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Anticoagulation antidotes

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https://www.readbyqxmd.com/read/28673500/-state-of-the-art-direct-oral-anticoagulants-and-transfusion
#1
A-C Martin, A Godier, D M Smadja, L Mauge, A-M Fischer
Direct oral anticoagulants (DOAC) are indicated for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism. As any anticoagulant, they are associated with a bleeding risk. Management of DOAC-induced bleeding is challenging. Idarucizumab, antidote for dabigatran, is currently available and is part of the therapeutic strategy, whereas antidotes for anti-Xa agents are under development. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain...
June 30, 2017: Transfusion Clinique et Biologique: Journal de la Société Française de Transfusion Sanguine
https://www.readbyqxmd.com/read/28662704/thrombocytopenia-induced-by-dabigatran-two-case-reports
#2
Hyun Goo Kang, Seung Jae Lee, Ji Yeon Chung, Jin Sung Cheong
BACKGROUND: Vitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These agents have been mainstays of anticoagulation for people older than 60 years. However, their administration is associated with a risk of bleeding and requires careful monitoring of patients. Novel oral anticoagulants (NOACs), such as dabigatran, are significantly safer in preventing thromboembolism than warfarin and heparin (sporadically causes thrombocytopenia) and are more specific for their target protein, thrombin...
June 29, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28594360/rapid-complexation-of-aptamers-by-their-specific-antidotes
#3
Heidi Stoll, Heidrun Steinle, Nadja Wilhelm, Ludmilla Hann, Silju-John Kunnakattu, Miwako Narita, Christian Schlensak, Hans P Wendel, Meltem Avci-Adali
Nucleic acid ligands, aptamers, harbor the unique characteristics of small molecules and antibodies. The specificity and high affinity of aptamers enable their binding to different targets, such as small molecules, proteins, or cells. Chemical modifications of aptamers allow increased bioavailability. A further great benefit of aptamers is the antidote (AD)-mediated controllability of their effect. In this study, the AD-mediated complexation and neutralization of the thrombin binding aptamer NU172 and Toll-like receptor 9 (TLR9) binding R10-60 aptamer were determined...
June 8, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28585328/the-recommended-dose-of-idarucizumab-may-not-always-be-sufficient-for-sustained-reversal-of-dabigatran-comment
#4
LETTER
A Tripodi
No abstract text is available yet for this article.
June 6, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28581331/exploring-indications-for-the-use-of-direct-oral-anticoagulants-and-the-associated-risks-of-major-bleeding
#5
Truman J Milling, Jennifer Frontera
Thrombosis is a leading cause of morbidity and mortality in the United States. Arterial and venous thromboses are implicated in the pathogenesis of major disorders, including myocardial infarction, ischemic stroke, and venous thromboembolism. Over the past decade, direct oral anticoagulants (DOACs) (eg, direct thrombin inhibitor and factor Xa [FXa] inhibitors) have been adopted as alternatives to warfarin due to their clinical advantages and efficacy for the treatment of thrombosis. As with all anticoagulants, treatment with DOACs is associated with a risk of major bleeding, including life-threatening gastrointestinal bleeds and intracranial hemorrhages (ICHs)...
April 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28551921/-management-of-anticoagulant-and-antiplatelet-therapy-in-patients-undergoing-planned-endoscopic-procedures
#6
REVIEW
Orly Sneh Arbib, Yaron Niv, Dorit Blickstein
Antithrombotic and antiplatelet therapy is widely used for primary and secondary prevention of venous and arterial diseases. Hemorrhage is a frequent complication in patients taking these drugs, especially during and post invasive procedures. There are several oral anticoagulants and antiplatelet drugs that differ from each other in the mechanism of action and metabolism, the need for drug monitoring, antidote, and the peri-procedural management of the drug. The risk of bleeding in gastrointestinal endoscopic procedures can be high (≥ 1...
April 2017: Harefuah
https://www.readbyqxmd.com/read/28549534/dabigatran-reversal-in-a-patient-with-end-stage-liver-disease%C3%A2-and-acute-kidney-injury
#7
James E Novak, Khalid Alamiri, Jerry Yee
Dabigatran, a direct thrombin inhibitor and one of the new class of direct oral anticoagulants, is increasingly used in preference to warfarin because of its efficacy and ease of administration. However, because the drug is cleared by the kidneys, it can accumulate in plasma and increase the risk for bleeding in patients with decreased kidney function. We report a patient with end-stage liver disease who developed life-threatening hemorrhage and acute kidney injury while taking dabigatran, 150mg, twice daily...
May 24, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28546438/specific-antidotes-for-bleeding-associated-with-direct-oral-anticoagulants
#8
Allison Burnett, Deborah Siegal, Mark Crowther
No abstract text is available yet for this article.
May 25, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28536761/-anticoagulation-direct-oral-anticoagulants
#9
B Kemkes-Matthes
Since direct oral anticoagulants (DOAC) have become available, use of anticoagulant treatment has become easier and safer-for patients suffering from thromboembolic diseases as well as for patients with atrial fibrillation: Because of constant bioavailability, fixed dose regimen treatment is possible, monitoring not necessary and severe bleeding complications-particularly intracranial hemorrhages-rare in comparison to vitamin K anticoagulants. To gain all these advantages, it is essential to give DOAC in the correct dosage...
June 2017: Der Internist
https://www.readbyqxmd.com/read/28524847/an-in-vivo-strategy-to-counteract-post-administration-anticoagulant-activity-of-azido-warfarin
#10
Sylvain Ursuegui, Marion Recher, Wojciech Krężel, Alain Wagner
Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent...
May 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515674/perioperative-management-of-patients-on-direct-oral-anticoagulants
#11
REVIEW
Virginie Dubois, Anne-Sophie Dincq, Jonathan Douxfils, Brigitte Ickx, Charles-Marc Samama, Jean-Michel Dogné, Maximilien Gourdin, Bernard Chatelain, François Mullier, Sarah Lessire
Direct oral anticoagulants (DOACs) have been licensed worldwide for several years for various indications. Each year, 10-15% of patients on oral anticoagulants will undergo an invasive procedure and expert groups have issued several guidelines on perioperative management in such situations. The perioperative guidelines have undergone numerous updates as clinical experience of emergency management has increased and perioperative studies including measurement of residual anticoagulant levels have been published...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28509761/dabigatran-in-nonvalvular-atrial-fibrillation-from-clinical-trials-to-real-life-experience
#12
Nicola Mumoli, Daniela Mastroiacovo, Eleonora Tamborini-Permunian, Josè Vitale, Matteo Giorgi-Pierfranceschi, Marco Cei, Francesco Dentali
: Atrial fibrillation is the most common arrhythmia in over-midlife patients. In addition to systolic heart failure, cerebral thromboembolism represents the most dramatic complication of this rhythm disorder, contributing to morbidity and mortality. Traditionally, anticoagulation has been considered the main strategy in preventing stroke and systemic embolism in atrial fibrillation patients and vitamin K-dependent antagonists have been widely used in clinical practice. Recently, the development of direct oral anticoagulants has certainly improved the management of this disease, providing, for the first time, the opportunity to go beyond vitamin K-dependent antagonists limits...
July 2017: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/28471371/the-reversal-of-direct-oral-anticoagulants-in-animal-models
#13
Markus Honickel, Necib Akman, Oliver Grottke
Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity)...
August 2017: Shock
https://www.readbyqxmd.com/read/28460624/dabigatran-metabolism-pharmacologic-properties-and-drug-interactions
#14
Nebojsa Antonijevic, Ivana Zivkovic, Ljubica Jovanovic, Dragan Matic, Mladen Kocica, Igor Mrdovic, Vladimir Kanjuh, Milica Culafic
The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration...
April 26, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28455651/-management-of-hemorrhage-in-patients-treated-with-direct-oral-anticoagulants
#15
REVIEW
O Grottke, H Lier, S Hofer
The introduction of nonvitamin K antagonistic, direct oral anticoagulants (DOAC) made thromboembolic prophylaxis easier for patients. For many physicians, however, there is still uncertainty about monitoring, preoperative discontinuation, and restarting of DOAC therapy. Guidelines for the management of bleeding are provided, but require specific therapeutic skills in the management of diagnostics and therapy of acute hemorrhage. Small clinical studies and case reports indicate that unspecific therapy with prothrombin complex concentrates (PCC) and activated PCC (aPCC) concentrate may reverse DOAC-induced anticoagulation...
April 28, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28439778/dabigatran-etexilate-appropriate-use-in-patients-with-chronic-kidney-disease-and-in-the-elderly-patients
#16
REVIEW
Mauro Molteni, Mario Bo, Giovanni Di Minno, Giuseppe Di Pasquale, Simonetta Genovesi, Danilo Toni, Paolo Verdecchia
Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved for the treatment of non-valvular atrial fibrillation (AF), and for the prevention and treatment of venous thromboembolism (VTE). Despite large randomized clinical trials and independent observational studies providing robust data concerning DE safety and efficacy, some physicians still perceive mild-to-moderate renal impairment and old age as a relative contraindication to its use. In this article, we review the available scientific evidence supporting the use of DE in these clinical situations...
April 24, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28429198/managing-the-perioperative-patient-on-direct-oral-anticoagulants
#17
Jordan Leitch, Janet van Vlymen
PURPOSE: Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery...
June 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28426914/the-recommended-dose-of-idarucizumab-may-not-always-be-sufficient-for-sustained-reversal-of-dabigatran
#18
A Simon, H Domanovits, C Ay, G Sengoelge, J H Levy, A O Spiel
Essentials Reversal of anticoagulant effects of dabigatran may occur despite application of idarucizumab. Monitoring of dabigatran level after antidote application is crucial to detect rebound. Repeated doses of idarucizumab may be necessary in cases of massive dabigatran accumulation. Combination of antidote application and renal replacement therapy may offer additional benefit. SUMMARY: Idarucizumab is a monoclonal antibody fragment designed for reversing the anticoagulant effects of dabigatran...
April 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28392512/direct-oral-anticoagulants-for-the-treatment-of-venous-thromboembolism-in-japan
#19
Mashio Nakamura, Norikazu Yamada, Masaaki Ito
Direct oral anticoagulants (DOACs) were developed to compensate for the demerits of warfarin. In Japan, three factor Xa inhibitors are used for the treatment of venous thromboembolism (VTE): edoxaban, rivaroxaban, and apixaban. Despite problems, such as the inability to monitor their effect and the lack of an antidote, these inhibitors have the same efficacy as conventional treatment with warfarin, and they are associated with a significantly high degree of safety in relation to hemorrhagic complications. East Asians, including Japanese, suffer from hemorrhage more frequently; therefore, DOACs are considered to be highly effective...
June 1, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28390791/edoxaban-how-does-the-newest-agent-fit-into-the-doac-landscape
#20
REVIEW
Caitlin M Gibson, Shannon W Finks
Edoxaban is the most recently approved factor Xa inhibitor within the class of direct oral anticoagulants (DOACs). Like other DOACs, edoxaban was approved by the US Food and Drug Administration for treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Similar to other DOACs, edoxaban has fewer drug-drug interactions than warfarin and does not require routine laboratory monitoring. Unlike other DOACs, edoxaban has yet to be approved for secondary or postoperative venous thromboembolism thromboprophylaxis...
August 2017: American Journal of Medicine
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