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Complications of Anticoagulants and Blood Transfusion
Published in Stephen M. Cohn, Matthew O. Dolich, Complications in Surgery and Trauma, 2014
Ara J. Feinstein, Mohan Ramalingam
Lepirudin and Bivalirudin are derived from hirudin, an anticoagulant that was first derived from leeches. Bivalirudin reversibly binds to the active and secondary binding sites of thrombin and is approved for use in coronary procedures. Argatroban is a synthetic direct thrombin inhibitor that is also approved for treating HIT, and its clearance is primarily hepatic. Dabigatran, like argatroban, directly inhibits both free and clotbound thrombin and is approved for treating nonvalvular atrial fibrillation.18
Epidural and intrathecal analgesia
Published in Pamela E. Macintyre, Stephan A. Schug, Acute Pain Management, 2014
Pamela E. Macintyre, Stephan A. Schug
Dabigatran is an oral anticoagulant used primarily in patients with atrial fibrillation. As with fondaparinux, there are significant concerns about the safety of epidural techniques. Again difficulties in reversal and prolonged duration of effect (which is even longer in patients with renal impairment) create uncertainty about its safe use. Dabigatran should be discontinued 7 days before epidural or spinal blocks are performed and epidural catheters should be removed 6 hours before the drug is restarted.
D
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Dabigatran etexilate is a prodrug which does not exhibit any pharmacological activity. After oral administration, dabigatran etexilate is rapidly absorbed and converted to dabigatran by esterase-catalysed hydrolysis in plasma and in the liver. Dabigatran is a potent, competitive, reversible direct thrombin inhibitor and is the main active principle in plasma.
Thrombin-induced platelet aggregation −effect of dabigatran using automated platelet aggregometry−
Published in Platelets, 2020
Mie Shimizu, Tatsunori Natori, Keisuke Tsuda, Makiko Yoshida, Asami Kamada, Kiyotaka Oi, Yoko Ishigaku, Kazumasa Oura, Shinsuke Narumi, Masahiro Yamamoto, Yasuo Terayama
Unfractionated heparin, low-molecular-weight heparin, and direct thrombin inhibitors such as lepirudin, argatroban, bivalirudin, and dabigatran, unlike PAR1 antagonists, are anticoagulants rather than specific antiplatelet drugs. However, the inhibition of thrombin results in less platelet activation via PAR-1 on human platelets [19,20]. Dabigatran is a direct thrombin inhibitor that is used to decrease the risk of ischemic stroke in patients with atrial fibrillation [21]. In an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial, reductions in ischemic stroke and bleeding outcomes correlated with dabigatran plasma concentrations [22]. Although dabigatran is administered twice a day, the timing of peak and trough plasma concentrations of dabigatran is not fully understood. Factors such as renal function, age, and sex may contribute to differences in plasma concentrations of dabigatran between individuals [22,23]. Renal function is a major determinant of trough dabigatran concentrations, which correlate with the risk of thromboembolic and hemorrhagic outcomes [24,25]. A report by Terayama [26] indicated that effects on cerebrovascular events may differ between direct thrombin inhibitors and Factor Xa inhibitors. Direct thrombin inhibitors may play important roles in preventing atherothrombosis and reducing intracerebral hemorrhage and atherothrombotic events, but suitable tests to investigate the effects of dabigatran have yet to be developed.
Incomplete dabigatran reversal with idarucizumab
Published in Clinical Toxicology, 2018
Aaron P. Steele, Jin A. Lee, William E. Dager
Dabigatran is an oral competitive direct thrombin inhibitor used for prevention of stroke in patients with non-valvular atrial fibrillation (AF), as well as prevention and treatment of acute thromboembolism [1]. Dabigatran offers an attractive alternative for long-term anticoagulation due to a lower incidence of intracranial bleed when compared to warfarin in clinical trials; however, a lack of readily accessible methods to measure degree of anticoagulation and unavailability of an effective reversal agent raised concerns for patients who experienced bleeding events or required urgent procedures. In October 2015, the U.S. Food and Drug Administration (FDA) approved idarucizumab, a humanized monoclonal antibody fragment that binds directly to dabigatran and its metabolites, directly neutralizing its anticoagulant effects. The 5 g dose selected for the REVERSE-AD trial was based on its predicted ability to fully neutralize the dabigatran concentrations observed in 99% of patients in the RE-LY trial [2]. However, patients who present with extremely elevated concentrations are not reflective of the original study population. Like any antidote, a limit may exist in how much drug can be neutralized with a fixed dose. We present two cases illustrating incomplete reversal of excessively elevated dabigatran serum concentrations despite full doses of idarucizumab.
Biopharmaceutics considerations for direct oral anticoagulants
Published in Drug Development and Industrial Pharmacy, 2021
Rafael Pereira de Andrade, Tamires Guedes Caldeira, Bárbara Vasconcelos Vasques, André Luís Morais Ruela, Jacqueline de Souza
Dabigatran is a potent, specific and reversible inhibitor of free and clot-associated thrombin, which acts by binding to the active site of the serine protease [36]. It was the first DOAC approved by the European Union and FDA in 2008 and 2010, respectively, being indicated for the prevention of stroke, systemic embolism, and treatment of VTE and PE [37,38]. It is marketed as Pradaxa®, in capsules at doses of 75, 110, and 150 mg (expressed as dabigatran etexilate), a salt (mesylate) of a prodrug (etexilate). However, the highest single dose administered is 220 mg, indicated for the prophylaxis of VTE and PE in individuals undergoing hip replacement surgery [39].