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Anticoagulation antidotes

Zdeňka Hajšmanová, Pavla Šigutová, Alena Lavičková
Idarucizumab is designed to reverse the anticoagulant effect of dabigatran. This case report describes the administration of three independent doses of idarucizumab to a 76-year-old man suffering from atrial flutter being treated with dabigatran to prevent ischaemic stroke. The last dose of dabigatran was administered in the morning of the same day the patient was transferred to hospital because of the need for urgent pericardium puncture. Baseline dTT (dilute thrombin time) reached 700 ng/mL as glomerular filtration (GF) dropped to 0...
February 2018: Hämostaseologie
Kevin Fortier, Deepti Shroff, Uday N Reebye
BACKGROUND: Dabigatran, rivaroxaban, apixaban and edoxaban are approved novel oral anticoagulants (NOACs) as alternatives to Vitamin K antagonists (VKA). Physicians are prescribing an ever-increasing amount these drugs to their patients due to various advantages over existing medications. AIMS: The objective of this review is to provide the dental professional with current literature surrounding the emergence of NOACs, as well as various case studies on the subject, in an effort to guide clinical decision making regarding these medications...
February 28, 2018: Gerodontology
Hany S Abed, Michael J Kilborn, Vivien Chen, Raymond W Sy
The incidence and prevalence of atrial fibrillation (AF) is expected to more than double between 2010 and 2030. Accordingly, the use of non-vitamin K oral anticoagulant (NOAC) agents for thromboembolic stroke prevention is anticipated to increase. The development of effective and safe antidotes is needed to address the unmet need for rapid anticoagulation reversal. The immediate role for these novel antidotes is for reversal of NOAC activity in life threatening bleeding and urgent surgical intervention. In addition, reversal agents may play an important role in simplifying bridging protocols in the peri-procedural period for catheter ablation of AF and elective surgery...
December 2017: Journal of Atrial Fibrillation
Bryan D Hayes, Michael E Winters, Steve B Rosenbaum, Mohannad F Allehyani, Gary M Vilke
BACKGROUND: In 2010, the U.S. Food and Drug Administration (FDA) approved dabigatran as the first non-warfarin oral anticoagulant for use in the United States. At the time of FDA approval, there was no antidote or effective treatment for dabigatran-induced hemorrhage. In 2015, the FDA approved idarucizumab for the treatment of dabigatran-induced hemorrhage. The purpose of this clinical practice statement is to evaluate the role of select reversal agents in the management of patients with dabigatran-associated bleeding...
February 15, 2018: Journal of Emergency Medicine
Quentin Mathais, Pierre Esnault, Maximilien Cruc, Cedric Bernard, Bertrand Prunet, Pierre Emmanuel Gaillard
BACKGROUND: While spontaneous spinal epidural hematomas are rare, one of the identified risk factors is vitamin K antagonist therapy. CASE DESCRIPTION: We present a case of a spontaneous spinal epidural hematoma occurring in a patient under treatment with dabigatran, a non-vitamin K oral anticoagulant. The initial hemiparesis symptom was misleading and was retrospectively identified as Brown Sequard syndrome. Immediate dabigatran antagonism with idarucizumab followed by posterior cervical laminectomy permitted a complete neurological recovery at day 4...
February 6, 2018: World Neurosurgery
Weifeng Zhao, Qiang Liu, Xiang Zhang, Baihai Su, Changsheng Zhao
Heparin-based anticoagulant drugs are widely used for the prevention of blood clotting during extracorporeal circuit (bloodlines or cassette system) and surgical procedures as well as for the treatment of thromboembolic events. However, these anticoagulants are associated with bleeding risks that demand continuous monitoring and neutralization with antidotes. We explore the possibility of utilizing anticoagulants for blood clotting prevention, then removing them before transfusing the blood back to body, thus avoid bleeding risks...
February 2, 2018: Colloids and Surfaces. B, Biointerfaces
Elsa P Bianchini, Alexandre Sebestyen, Toufik Abache, Yasmine Bourti, Alexandre Fontayne, Vincent Richard, Fabienne Tamion, Jean-Luc Plantier, Fabien Doguet, Delphine Borgel
Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant inactive antithrombin (riAT) was designed as an antidote to heparin and was previously shown to be as potent as protamine in-vitro. In the present study, riAT was assessed for its ability to neutralize heparin after CPB in a rat model. After 60 min of CPB under heparin, rats received 5 mg/kg protamine, 37.5 mg/kg riAT or phosphate buffered saline (PBS) as placebo...
January 24, 2018: British Journal of Haematology
Jerrold H Levy, James Douketis, Jeffrey I Weitz
The non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban, and rivaroxaban, which inhibit coagulation factor Xa. Although clinical studies of NOACs were conducted without antidotes, patient outcomes with major bleeding when receiving NOACs were no worse than those in patients treated with a vitamin K antagonist. Nonetheless, in patients with life-threatening bleeding or requiring urgent surgery, the capacity for rapid NOAC reversal is likely to increase patient safety...
January 18, 2018: Nature Reviews. Cardiology
Sean T Chen, Manesh R Patel
In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulation is important for prevention of stroke and systemic embolism (SE). While Vitamin K antagonists (VKAs) have historically been the standard of care, these medications are limited by numerous food and drug interactions with onerous requirements for frequent monitoring and dose adjustments. Over the past decade, several novel oral anticoagulants (NOACs) have been developed to directly inhibit factor IIa/thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban, edoxaban)...
January 13, 2018: Progress in Cardiovascular Diseases
George D Katritsis, Demosthenes G Katritsis
Oral anticoagulation is mandatory for patients at high risk of thromboembolism, but the risk of bleeding should also be taken into account. Direct oral anticoagulants are now recommended for non-valvular AF as a potential alternative to warfarin. In this article we discuss methods to assess the anticoagulant effect of these agents, specific and general antidotes, and management of complications such as embolic and haemorrhagic stroke, and significant bleeding.
December 2017: Arrhythmia & Electrophysiology Review
Upinder Kaur, Sankha Shubhra Chakrabarti, Sukdev Manna, Indrajeet Singh Gambhir
Dabigatran is a newer oral direct thrombin inhibitor approved by the United States Food and Drug Administration and the European Medicines Agency (EMA). The proper dosage of the drug, the potential for adverse drug reactions and the nature of bleeds with use of this drug as with other novel oral anticoagulants (NOACs), in the elderly population are still areas of uncertainty. Despite the existence of a specific antibody, idarucizumab which is an antidote to dabigatran toxicity, management of dabigatran-induced bleeds is an undefined area especially in resource constrained settings...
January 2018: Therapeutic Advances in Drug Safety
Anna Plitt, Sameer Bansilal
The nonvitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban are used for the reduction of the risk of stroke or systemic embolism (SEE) in patients with nonvalvular atrial fibrillation (NVAF). The purpose of this review is to highlight the safety and efficacy results of the pivotal NOAC clinical trials for use in NVAF, discuss some of the unique management challenges in the use of NOACs in special populations, summarize data on emerging and novel indications, and address potential future directions...
February 2017: Journal of Atrial Fibrillation
Willemijn J Comuth, Anne-Mette Haase, Linda Ø Henriksen, Jerzy Malczynski, Daan van de Kerkhof, Anna-Marie B Münster
Idarucizumab, an antidote specific for dabigatran, became available recently. Dabigatran is not associated with increased risk of hepatotoxicity in comparison with warfarin, but it is seen as a rare side-effect. Cases of cholestatic liver injury due to dabigatran have not been reported previously. We present a case of severe gastro-intestinal bleeding with underlying dabigatran intoxication in a patient with renal failure and the effect of reversal of dabigatran using idaruzicumab on coagulation assays. International normalized ratio (INR) and activated partial thromboplastin time (APTT) results were elevated in a setting of sepsis, possibly due to liver failure...
November 17, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
Clemens Küpper, Lars Kellert, Steffen Tiedt, Frank Arne Wollenweber
Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only...
November 8, 2017: Fortschritte der Neurologie-Psychiatrie
Scott Kaatz, Charles E Mahan, Asaad Nakhle, Kulothungan Gunasekaran, Mahmoud Ali, Robert Lavender, David G Paje
PURPOSE OF REVIEW: The purpose of this review was to offer practical management strategies for when patients receiving direct oral anticoagulants require elective surgery or present with bleeding complications. RECENT FINDINGS: Clinical practice guidelines are now available on the timing of periprocedural interruption of treatment with the newer direct oral anticoagulants based on their pharmacodynamics and pharmacokinetics and based on findings from cohort studies and clinical trials...
October 24, 2017: Current Cardiology Reports
Nobuhiko Arai, Yutaka Mine, Hiroshi Kagami, Michiyuki Maruyama, Atsushi Daikoh, Makoto Inaba
BACKGROUND: Chronic subdural hematoma (CSDH) is a common intracranial hematoma. The number of patients who undergo anticoagulant therapy including a direct oral anticoagulant (DOAC) is expected to increase. Recently, idarucizumab, the antidote for dabigatran, which is a DOAC, has been developed. We successfully treated CSDH with dabigatran using emergency burr hole surgery and idarucizumab. CASE DESCRIPTION: A 79-year-old Japanese man severely hit his head and visited the emergency department...
January 2018: World Neurosurgery
Quintin W Hughes, Bao T Le, Grace Gilmore, Ross I Baker, Rakesh N Veedu
Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and tertiary conformations based on Watson-Crick base-pairing interactions and can be used to target a range of different molecules. Two aptamers, HD1 and HD22, that bind to exosites I and II of the human thrombin molecule, respectively, have been extensively studied due to their anticoagulant potentials. However, a fundamental issue preventing the clinical translation of many aptamers is degradation by nucleases and reduced pharmacokinetic properties requiring higher dosing regimens more often...
October 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Francesca Cortese, Giacinto Calculli, Michele Gesualdo, Annagrazia Cecere, Annapaola Zito, Fiorella De Vito, Rossella Carbonara, Santa Carbonara, Anna Maria Cortese, Marco Matteo Ciccone
BACKGROUND: Idarucizumab, a humanized monoclonal antibody fragment acting as a specific antidote for dabigatran, is approved for reversing the dabigatran-associated possible bleeding from critical sites or bleeding persisting despite local post-procedure haemostasis. Moreover, it can also be applied to reverse the dabigatran anticoagulant activity in emergency surgery or in other invasive procedure at high risk of bleeding. OBJECTIVE: In this study, we discuss idarucizumab in light of the available literature data by conducting extensive research in the PubMed, EMBASE and Cochrane Library on the topic, using idarucizumab, dabigatran and their combinations as Mesh terms, and focusing on high impact investigations...
2018: Current Drug Targets
Michela Giustozzi, Melina Verso, Giancarlo Agnelli, Cecilia Becattini
Major bleeding occurs in about 4% of patients while on treatment with direct oral anticoagulants (DOACs). The case-fatality rate associated with these events is estimated to be about 5%. The specific roles of antidotes, when used with DOACs in reducing the case fatality or improving the overall clinical course of these events, are not thoroughly understood. To this regard, the US Food and Drug Administration as well as European Medicines Agency have recently licensed idarucizumab for the management of patients with life-threatening bleeding or the need for urgent surgery/procedures while on treatment with dabigatran...
November 2017: Journal of Thrombosis and Thrombolysis
Mikhail S Dzeshka, Daniele Pastori, Gregory Y H Lip
The number of atrial fibrillation (AF) patients requiring thrombo-prophylaxis with oral anticoagulation is greatly increasing. The introduction of non-vitamin K oral anticoagulants (NOACs) in addition to standard therapy with dose-adjusted warfarin has increased the therapeutic options for AF patients. Despite a generally better safety profile of the NOACs, the risk of major bleedings still persists, and the management of serious bleeding is a clinical challenge. Areas covered: In the current review, risk of major bleeding in patients taking NOACs and general approaches to manage bleeding depending on severity, with a particular focus on specific reversal agents, are discussed...
November 2017: Expert Review of Hematology
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