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Antidote for dabigatran

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https://www.readbyqxmd.com/read/27920714/idarucizumab-as-antidote-to-intracerebral-hemorrhage-under-treatment-with-dabigatran
#1
Valentin Held, Philipp Eisele, Christoph C Eschenfelder, Kristina Szabo
BACKGROUND AND PURPOSE: Non-vitamin K anticoagulants (NOAC) such as dabigatran have become important therapeutic options for the prevention of stroke. Until recently, there were only nonspecific agents to reverse their anticoagulant effects in a case of emergency. Idarucizumab, an antibody fragment targeting dabigatran, is the first specific antidote for a NOAC to be approved, but real-world experience is limited. METHODS: We report two cases of patients on dabigatran with acute intracerebral hemorrhage who received idarucizumab...
September 2016: Case Reports in Neurology
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#2
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911120/new-frontiers-in-anticoagulation-non-vitamin-k-oral-anticoagulants-in-stroke-prevention
#3
Valentina Arnao, Marianna Riolo, Antonino Tuttolomondo, Antonio Pinto, Brigida Fierro, Paolo Aridon
Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert Commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists...
December 2, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27900867/-new-direct-oral-anticoagulants-actual-review
#4
Jana Michalcová, Miroslav Penka, Alena Buliková, Jiřina Zavřelová, Andrea Štěpařová
In recent years the options of anticoagulant/antithrombotic therapy have extended with new - direct oral anticoagulants, comprising direct thrombin inhibitors (dabigatran etexilate) and direct factor Xa inhibitors (rivaroxaban, apixaban). These agents represent another progress towards "the ideal antithrombotic drug", and thus towards a safe and effective antithrombotic therapy. The following article provides actual review and recommendations for clinical practice, including laboratory assessment and management of emergency situations...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27789605/reversal-of-anticoagulation-and-management-of-bleeding-in-patients-on-anticoagulants
#5
Prajwal Dhakal, Supratik Rayamajhi, Vivek Verma, Krishna Gundabolu, Vijaya R Bhatt
Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4...
October 26, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27766043/doacs-advances-and-limitations-in-real-world
#6
Lai Heng Lee
The group of new oral anticoagulants or NOACs, now termed direct oral anticoagulants or DOACs, with their favourable results from large scale phase III clinical trials, represent a major advancement and expanded armamentarium in antithrombotic therapy. Dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Usage of the DOACs is expected to increase as clinicians gain more experience and reassurance with data from the real world studies which are generally consistent with that from clinical trials...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27752290/reversal-of-direct-oral-anticoagulants-in-hemophilia-treatment-ash-meeting-2015
#7
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
https://www.readbyqxmd.com/read/27697119/-reversal-strategies-for-non-vitamin-k-antagonist-oral-anticoagulants
#8
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
https://www.readbyqxmd.com/read/27669031/reversal-of-anticoagulation-with-dabigatran-in-an-82-year-old-patient-with-traumatic-retroperitoneal-arterial-bleeding-using-the-new-antidote-idarucizumab-a-case-report
#9
Stefan Hofer, Christoph Philipsenburg, Markus A Weigand, Thorsten Brenner
Dabigatran etexilate is a direct oral anticoagulant used for the prevention of stroke in atrial fibrillation. Idarucizumab is a recently approved specific antidote that reverses the effect of dabigatran within minutes. We report the case of an 82-year-old patient with traumatic retroperitoneal arterial bleeding under anticoagulation with dabigatran etexilate. By administration of idarucizumab, we successfully normalized coagulation and saved the patient from an operation. In the course of the disease, a slight reincrease in dabigatran etexilate plasma levels was observed 2 days after the reversal, which could lead to a new onset of bleeding...
December 1, 2016: A & A Case Reports
https://www.readbyqxmd.com/read/27658470/direct-oral-anticoagulants-in-emergency-trauma-admissions
#10
Marc Maegele, Oliver Grottke, Herbert Schöchl, Oliver A Sakowitz, Michael Spannagl, Jürgen Koscielny
BACKGROUND: Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery...
September 5, 2016: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/27626268/-antidotes-to-novel-direct-oral-anticoagulants
#11
N G Khorev, A P Momot, V O Kon'kova
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)...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/27594818/novel-oral-anticoagulants-for-venous-thromboembolism-with-special-emphasis-on-risk-of-hemorrhagic-complications-and-reversal-agents
#12
Zaheer Ahmed, Seemeen Hassan, Gary A Salzman
Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes...
April 2016: Current Drug Therapy
https://www.readbyqxmd.com/read/27548686/reversal-agents-for-direct-oral-anticoagulants-understanding-new-and-upcoming-options
#13
Kelly C Rogers, Melanie P Shelton, Shannon W Finks
Direct oral anticoagulants (DOACs), originally developed as an alternative for vitamin K antagonists, are shifting the landscape of antithrombotic therapy. DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban offer enhancements in safety, convenience, and efficacy compared with warfarin. However, as choices for oral anticoagulation therapy have increased, so has the need for effectual antidotes before urgent surgical procedures and for the reversal of serious adverse events caused by DOACs. To date, one antidote has been FDA approved in the United States for the reversal of dabigatran, and two antidotes are undergoing phase 2and 3clinical trials...
November 2016: Cardiology in Review
https://www.readbyqxmd.com/read/27545637/-new-oral-anticoagulants-noac-in-nephrology
#14
Antonio Bellasi, Luca Di Lullo, Gianvincenzo Melfa, Claudio Minoretti, Carlo Ratti, Carlo Campana, Maurizio Volpi, Stefano Mangano, Biagio Di Iorio, Mario Cozzolino
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...
July 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/27543264/management-of-bleeding-in-patients-treated-with-direct-oral-anticoagulants
#15
REVIEW
Marcel Levi
BACKGROUND: Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on encouraging results for efficacy and safety in clinical studies. An initial limitation of these new drugs was the absence of an adequate strategy to reverse the effect if a bleeding event occurs or an urgent invasive procedure has to be carried out. MAIN TEXT: Specific reversing agents for DOACs have become available, however, and are now evaluated in clinical studies...
August 20, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27455511/a-rapid-pro-hemostatic-approach-to-overcome-direct-oral-anticoagulants
#16
Nabil K Thalji, Lacramioara Ivanciu, Robert Davidson, Phyllis A Gimotty, Sriram Krishnaswamy, Rodney M Camire
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...
August 2016: Nature Medicine
https://www.readbyqxmd.com/read/27380051/-perioperative-coagulation-management-during-ascending-aorta-replacement-on-apixaban
#17
C Dumps, E Halbeck, J Schimpf, H Forst
The direct oral anticoagulants (DOACs) present a valid therapeutic alternative to vitamin K antagonists in patients with non-valvular atrial fibrillation, for the prevention of venous thromboembolism, and for the treatment and prevention of the recurrence of pulmonary embolisms and deep vein thrombosis. Despite Idarucizumab as an antagonist of Dabigatran there are no other specific antidotes available yet. Therefore, perioperative coagulation management by DOACs is challenging in patients undergoing emergency surgical procedures with a high risk of bleeding complications...
August 2016: Der Anaesthesist
https://www.readbyqxmd.com/read/27297852/noac-monitoring-reversal-agents-and-post-approval-safety-and-effectiveness-evaluation-a-cardiac-safety-research-consortium-think-tank
#18
REVIEW
James A Reiffel, Jeffrey I Weitz, Paul Reilly, Edvardas Kaminskas, Troy Sarich, Philip Sager, Jonathan Seltzer
Four non-vitamin K antagonist oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) have been approved in the United States for treatment of atrial fibrillation (AF) and venous thromboembolic disease. They have been as or more effective than the prior standards of care, with less fatal or intracranial bleeding, fewer drug and dietary interactions, and greater patient convenience. Nonetheless, the absence of the ability for clinicians to assess compliance or washout with a simple laboratory test (or to adjust dosing with a similar assessment) and the absence of an antidote to rapidly stop major hemorrhage or to enhance safety in the setting of emergent or urgent surgery/procedures have been limitations to greater non-vitamin K antagonist oral anticoagulant usage and better thromboembolic prevention...
July 2016: American Heart Journal
https://www.readbyqxmd.com/read/27297642/-direct-oral-anticoagulant-associated-bleeding
#19
A Godier, A-C Martin, N Rosencher, S Susen
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...
July 2016: Journal des Maladies Vasculaires
https://www.readbyqxmd.com/read/27293895/direct-acting-oral-anticoagulants-practical-considerations-for-emergency-medicine-physicians
#20
REVIEW
W Frank Peacock, Zubaid Rafique, Adam J Singer
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...
2016: Emergency Medicine International
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