (AICH) in the aging western population. High mortality accompanies this form of hemorrhagic stroke, and significant and debilitating long-term consequences plague survivors. Although management guidelines for such hemorrhages are available for the older generation anticoagulants, they are still lacking for newer agents, which are becoming popular among physicians. Supportive care, including blood pressure control, and reversal of anticoagulation remain the cornerstone of acute management of AICH. Prothrombin complex concentrates are gaining popularity over fresh frozen plasma, and reversal agents for newer anticoagulation agents are being developed. Surgical interventions are options fraught with complications, and are decided on a case-by-case basis. Our current state of understanding of this condition and its management is insufficient. This deficit calls for more population-based studies and therapeutic trials to better evaluate risk factors for, and to prevent and treat AICH. PMID:24970013

  6. Comparison of Physicochemical Characteristics and Anticoagulant Activities of Polysaccharides from Three Sea Cucumbers

    PubMed Central

    Luo, Lan; Wu, Mingyi; Xu, Li; Lian, Wu; Xiang, Jingying; Lu, Feng; Gao, Na; Xiao, Chuang; Wang, Shengmin; Zhao, Jinhua

    2013-01-01

    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. PMID:23385300

  7. Specific sulfation and glycosylation—a structural combination for the anticoagulation of marine carbohydrates

    PubMed Central

    Pomin, Vitor H.; Mourão, Paulo A. S.

    2014-01-01

    Based on considered achievements of the last 25 years, specific combinations of sulfation patterns and glycosylation types have been proved to be key structural players for the anticoagulant activity of certain marine glycans. These conclusions were obtained from comparative and systematic analyses on the structure-anticoagulation relationships of chemically well-defined sulfated polysaccharides of marine invertebrates and red algae. These sulfated polysaccharides are known as sulfated fucans (SFs), sulfated galactans (SGs) and glycosaminoglycans (GAGs). The structural combinations necessary for the anticoagulant activities are the 2-sulfation in α-L-SGs, the 2,4-di-sulfation in α-L-fucopyranosyl units found as composing units of certain sea-urchin and sea-cucumber linear SFs, or as branching units of the fucosylated chondroitin sulfate, a unique GAG from sea-cucumbers. Another unique GAG type from marine organisms is the dermatan sulfate isolated from ascidians. The high levels of 4-sulfation at the galactosamine units combined with certain levels of 2-sulfation at the iduronic acid units is the anticoagulant structural requirements of these GAGs. When the backbones of red algal SGs are homogeneous, the anticoagulation is proportionally dependent of their sulfation content. Finally, 4-sulfation was observed to be the structural motif required to enhance the inhibition of thrombin via heparin cofactor-II by invertebrate SFs. PMID:24639954

  8. Specific sulfation and glycosylation-a structural combination for the anticoagulation of marine carbohydrates.

    PubMed

    Pomin, Vitor H; Mourão, Paulo A S

    2014-01-01

    Based on considered achievements of the last 25 years, specific combinations of sulfation patterns and glycosylation types have been proved to be key structural players for the anticoagulant activity of certain marine glycans. These conclusions were obtained from comparative and systematic analyses on the structure-anticoagulation relationships of chemically well-defined sulfated polysaccharides of marine invertebrates and red algae. These sulfated polysaccharides are known as sulfated fucans (SFs), sulfated galactans (SGs) and glycosaminoglycans (GAGs). The structural combinations necessary for the anticoagulant activities are the 2-sulfation in α-L-SGs, the 2,4-di-sulfation in α-L-fucopyranosyl units found as composing units of certain sea-urchin and sea-cucumber linear SFs, or as branching units of the fucosylated chondroitin sulfate, a unique GAG from sea-cucumbers. Another unique GAG type from marine organisms is the dermatan sulfate isolated from ascidians. The high levels of 4-sulfation at the galactosamine units combined with certain levels of 2-sulfation at the iduronic acid units is the anticoagulant structural requirements of these GAGs. When the backbones of red algal SGs are homogeneous, the anticoagulation is proportionally dependent of their sulfation content. Finally, 4-sulfation was observed to be the structural motif required to enhance the inhibition of thrombin via heparin cofactor-II by invertebrate SFs.

  9. Comparison of physicochemical characteristics and anticoagulant activities of polysaccharides from three sea cucumbers.

    PubMed

    Luo, Lan; Wu, Mingyi; Xu, Li; Lian, Wu; Xiang, Jingying; Lu, Feng; Gao, Na; Xiao, Chuang; Wang, Shengmin; Zhao, Jinhua

    2013-02-01

    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.

  10. [The latest recommendations on the use of new oral anticoagulants in routine practice].

    PubMed

    Witkowski, Michał; Witkowska, Magdalena; Smolewski, Piotr

    2016-01-01

    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. PMID:26864063

  11. The use of hirudin as universal anticoagulant in haematology, clinical chemistry and blood grouping.

    PubMed

    Menssen, H D; Melber, K; Brandt, N; Thiel, E

    2001-12-01

    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

  12. A Systematic Review of the Benefits and Risks of Anticoagulation Following Traumatic Brain Injury

    PubMed Central

    Shen, Xian; Dutcher, Sarah K.; Palmer, Jacqueline; Liu, Xinggang; Kiptanui, Zippora; Khokhar, Bilal; Al-Jawadi, Mohammad H.; Zhu, Yue; Zuckerman, Ilene H.

    2014-01-01

    Objective The objective of the study was Tto synthesize the existing literature on benefits and risks of anticoagulant use after traumatic brain injury (TBI). Design: Systematic review A literature search was performed in Medline, IPA, Health Star and CINAHL on October 11, 2012 and updated on September 2, 2013, using terms related to TBI and anticoagulants. Main Measures Human studies evaluating the effects of post-TBI anticoagulation on venous thromboembolism (VTE), hemorrhage, mortality or coagulation parameters with original analyses were eligible for the review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed throughout the conduct of the review. Results Thirty-nine eligible studies were identified from the literature, of which 23 studies with complete information on post-TBI anticoagulant use and patient outcomes were summarized in this review. Meta-analysis was unwarranted due to varying methodological design and quality of the studies. Twenty-one studies focused on the effects of pharmacological thromboprophylaxis (PTP) post-TBI on VTE and/or progression of intracranial hemorrhage (ICH) while two RCTs analyzed coagulation parameters as the result of anticoagulation. Conclusion PTP appears to be safe among TBI patients with stabilized hemorrhagic patterns. More evidence is needed regarding effectiveness of PTP in preventing VTE as well as preferred agent, dose and timing for PTP. PMID:24992639

  13. [An outpatient clinic measure and control system for anticoagulation levels, CoaguChek XS].

    PubMed

    Romero Guardeño, Araceli; Pérez Lucena, Dolores Amalia

    2009-03-01

    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.

  14. Rodent resistance to the anticoagulant rodenticides, with particular reference to Denmark

    PubMed Central

    Lund, M.

    1972-01-01

    Inherited resistance to anticoagulant rodenticides was discovered in populations of Rattus norvegicus about 14 years ago. Similar resistance has now been reported from several countries in north-western Europe and from the USA. In order to detect resistance and to control it effectively, basic data on the susceptibility of rat populations are required for each country, and trapping surveys should be made in any area where resistance is suspected. Acute poisons are needed to control resistant rats although the shift from anticoagulants to acute poisons is a retrograde step as far as efficiency is concerned, and increases the hazard of control operations to man and other animals. Resistance to anticoagulants in Mus musculus has been reported from England, and resistant mice are probably to be found in other countries also in view of the great individual variation in susceptibility of this species to these rodenticides. PMID:4540680

  15. Clinical experience with novel oral anticoagulants for thromboprophylaxis after elective hip and knee arthroplasty.

    PubMed

    Messerschmidt, Cory; Friedman, Richard J

    2015-04-01

    Anticoagulant medications help to reduce the risk of thromboembolic events after total hip arthroplasty and total knee arthroplasty. Traditionally, this has been accomplished with medications, such as low-molecular-weight heparin and warfarin. However, these traditional anticoagulants possess a variety of shortcomings that leave much room for improvement. A new class of oral anticoagulants is now available, and present a more convenient option for safe and efficacious thromboprophylaxis in post arthroplasty patients, particularly in the outpatient setting. This review focuses on the direct thrombin inhibitor, dabigatran, and the selective factor Xa inhibitors, rivaroxaban and apixaban, and the clinical data to date about their use in total hip arthroplasty and total knee arthroplasty patients. PMID:25767271

  16. The susceptibility of Tatera indica, Nesokia indica and Bandicota bengalensis to three anticoagulant rodenticides.

    PubMed

    Greaves, J H; Rehman, A B

    1977-02-01

    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

  17. The susceptibility of Tatera indica, Nesokia indica and Bandicota bengalensis to three anticoagulant rodenticides.

    PubMed Central

    Greaves, J. H.; Rehman, A. B.

    1977-01-01

    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

  18. Structure and anticoagulant activity of fucosylated glycosaminoglycan degraded by deaminative cleavage.

    PubMed

    Zhao, Longyan; Lai, Sensen; Huang, Rong; Wu, Mingyi; Gao, Na; Xu, Li; Qin, Hongbo; Peng, Wenlie; Zhao, Jinhua

    2013-11-01

    Fucosylated glycosaminoglycans (FGs) are complex glycosaminoglycans that exhibit potent anticoagulant activity. To study the relationship between molecular size and biological activity, oligosaccharides with (2,5)-anhydro-D-talose units at new reducing ends were prepared by hydrazine deacetylation and nitrous acid depolymerization. The product chemical structures were analyzed by one- and two-dimensional NMR methods. Additionally, anticoagulant activities were evaluated by clotting assay and chromogenic substrate cleavage. The results demonstrated that under mild deacetylation and deaminative cleavage conditions, both products were relatively homogeneous and sulfated fucose branch types and sulfate substituents remained stable. These depolymerized FGs with different molecular sizes had potent intrinsic anticoagulant activities, which were similar to those that were obtained by free-radical depolymerization with similar molecular weights. Decreasing molecular weight may weaken activity but not significantly affect factor Xase and heparin cofactor II (HCII)-mediated thrombin inhibition.

  19. Anticoagulation in adults with congenital heart disease: The who, the when and the how?

    PubMed

    Jensen, A S; Idorn, L; Nørager, B; Vejlstrup, N; Sondergaard, L

    2015-03-01

    Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events. It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts. 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 recommendations for which patients are likely to benefit from which anticoagulation treatments, when they should be considered and how these would be carried out.

  20. [Perioperative management of direct oral anticoagulant in emergency surgery and bleeding. Haemostasis monitoring and treatment].

    PubMed

    Hidalgo, F; Gómez-Luque, A; Ferrandis, R; Llau, J V; de Andrés, J; Gomar, C; Sierra, P; Castillo, J; Torres, L M

    2015-10-01

    There is an almost unanimous consensus on the management of the direct new oral anticoagulants, dabigatran, rivaroxaban, and apixaban in elective surgery. However, this general consensus does not exist in relation with the direct new oral anticoagulants use in emergency surgery, especially in the bleeding patient. For this reason, a literature review was performed using the MEDLINE-PubMed. An analysis was made of the journal articles, reviews, systematic reviews, and practices guidelines published between 2000 and 2014 using the terms "monitoring" and "reversal". From this review, it was shown that the routine tests of blood coagulation, such as the prothrombin time and activated partial thromboplastin time, have a limited efficacy in the perioperative control of blood coagulation in these patients. There is currently no antidote to reverse the effects of these drugs, although the possibility of using concentrated prothrombin complex and recombinant activated factor vii has been suggested for the urgent reversal of the anticoagulant effect.

  1. Real Data on Effectiveness, Tolerability and Safety of New Oral Anticoagulant Agents: Focus on Dabigatran.

    PubMed

    Stabile, Eugenio; Izzo, Raffaele; Rozza, Francesco; Losi, Maria Angela; Coscioni, Enrico; Trimarco, Bruno

    2016-06-01

    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

  2. Trials of Novel Oral Anticoagulants for Stroke Prevention In Patients with Non-valvular Atrial Fibrillation

    PubMed Central

    Halperin, Jonathan L; Dorian, Paul

    2014-01-01

    Patients with non-valvular atrial fibrillation (AF) face an increased risk of stroke compared with those in normal sinus rhythm. The vitamin K antagonist warfarin, available for over half a century, is highly effective in reducing the risk of stroke in patients with AF, but it is a difficult drug to use properly. As a result, it is challenging to keep the anticoagulant effect of warfarin in the desired range. Newer oral anticoagulants (NOACs) that directly inhibit Factor IIa (thrombin) or Factor Xa provide reliable anticoagulation when administer in fixed oral doses without routine coagulation monitoring. This manuscript will review in detail the pivotal trials of these NOACs that led to their approval as well as comment on the factors that should influence their selection. PMID:24821657

  3. The predictability of bleeding by prothrombin times sensitive or insensitive to PIVKA during intensive oral anticoagulation.

    PubMed

    Arnesen, H; Smith, P

    1991-02-01

    To evaluate the effect of PIVKA (Proteins Induced by Vitamin K Absence or Antagonism) on the bleeding tendency during oral anticoagulation, we studied consecutive patients intensively treated with warfarin (INR greater than 4.8). The level of anticoagulation was measured with the PIVKA-insensitive Normotest (NT) as well as with the PIVKA-sensitive Thrombotest (TT), and the results are expressed as per cent coagulant activity. The NT/TT ratio was determined. Twenty patients with bleeding episodes had a mean NT/TT ratio of 2.06 as compared to 2.20 in 143 patients without bleeding episodes (p = 0.08). As the NT/TT ratio was not higher in patients with bleedings, we conclude that PIVKA are of no importance for bleeding during anticoagulation with vitamin K antagonists.

  4. Coagulation activation after discontinuation of VTE treatment with different oral anticoagulants and impact on 12-month clinical outcomes.

    PubMed

    Beyer-Westendorf, Jan; Gehrisch, Siegmund; Stange, Thoralf; Tittl, Luise; Siegert, Gabriele; Weiss, Norbert

    2015-08-01

    Increasing D-dimer (DD) levels after discontinuation of vitamin K antagonist (VKA) therapy indicate an increased risk of recurrence of venous thromboembolism (VTE). However, after discontinuation of direct-acting non-VKA oral anticoagulants (DOACs or NOACs) the extent of coagulation activation and its clinical impact is unknown. Blood samples were collected from consenting patients with proximal VTE at the end of anticoagulation treatment with apixaban (n=37), dabigatran (n=17), rivaroxaban (n=9) or VKA (n=184) and 4weeks later. DD, prothrombin fragments F1+2 (F1+2) and thrombin-antithrombin complexes (TAT) were measured. All patients underwent follow-up at 12months to establish recurrent VTE or death from any cause. Irrespective of the treatment, DD and F1+2 but not TAT demonstrated a similar increase between baseline and week 4. At 12months, 18 patients (7.3%) had recurrent VTE and two (0.8%) had died. For all patients and subgroups of VKA and DOAC, positive likelihood ratios were numerically higher for baseline values but only TAT values at 4weeks were found to be related to a small increase of outcome event likelihood (2.6; 95%CI 1.23-5.50), which was driven by VKA patients (3.1; 95%CI 1.32-7.30) and not by DOAC patients (2.27; 95%CI 0.52-9.95). For all parameters, negative likelihood ratios were not predictive. In logistic regression analysis, only ΔTAT (optimal cut-off >178% from baseline demonstrated a significant risk increase for VTE/death (odds ratio 3.76; 95% confidence interval 1.46-9.68; p=0.006). In conclusion, the concept of testing coagulation activation parameters may also be transferred to VTE patients at the end of DOAC therapy. For patients with an increase of TAT levels within 4weeks after treatment discontinuation (>178% from baseline) is associated with an increased risk for VTE recurrence or death at 12months.

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

    PubMed Central

    Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

    2015-01-01

    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. PMID:26998384

  6. Specific antidotes in development for reversal of novel anticoagulants: a review.

    PubMed

    Gomez-Outes, Antonio; Suarez-Gea, M L; Lecumberri, Ramon; Terleira-Fernandez, Ana I; Vargas-Castrillon, Emilio

    2014-01-01

    In the last decade, several direct oral anticoagulants (DOAC; dabigatran, rivaroxaban, apixaban, edoxaban) have been marketed for prophylaxis and/or treatment of thromboembolism without having specific antidotes available for their reversal. Current management of bleeding associated to DOAC includes the removal of all antithrombotic medications and supportive care. Non-specific procoagulant agents (prothrombin complex concentrates and activated factor VIIa) have been used in case of serious bleeding. Currently, some specific antidotes for the DOAC are under development. Idarucizumab (BI 655075; Boehringer Ingelheim) is a fragment of an antibody (Fab), which is a specific antidote to the oral direct thrombin inhibitor dabigatran. Andexanet alfa (r-Antidote, PRT064445; Portola Pharmaceuticals) is a truncated form of enzymatically inactive factor Xa, which binds and reverses the anticoagulant action of the factor Xa inhibitors (e.g.: rivaroxaban, apixaban and edoxaban). Aripazine (PER-977, ciraparantag; Perosphere Inc.) is a synthetic small molecule (~500 Da) that reverses oral dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH in vivo. These antidotes could provide an alternative for management of life-threatening bleeding events occurring with the above-mentioned anticoagulants. In addition, the specific antidote anivamersen (RB007; Regado Biosciences Inc.) is an RNA aptamer in clinical development to reverse the anticoagulant effect of the parenteral factor IXa inhibitor pegnivacogin, which is also in development. This anticoagulant-antidote pair may provide an alternative in situations in which a fast onset and offset of anticoagulation is needed, like in patients undergoing cardiac surgery with extracorporeal circulation, as an alternative to the heparin/protamine pair. This patent review includes a description of the pharmacological characteristics of the novel specific antidotes, the available results from completed non

  7. Detection and quantification of lupus anticoagulants in plasma from heparin treated patients, using addition of polybrene

    PubMed Central

    Jacobsen, Eva M; Trettenes, Elin J; Wisløff, Finn; Abildgaard, Ulrich

    2006-01-01

    Background Lupus anticoagulants prolong clotting times in phospholipid-dependent coagulation tests. Lupus Ratio assays are integrated tests for lupus anticoagulants that may be based on APTT, RVVT or dPT clotting times. If a patient is being treated with unfractionated heparin, however, the heparin prolong clotting times and the diagnosis of lupus anticoagulant is invalidated. Commercial assays may have heparin neutralising agents added to their reagents. However, the type and efficacy of the heparin neutralisation is often not documented. We wanted to test the influence and efficacy of heparin neutralisers in the Lupus Ratio assay. Methods Several heparin neutralisers were tested, and polybrene was chosen for further testing. Unfractionated heparin and/or polybrene were added to normal plasma and to plasma from patients with or without lupus anticoagulant and clotting times compared before and after the additions. Lupus anticoagulant-positive patients were given 5000 IU i.v. of unfractionated heparin and plasma was collected just before and five minutes after the injection. Lupus Ratios were calculated after polybrene was added to the postinjection samples. Results The Lupus Ratio became slightly lower when polybrene was added to plasma without heparin. Plasma heparinised in vitro and plasma from patients that had received heparin, both had Lupus Ratios nearly identical to the Lupus Ratios calculated before any additions. Conclusion By addition of polybrene to a final concentration of 7.9 μg/ml in test plasma, Lupus Ratio may be determined in lupus anticoagulant-negative as well as positive plasmas irrespective of the presence of heparin 0.0 – 1.3 U/ml. PMID:16436199

  8. Effect of anticoagulation on cardioembolic stroke severity, outcomes and response to intravenous thrombolysis.

    PubMed

    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

    2016-07-01

    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 <1.5, (2) anticoagulated with INR 1.5-1.9 and (3) anticoagulated with INR ≥2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (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 <1.5 group, 13.3 % to the INR 1.5-1.9 and 10.5 % 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 <10) (OR 2.026, 95 % CI 1.006-4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173-3.789) as well as INR 1.5-1.9 (OR 3.676, 95 % CI 1.510-8.946) were associated with favorable outcomes (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

  9. Effect of magnetic bracelets on the coagulation and anticoagulation systems of the blood of patients with hypertension

    NASA Technical Reports Server (NTRS)

    Bublis, V. V.; Zabrodina, L. V.; Platonova, A. T.; Meyerova, Y. A.

    1974-01-01

    The data which have been obtained on the influence of magnetic bracelets on the coagulation and anticoagulation systems of the blood indicate that the wearing of magnetic bracelets results in a decrease in the coagulation activity of the blood and an increase in the activity of the anticoagulation system. These changes must be viewed as favorable for patients with cardiovascular pathology.

  10. The response of the Egyptian spiny mouse (Acomys cahirinus) and two other species of commensal rodents to anticoagulant rodenticides.

    PubMed

    Mahmoud, W; Redfern, R

    1981-06-01

    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

  11. The response of the Egyptian spiny mouse (Acomys cahirinus) and two other species of commensal rodents to anticoagulant rodenticides

    PubMed Central

    Mahmoud, Wafeya; Redfern, R.

    1981-01-01

    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

  12. Implementation of non-vitamin K antagonist oral anticoagulants in daily practice: the need for comprehensive education for professionals and patients.

    PubMed

    Heidbuchel, Hein; Berti, Dana; Campos, Manuel; Desteghe, Lien; Freixo, Ana Parente; Nunes, António Robalo; Roldán, Vanessa; Toschi, Vincenzo; Lassila, Riitta

    2015-01-01

    Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for the prevention and treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. NOACs do not require routine coagulation monitoring, creating a challenge to established systems for patient follow-up based on regular blood tests. Healthcare professionals (HCPs) are required to cope with a mixture of patients receiving either a vitamin K antagonist or a NOAC for the same indications, and both professionals and patients require education about the newer drugs. A European working group convened to consider the challenges facing HCPs and healthcare systems in different countries and the educational gaps that hinder optimal patient management. Group members emphasised the need for regular follow-up and noted national, regional and local variations in set-up and resources for follow-up. Practical incorporation of NOACs into healthcare systems must adapt to these differences, and practical follow-up that works in some systems may not be able to be implemented in others. The initial prescriber of a NOAC should preferably be a true anticoagulation specialist, who can provide initial patient education and coordinate the follow-up. The long-term follow-up care of patients can be managed through specialist coagulation nurses, in a dedicated anticoagulation clinic or by general practitioners trained in NOAC use. The initial prescriber should be involved in educating those who perform the follow-up. Specialist nurses require access to tools, potentially including specific software, to guide systematic patient assessment and workflow. Problem cases should be referred for specialist advice, whereas in cases for which minimal specialist attention is required, the general practitioner could take responsibility for patient follow-up. Hospital departments and anticoagulation clinics should proactively engage with all downstream HCPs (including pharmacists) to ensure

  13. [Treatment of very old patients with non valvular atrial fibrillation. The valuable opportunity offered by new oral anticoagulants, to be cautiously used].

    PubMed

    Orso, Francesco; Barucci, Riccardo; Fracchia, Stefania; Mannarino, Giulio; Pratesi, Alessandra; Fattirolli, Francesco

    2013-12-01

    Atrial Fibrillation (AF) is the most frequent cardiac arrhythmia and its incidence increases with age reaching a 10% prevalence in the oldest old. Patients with AF have a five-fold increase in the risk of stroke. Current guidelines on AF management recommend the prescription of oral anticoagulant therapy in patients at medium and high risk of thromboembolic events. Advanced age is a risk factor for stroke in AF, but despite clear evidences a high rate of OAT under prescription is reported and particularly in the oldest old. Among the main causes of this phenomenon an enhanced risk of bleeding is often reported: this due to several factors: risk of falls, the presence of comorbidity and polifarmacy and a reduction in compliance and adherence that are common in the elderly. In recent years the international scenario in the management of OAT has significantly changed since the introduction of the new oral anticoagulants (NOA): Dabigatran, a direct thrombin inhibitor, and two oral factor Xa inhibitors Rivaroxaban and Apixaban, which have all been tested in randomized clinical trial (RELY, ROCKET-AF e ARISTOTLE) which have demonstrated non inferiority compared to warfarin in the prevention of thromboembolic events with an optimal safety profile. NOA could be an important therapeutic opportunity for stroke prevention in elderly patients with AF even if the substantial differences in mean age, anthropometric measures and comorbidity of the patients enrolled in these trials compared with those of the real world setting, oblige some caution and discussion.

  14. A comparative proteomic analysis of HepG2 cells incubated by S(-) and R(+) enantiomers of anti-coagulating drug warfarin.

    PubMed

    Bai, Jing; Sadrolodabaee, Laleh; Ching, Chi Bun; Chowbay, Balram; Ning Chen, Wei

    2010-04-01

    Warfarin is a commonly prescribed oral anti-coagulant with narrow therapeutic index. It interferes with vitamin K cycle to achieve anti-coagulating effects. Warfarin has two enantiomers, S(-) and R(+) and undergoes stereoselective metabolism, with the S(-) enantiomer being more effective. We reported that the intracellular protein profile in HepG2 cells incubated with S(-) and R(+) warfarin, using iTRAQ-coupled 2-D LC-MS/MS. In samples incubated with S(-) and R(+) warfarin alone, the multi-task protein Protein SET showed significant elevation in cells incubated with S(-) warfarin but not in those incubated with R(+) warfarin. In cells incubated with individual enantiomers of warfarin in the presence of vitamin K, protein disulfide isomerase A3 which is known as a glucose-regulated protein, in cells incubated with S(-) warfarin was found to be down-regulated compared to those incubated with R(+) warfarin. I