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Anticoagulation antidotes

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https://www.readbyqxmd.com/read/28198201/clinical-implications-of-reversal-agents-for-direct-oral-anticoagulants
#1
Sarah Monagle, John W Eikelboom, Kuan H Ng, Vinai C Bhagirath
Direct oral anticoagulants (DOACs) are effective in preventing and treating venous thromboembolism, and preventing stroke in atrial fibrillation. Until recently, there has been no specific reversal agent for DOACs. Now, a specific antidote for the direct thrombin inhibitor, dabigatran has been approved for use, and antidotes for factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are being developed. We review the evidence for currently used and emerging reversal strategies, and discuss possible clinical implications, including increased prescription of DOACs, use of DOACs in clinical situations previously felt to pose too great a risk of bleeding, and use of reversal agents beyond currently approved indications...
March 2017: Future Cardiology
https://www.readbyqxmd.com/read/28175444/176%C3%A2-andexanet-alfa-an-investigational-universal-antidote-for-reversal-of-anticoagulation-of-factor-xa-inhibitors-in-healthy-human-volunteers
#2
Florie Mar, Mark Crowther, Alex Gold, Genmin Lu, Janet Leeds, Brian Wiens, Vandana Mathur, Janice Castillo, Pamela Conley, Stuart Connolly, John Curnutte
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28167634/management-of-patients-on-non-vitamin-k-antagonist-oral-anticoagulants-in-the-acute-care-and-periprocedural-setting-a-scientific-statement-from-the-american-heart-association
#3
Amish N Raval, Joaquin E Cigarroa, Mina K Chung, Larry J Diaz-Sandoval, Deborah Diercks, Jonathan P Piccini, Hee Soo Jung, Jeffrey B Washam, Babu G Welch, Allyson R Zazulia, Sean P Collins
Non-vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States...
February 6, 2017: Circulation
https://www.readbyqxmd.com/read/28106485/management-strategies-for-atrial-fibrillation
#4
Peysh A Patel, Noman Ali, Andrew Hogarth, Muzahir H Tayebjee
Atrial fibrillation is the most prevalent cardiac arrhythmia, affecting 10% of those aged over 80 years. Despite multiple treatment options, it remains an independent prognostic marker of mortality due to its association with clinical sequelae, particularly cerebrovascular events. Management can be broadly divided into treatment of the arrhythmia, via rhythm or rate control, and stroke thromboprophylaxis via anticoagulation. Traditional options for pharmacotherapy include negatively chronotropic drugs such as β-blockers, and/or arrhythmia-modifying drugs such as amiodarone...
January 2017: Journal of the Royal Society of Medicine
https://www.readbyqxmd.com/read/28102773/the-optimal-duration-of-anticoagulant-therapy-after-unprovoked-venous-thromboembolism-still-a-challenging-issue
#5
Giovanna Elmi, Giuseppe Di Pasquale, Raffaele Pesavento
As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists...
January 19, 2017: VASA. Zeitschrift Für Gefässkrankheiten
https://www.readbyqxmd.com/read/28051778/a-potential-antidote-a-prohemostatic-factor-xa-variant-for-reversal-of-direct-oral-anticoagulants
#6
James C Fredenburgh, Jeffrey I Weitz
No abstract text is available yet for this article.
November 11, 2016: Circulation Research
https://www.readbyqxmd.com/read/28034889/alteration-of-blood-clotting-and-lung-damage-by-protamine-are-avoided-using-the-heparin-and-polyphosphate-inhibitor-uhra
#7
Manu Thomas Kalathottukaren, Libin Abraham, Piyushkumar R Kapopara, Benjamin F L Lai, Rajesh A Shenoi, Federico I Rosell, Edward M Conway, Edward L G Pryzdial, James H Morrissey, Charles A Haynes, Jayachandran N Kizhakkedathu
Anticoagulant therapy associated bleeding and pathological thrombosis, pose serious risks to hospitalized patients. Both complications could be mitigated by developing new therapeutics that safely neutralize anticoagulant activity and inhibit activators of the intrinsic blood clotting pathway, such as polyphosphate (polyP) and extracellular nucleic acids. The latter strategy could reduce the use of anticoagulants, potentially decreasing bleeding events. However, previously described cationic inhibitors of polyP and extracellular nucleic acids, exhibit both non-specific binding and adverse effects on blood clotting that limit their use...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27988509/rivaroxaban-induced-gastrointestinal-bleeding-presenting-as-acute-colon-obstruction
#8
Merav Cohen, Hadar Nevo, Dan Hershko, Alexander Becker
Rivaroxaban is a member of the novel target-specific oral anticoagulants (TSOACs) family of drugs recently approved for the prevention and treatment of venous thromboembolism events. A major drawback of the drug is its potential for causing severe hemorrhagic events, which may be difficult to treat in an emergency setting due to lack of effective antidote. Here, we describe a case of acute gastrointestinal (GI) hemorrhage leading to complete colon obstruction in a patient treated with rivaroxaban. Summary and Key Messages: The case presented here demonstrates a chain of events originating from an unprovoked intramural bleeding in a patient using rivaroxaban, leading to an organized giant clot formation, and to complete colon obstruction...
December 15, 2016: Pharmacology
https://www.readbyqxmd.com/read/27933968/emissive-h-aggregates-of-an-ultrafast-molecular-rotor-a-promising-platform-for-sensing-heparin
#9
Niyati H Mudliar, Prabhat K Singh
Constructing "turn on" fluorescent probes for heparin, a most widely used anticoagulant in clinics, from commercially available materials is of great importance, but remains challenging. Here, we report the formation of a rarely observed emissive H-aggregate of an ultrafast molecular rotor dye, Thioflavin-T, in the presence of heparin, which provides an excellent platform for simple, economic and rapid fluorescence turn-on sensing of heparin. Generally, H-aggregates are considered as serious problem in the field of biomolecular sensing, owing to their poorly emissive nature resulting from excitonic interaction...
November 23, 2016: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/27920714/idarucizumab-as-antidote-to-intracerebral-hemorrhage-under-treatment-with-dabigatran
#10
Valentin Held, Philipp Eisele, Christoph C Eschenfelder, Kristina Szabo
BACKGROUND AND PURPOSE: Non-vitamin K anticoagulants (NOAC) such as dabigatran have become important therapeutic options for the prevention of stroke. Until recently, there were only nonspecific agents to reverse their anticoagulant effects in a case of emergency. Idarucizumab, an antibody fragment targeting dabigatran, is the first specific antidote for a NOAC to be approved, but real-world experience is limited. METHODS: We report two cases of patients on dabigatran with acute intracerebral hemorrhage who received idarucizumab...
September 2016: Case Reports in Neurology
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#11
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27911120/new-frontiers-in-anticoagulation-non-vitamin-k-oral-anticoagulants-in-stroke-prevention
#12
Valentina Arnao, Marianna Riolo, Antonino Tuttolomondo, Antonio Pinto, Brigida Fierro, Paolo Aridon
Non vitamin-K oral anticoagulants (NOACs) are direct and specific inhibitors of the coagulation factors IIa (dabigatran) and Xa (apixaban, rivaroxaban, edoxaban) which share many pharmacokinetic properties. However, indications are lacking regarding the use of NOACs during thrombolysis, surgery and bleeding events. Areas covered: In this paper, the authors retrospectively analyzed the relevant literature on the NOACs using the PubMed and Google Scholar databases. Expert commentary: Although warfarin is effective in cardioembolic stroke prevention, easier handling and more favorable risk-benefit profile often render NOACs a more preferable therapy choice for neurologists...
December 12, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27900867/-new-direct-oral-anticoagulants-actual-review
#13
Jana Michalcová, Miroslav Penka, Alena Buliková, Jiřina Zavřelová, Andrea Štěpařová
In recent years the options of anticoagulant/antithrombotic therapy have extended with new - direct oral anticoagulants, comprising direct thrombin inhibitors (dabigatran etexilate) and direct factor Xa inhibitors (rivaroxaban, apixaban). These agents represent another progress towards "the ideal antithrombotic drug", and thus towards a safe and effective antithrombotic therapy. The following article provides actual review and recommendations for clinical practice, including laboratory assessment and management of emergency situations...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27836741/guidelines-of-the-french-society-of-otorhinolaryngology-sforl-managing-epistaxis-under-coagulation-disorder-due-to-antithrombotic-therapy
#14
V Escabasse, E Bequignon, B Vérillaud, L Robard, J Michel, O Malard, L Crampette
OBJECTIVE: The authors present the guidelines of the French Society of Otorhinolaryngology concerning the management of epistaxis during antithrombotic therapy. METHODS: A review of the literature was performed by a multidisciplinary work group. Guidelines were drafted, then re-edited by a reading group independent of the work group to produce the final text. The proposed recommendations were graded A, B, C or expert opinion, on decreasing levels of evidence. RESULTS: Before any decision to modify antithrombotic treatment, it is recommended to screen for overdose and assess the risk of thrombosis...
November 8, 2016: European Annals of Otorhinolaryngology, Head and Neck Diseases
https://www.readbyqxmd.com/read/27789605/reversal-of-anticoagulation-and-management-of-bleeding-in-patients-on-anticoagulants
#15
Prajwal Dhakal, Supratik Rayamajhi, Vivek Verma, Krishna Gundabolu, Vijaya R Bhatt
Bleeding is the most common complication of all anticoagulants. Any bleeding patient on an anticoagulant should be risk-stratified based on hemodynamic instability, source of bleeding, and degree of blood loss. Although minor bleed may be managed with discontinuation of anticoagulant, major bleed may require transfusion of blood products and use of specific antidote. The residual effects of each anticoagulant may be monitored with distinct coagulation assay. Intravenous or oral vitamin K can reverse the effect of warfarin within 24 to 48 hours and is indicated for any bleeding, international normalized ratio of >10 or 4...
October 26, 2016: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/27766043/doacs-advances-and-limitations-in-real-world
#16
REVIEW
Lai Heng Lee
The group of new oral anticoagulants or NOACs, now termed direct oral anticoagulants or DOACs, with their favourable results from large scale phase III clinical trials, represent a major advancement and expanded armamentarium in antithrombotic therapy. Dabigatran, rivaroxaban, apixaban and edoxaban are now in clinical routine use for prevention and treatment of arterial and venous thrombotic diseases as addressed in their clinical trials. Usage of the DOACs is expected to increase as clinicians gain more experience and reassurance with data from the real world studies which are generally consistent with that from clinical trials...
2016: Thrombosis Journal
https://www.readbyqxmd.com/read/27765272/major-bleeding-complications-in-patients-treated-with-direct-oral-anticoagulants-one-year-observational-study-in-a-paris-hospital
#17
L Deville, M Konan, A Hij, L Goldwirt, O Peyrony, F Fieux, P Faure, I Madelaine, S Villiers, D Farge-Bancel, C Frère
Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex...
July 2016: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/27752290/reversal-of-direct-oral-anticoagulants-in-hemophilia-treatment-ash-meeting-2015
#18
Clemens Feistritzer, Stefan Schmidt
During the 57(th) annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted...
2016: Memo
https://www.readbyqxmd.com/read/27742998/neutralization-of-ep217609-a-new-dual-action-fiia-fxa-anticoagulant-by-its-specific-antidote-avidin-a-phase-i-study
#19
P Gueret, S Combe, C Krezel, E Fuseau, P L M van Giersbergen, M Petitou, E Neuhart
INTRODUCTION: EP217609 is a representative of a new class of synthetic parenteral anticoagulants with a dual mechanism of action. It combines in a single molecule a direct thrombin inhibitor and an indirect factor Xa inhibitor. EP217609 can be neutralized by a specific antidote avidin, which binds to the biotin moiety of EP217609. PURPOSE: The primary objective was to assess the neutralization of EP217609 by avidin in healthy subjects. Secondary objectives were to define the optimal avidin monomer/EP217609 molar ratio to achieve an adequate neutralization of EP217609 and to assess the safety and tolerability of EP217609 and avidin...
January 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27736370/in-vitro-evaluation-of-aptamer-based-reversible-inhibition-of-anticoagulant-activated-protein-c-as-a-novel-supportive-hemostatic-approach
#20
Nasim Shahidi Hamedani, Heiko Rühl, Julia Janina Zimmermann, Tim Heiseler, Johannes Oldenburg, Günter Mayer, Bernd Pötzsch, Jens Müller
Activated protein C (APC) is a critical regulator of thrombin formation and thereby protects against thrombosis. On the other hand, overwhelming formation of APC increases the risk of bleeding such as in trauma-induced coagulopathy. Thus, pharmacological inhibition of APC activity may improve blood clottability in certain clinical situations. In this study, we demonstrate that the DNA aptamer HS02-52G binds with fast onset (1.118 ± 0.013 × 10(5) M(-1) s(-1)) to APC and possesses a long residence time of 13...
October 13, 2016: Nucleic Acid Therapeutics
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