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Anticoagulation antidotes

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https://www.readbyqxmd.com/read/28913672/reversal-of-dabigatran-associated-bleeding-using-idarucizumab-review-of-the-current-evidence
#1
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...
September 14, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28901221/direct-oral-anticoagulant-reversal-how-when-and-issues-faced
#2
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...
September 13, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28898791/overlooked-complication-of-anticoagulant-therapy-the-intramural-small-bowel-hematoma-a-case-report
#3
J M Pimenta, S Raluca, J Pimenta de Castro, L 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...
September 1, 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
#4
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 non-toxic nature...
September 7, 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
#5
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...
August 14, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28790786/direct-acting-oral-anticoagulant-bench-to-bedside
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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