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Anticoagulant reversal

Qiang Tan, Qianwei Chen, Zhou Feng, Xia Shi, Jun Tang, Yihao Tao, Bing Jiang, Liang Tan, Hua Feng, Gang Zhu, Yunfeng Yang, Zhi Chen
Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats...
October 18, 2016: Brain Research
Yuhang Zhou, Shaji Abraham, Stephanie Renna, Leonard C Edelstein, Carol A Dangelmaier, Alexander Y Tsygankov, Satya P Kunapuli, Paul F Bray, Steven E McKenzie
OBJECTIVE: The objective of this study is to investigate the role of T-cell ubiquitin ligand-2 (TULA-2) in the platelet Fc receptor for IgG IIA (FcγRIIA) pathway and in the pathogenesis of heparin-induced thrombocytopenia (HIT). APPROACH AND RESULTS: HIT is a life-threatening thrombotic disease in which IgG antibodies against the heparin-platelet factor 4 complex activate platelets via FcγRIIA. We reported previously differential expression of TULA-2 in human population was linked to FcγRIIA responsiveness...
October 20, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
Clemens Feistritzer, Stefan Schmidt
During the 57(th) annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted...
2016: Memo
Katherine J Hahn, Shannon J Morales, James H Lewis
Anticoagulants are a well known cause of drug-induced liver injury (DILI). We recently encountered a 45-year-old male who developed DILI during treatment with enoxaparin, a low-molecular-weight heparin (LMWH), for dural venous thrombosis. The man received enoxaparin 80 mg subcutaneously, twice daily. After 4 days, the patient was asymptomatic but he developed liver aminotransferase elevations: AST 340 U/L and ALT 579 U/L. Investigation revealed an R ratio of 19.9 by day 5 and a Roussel Uclaf Causality Assessment Method score of 10, giving a high probable likelihood that enoxaparin was the cause of hepatic injury...
December 2015: Drug Saf Case Rep
Aung Myat, Udaya S Tantry, Jacek Kubica, Paul A Gurbel
Introduction A P2Y12 inhibitor plus aspirin is the most widely used antiplatelet strategy to prevent adverse outcomes in the setting of atherothrombotic vascular disease. Areas Covered A paucity of robust evidence for an optimal dose, gastrointestinal toxicity, ineffectiveness in high-risk patients and interactions with other antiplatelet agents, are major controversies associated with aspirin therapy. Ticagrelor is a reversibly binding oral P2Y12 receptor blocker that mediates potent inhibition of adenosine diphosphate-induced platelet function...
October 14, 2016: Expert Review of Cardiovascular Therapy
Nasim Shahidi Hamedani, Heiko Rühl, Julia Janina Zimmermann, Tim Heiseler, Johannes Oldenburg, Günter Mayer, Bernd Pötzsch, Jens Müller
Activated protein C (APC) is a critical regulator of thrombin formation and thereby protects against thrombosis. On the other hand, overwhelming formation of APC increases the risk of bleeding such as in trauma-induced coagulopathy. Thus, pharmacological inhibition of APC activity may improve blood clottability in certain clinical situations. In this study, we demonstrate that the DNA aptamer HS02-52G binds with fast onset (1.118 ± 0.013 × 10(5) M(-1) s(-1)) to APC and possesses a long residence time of 13...
October 13, 2016: Nucleic Acid Therapeutics
Luke Miller, Jason A Ferreira, Calvin Tucker
BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding...
October 8, 2016: Journal of Emergency Medicine
Fatima Urooj, Abhishek Kulkarni, Dwight Stapleton, Edo Kaluski
The choice of an oral anticoagulant (OAC) for patients with nonvalvular atrial fibrillation (NVAF) is a major and complex clinical decision taking into account the individual risk-benefit ratio and bearing in mind the chronicity of therapy. This review focuses on the safety and efficacy of new oral anticoagulants (NOACs) compared with conventional vitamin K antagonists (VKA) in patients with NVAF. Current data suggest that NOACs are at least as effective and safe as VKAs for most NVAF subjects. The NOACs do not mandate dietary restrictions and regular pharmacodynamic monitoring, and they seem to have lesser incidence of intracranial or fatal bleeding when compared with VKAs...
October 7, 2016: Clinical Cardiology
N Appleby, E Groarke, M Crowley, F A Wahab, A M McCann, L Egan, D Gough, G McMahon, D O'Donghaile, D O'Keeffe, N O'Connell
BACKGROUND: Real-world studies of the emergency reversal of warfarin using 4-factor prothrombin complex concentrate (PCC) report unwarranted delays. The delay to receiving PCC was ≥ 8 h in 46·7% of patients with warfarin-associated bleeding (PWAB) treated with a variable PCC dosing protocol in our retrospective audit. OBJECTIVE: To report the impact of a simplified PCC dosing protocol on the interval to reversal of anticoagulation. METHODS: We developed a PCC dosing protocol standardising the initial PCC dose and simplifying dosing calculations...
October 7, 2016: Transfusion Medicine
Paul A Reilly, Joanne van Ryn, Oliver Grottke, Stephan Glund, Joachim Stangier
The direct oral anticoagulants (DOACs) provide a number of clinical advantages over vitamin K antagonists for the treatment of thromboembolism, including improved efficacy and safety, as well as no need for regular monitoring of anticoagulant effect. However, as with all anticoagulants, bleeding complications may occur, and anticoagulant reversal may be required in specific clinical situations, such as in patients experiencing spontaneous or traumatic bleeds, or in anticoagulated patients requiring emergency surgery or other invasive procedures...
September 28, 2016: American Journal of Emergency Medicine
Truman J Milling, Scott Kaatz
Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development...
September 28, 2016: American Journal of Emergency Medicine
Jerrold H Levy
Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures...
September 29, 2016: American Journal of Emergency Medicine
John Eikelboom, Geno Merli
The risk of bleeding in the setting of anticoagulant therapy continues to be re-evaluated following the introduction of a new generation of direct oral anticoagulants (DOACs). Interruption of DOAC therapy and supportive care may be sufficient for the management of patients who present with mild or moderate bleeding, but in those with life-threatening bleeding, a specific reversal agent is desirable. We review the phase 3 clinical studies of dabigatran, rivaroxaban, apixaban, and edoxaban in patients with nonvalvular atrial fibrillation, in the context of bleeding risk and management...
September 29, 2016: American Journal of Emergency Medicine
Menno V Huisman, John Fanikos
As expected with all antithrombotic agents, there is a risk of bleeding complications in patients receiving direct oral anticoagulants (DOACs) because of the DOAC itself, acute trauma, invasive procedures, or underlying comorbidities. For many bleeding events, a prudent course of action will be to withdraw the DOAC, then "wait and support" the patient, with the expectation that the bleeding event should resolve with time. Likewise, DOAC therapy may be interrupted ahead of a planned procedure, the stopping time being dependent on the agent involved and the patient's renal function...
September 28, 2016: American Journal of Emergency Medicine
Charles V Pollack
No abstract text is available yet for this article.
September 28, 2016: American Journal of Emergency Medicine
Charles V Pollack
Idarucizumab is a monoclonal antibody fragment specifically targeted to dabigatran. It has demonstrated prompt and durable reversal of the anticoagulant effects of dabigatran in animal studies and phase 1 studies of young, elderly, and renally impaired volunteers. Although elective invasive procedures and most bleeding complications in dabigatran-treated patients can be managed by temporarily stopping dabigatran therapy and using supportive measures, there are rare clinical situations that require urgent reversal of the anticoagulant effect of dabigatran...
September 28, 2016: American Journal of Emergency Medicine
Frederik Uttenthal Larsen, Anne-Mette Hvas, Erik Lerkevang Grove
Non-vitamin K oral anticoagulants (NOACs) are alternatives to vitamin K antagonists and provide consistent anticoagulation with equal or better clinical outcome and no need for routine monitoring. Bleeding is a feared complication of anticoagulants. Until recently, no specific agent has been available for reversal of NOACs. Idarucizumab binds dabigatran for rapid reversal of its activity without procoagulant effects. Andexanet alpha (expected release in 2016) and PER977 are antidotes under clinical development...
October 3, 2016: Ugeskrift for Laeger
Andrea Morotti, Joshua N Goldstein
Direct oral anticoagulants (DOAC) are an attractive therapeutic option for anticoagulant treatment in the setting of venous thromboembolism or non-valvular atrial fibrillation. These drugs overall appear to have a lower risk of life-threatening hemorrhage than the vitamin K antagonists. In addition, they demonstrate more predictable and stable pharmacokinetics. Measurement of the degree of anticoagulation is desirable in patients with DOAC-associated hemorrhage, but commonly available coagulation assays show poor sensitivity for degree of DOAC effect...
November 2016: Current Treatment Options in Neurology
Supreet Kaur, Abhishek Kumar, Robert G Lerner, Wilbert S Aronow
The newer non-vitamin K dependent anticoagulants (NOACs) have provided a new tool in the armamentarium of physicians treating nonvalvular atrial fibrillation and thromboembolism. Slowly, but steadily, there has been an increased preference of NOACs over vitamin K antagonists. However, the major limiting factor and the concern that precluded their use was lack of reversal in emergent situations. With the advent of reversal agents such as idarucizumab, andexanet alfa and PER977, this gap is also being filled...
October 1, 2016: Archives of Medical Science: AMS
H C Diener, R Bernstein, K Butcher, B Campbell, G Cloud, A Davalos, S Davis, J M Ferro, M Grond, D Krieger, G Ntaios, A Slowik, E Touzé
Systemic thrombolysis with rt-PA is contraindicated in patients with acute ischemic stroke anticoagulated with dabigatran. This expert opinion provides guidance on the use of the specific reversal agent idarucizumab followed by rt-PA and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran. The use of idarucizumab followed by rt-PA is covered by the label of both drugs.
September 30, 2016: International Journal of Stroke: Official Journal of the International Stroke Society
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