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Anticoagulation antidotes

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https://www.readbyqxmd.com/read/29148292/cholestatic-liver-injury-as-a-side-effect-of-dabigatran-and-the-use-of-coagulation-tests-in-dabigatran-intoxication-and-after-reversal-by-idarucizumab-in-bleeding-and-sepsis
#1
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
https://www.readbyqxmd.com/read/29117605/-new-oral-anticoagulants-noac-in-stroke-treatment
#2
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
https://www.readbyqxmd.com/read/29064044/management-of-elective-surgery-and-emergent-bleeding-with-direct-oral-anticoagulants
#3
REVIEW
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
https://www.readbyqxmd.com/read/29054780/safe-burr-hole-surgery-for-chronic-subdural-hematoma-using-dabigatran-with-idarucizumab
#4
Nobuhiko Arai, Yutaka Mine, Hiroshi Kagami, Michiyuki Maruyama, Jun Daiko, 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 room (ER)...
October 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29048375/construction-of-a-bivalent-thrombin-binding-aptamer-and-its-antidote-with-improved-properties
#5
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
https://www.readbyqxmd.com/read/28950812/idarucizumab-what-should-we-know
#6
Francesca Cortese, 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 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 manuscript, 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 as Mesh terms idarucizumab, dabigatran and their combinations, and focusing on high impact investigations...
September 25, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28913672/reversal-of-dabigatran-associated-bleeding-using-idarucizumab-review-of-the-current-evidence
#7
REVIEW
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
https://www.readbyqxmd.com/read/28901221/direct-oral-anticoagulant-reversal-how-when-and-issues-faced
#8
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
https://www.readbyqxmd.com/read/28898791/overlooked-complication-of-anticoagulant-therapy-the-intramural-small-bowel-hematoma-a-case-report
#9
Joana Marantes Pimenta, Raluca Saramet, João Pimenta de Castro, Luís Gabriel Pereira
INTRODUCTION: Intramural small bowel hematoma is a rare, and often overlooked consequence of anticoagulant therapy. In this report we present such a case in order to bring forth awareness to this entity, and its management. PRESENTATION OF CASE: We report a 81-year old male who presented with abdominal pain for 2days. He had been under anticoagulant therapy with warfarin for 9 years, presenting with an elevated INR of 6,2. Intramural small bowel hematoma was confirmed with abdominal ultrasound and CT scan...
2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28880550/a-polymer-therapeutic-having-universal-heparin-reversal-activity-molecular-design-and-functional-mechanism
#10
Manu Thomas Kalathottukaren, Srinivas Abbina, Kai Yu, Rajesh A Shenoi, A Louise Creagh, Charles Haynes, Jayachandran N Kizhakkedathu
Heparins are widely used to prevent blood clotting during surgeries and for the treatment of thrombosis. However, bleeding associated with heparin therapy is a concern. Protamine, the only approved antidote for unfractionated heparin (UFH) could cause adverse cardiovascular events. Here, we describe a unique molecular design used in the development of a synthetic dendritic polycation named as universal heparin reversal agent (UHRA), an antidote for all clinically used heparin anticoagulants. We elucidate the mechanistic basis for the selectivity of UHRA to heparins and its nontoxic nature...
September 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28808918/idarucizumab-in-dabigatran-treated-patients-with-acute-ischemic-stroke-receiving-alteplase-a-systematic-review-of-the-available-evidence
#11
REVIEW
Slaven Pikija, Laszlo K Sztriha, J Sebastian Mutzenbach, Stefan M Golaszewski, Johann Sellner
BACKGROUND AND PURPOSE: Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke...
September 2017: CNS Drugs
https://www.readbyqxmd.com/read/28790786/direct-acting-oral-anticoagulant-bench-to-bedside
#12
REVIEW
D S Chadha, P Bharadwaj
Vitamin K antagonists are an effective group of oral anticoagulants. However because of genetic variability in their metabolism and multiple food and drug interactions, these drugs have narrow therapeutic window with unpredictable anticoagulant effects requiring constant monitoring. Several newer direct acting oral anticoagulants have been approved for prevention of stroke in patients with nonvalvular atrial fibrillation and treatment or prevention of venous thromboembolism. The direct acting oral anticoagulants include the direct thrombin inhibitor (dabigatran) and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban)...
July 2017: Medical Journal, Armed Forces India
https://www.readbyqxmd.com/read/28741113/approaches-to-prevent-bleeding-associated-with-anticoagulants-current-status-and-recent-developments
#13
REVIEW
Manu Thomas Kalathottukaren, Charles A Haynes, Jayachandran N Kizhakkedathu
Anticoagulants are widely used for the prophylaxis and treatment of cardiovascular disorders and to prevent blood clotting during surgeries. However, the major limitation associated with anticoagulant therapy is bleeding; all the current anticoagulants do have a bleeding risk. The propensity to bleed is much higher among the elderly population and patients with renal insufficiency. Therefore, there is an utmost and urgent clinical need for a highly efficient, nontoxic antidote with excellent anticoagulant reversal activity...
July 24, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28673500/-state-of-the-art-direct-oral-anticoagulants-and-transfusion
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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