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Anticoagulation antidotes

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https://www.readbyqxmd.com/read/28320118/prothrombin-complex-concentrate-administration-for-bleeding-associated-with-non-vitamin-k-antagonist-oral-anticoagulants-the-samurai-nvaf-study
#1
Sohei Yoshimura, Shoichiro Sato, Kenichi Todo, Yasushi Okada, Eisuke Furui, Takayuki Matsuki, Hiroshi Yamagami, Masatoshi Koga, Jun C Takahashi, Kazuyuki Nagatsuka, Shoji Arihiro, Kazunori Toyoda
BACKGROUND: Antidotes appropriate for non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are not yet in widespread clinical use. Efficacy of prothrombin complex concentrate (PCC) in NOAC-associated bleeding remains unclarified. METHODS: Ten NOAC users (4 women, median 74years old) who developed major bleeding and received PCC were prospectively enrolled. Eight single-center NOAC users (0 women, median 74years old) with intracerebral hemorrhage, who over the same period did not receive PCC, were studied for comparison...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28282497/andexanet-alfa-for-the-reversal-of-anticoagulant-activity-in-patients-treated-with-direct-and-indirect-factor-xa-inhibitors
#2
Tarek Nafee, Aysha Aslam, Gerald Chi, Seyedmahdi Pahlavani, Dima Nimri, Aravind Reddy Kuchkuntla, Usama Talib, Nathan Michalak, Yazan Daaboul, Serge Korjian, Anthony Gallo, C Michael Gibson
Andexanet alfa is a recombinant factor Xa decoy molecule that inhibits direct and indirect factor Xa inhibitors to allow the normal coagulation process to resume. Its development arises in a space where novel oral anticoagulants are receiving expanded indications yet their use is limited by the lack of an effective reversal agent. Areas covered: This article reviews the biochemical properties, mechanism of action and the preclinical and clinical trials on andexanet alfa. It additionally aims to provide expert commentary and future perspectives on the efficacy, safety and challenges facing andexanet alfa as a universal antidote for direct and indirect factor Xa inhibitors...
March 22, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28270004/-the-first-use-of-iv-idarucizumab-for-dabigatran-reversal-in-hungary
#3
Lajos Driesz, Éva Barabás, Ildikó Bodócs, Zoltán Szántó, György Herr, Gábor Bencsik, László Pál, József Borbola
At present, the direct thrombin inhibitor dabigatran is the only one amongst the new direct anticoagulants which has an effective, specific reversal agent. The novel agent idarucizumab is a humanized, monoclonal antibody fragment binds to dabigatran within minutes thereby offers an opportunity to induce a safe, long-lasting reverse of the anticoagulant effects of dabigatran. The authors describe the first use of idarucizumab in Hungary (23. 05. 2016) in an old female patient with non-valvular paroxysmal atrial fibrillation of high stroke risk-score and renal dysfunction who was taking dabigatran (2 x 110 mg/day) when an acute abdomen developed requiring emergency cholecystectomy...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28265404/real-world-use-of-idarucizumab-for-dabigatran-reversal-in-three-cases-of-serious-bleeding
#4
Nicolas Gendron, Anne Laure Feral-Pierssens, Igor Jurcisin, Emmanuelle de Raucourt, Valerie Bouton, Anne Marie Fischer, Camille Lorenceau-Savale, Agnès Lillo-Le Louët, David M Smadja
Bleeding is a rare complication of direct oral anticoagulant potentially associated with high mortality rates. Biological monitoring is necessary for more than 24 h after idarucizumab antidote therapy in case of bleeding with dabigatran therapy.
March 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28255372/upper-gastrointestinal-endoscopy-in-emergency-setting-for-patients-receiving-oral-anticoagulants-practice-updates
#5
REVIEW
R Oprita, B Oprita, B Diaconescu, M R Bratu, D Berceanu
Anticoagulants are frequently used medications in diverse cardiovascular diseases. Their uses highly increase the risk of bleeding from upper and lower gastrointestinal sources, whether there is a classic vitamin K antagonist or a novel oral anticoagulant. Their interruption can promote procoagulation status with different thromboembolic accidents. Discontinuation of oral anticoagulants before the elective procedures is standardized but there are no guidelines for managing bleeding lesions of upper gastrointestinal tract concomitant with anticoagulation...
January 2017: Journal of Medicine and Life
https://www.readbyqxmd.com/read/28239301/the-reversal-effect-of-prothrombin-complex-concentrate-pcc-activated-pcc-and-recombinant-activated-factor-vii-against-anticoagulation-of-xa-inhibitor
#6
Nina Haagenrud Schultz, Hoa Thi Tuyet Tran, Stine Bjørnsen, Carola Elisabeth Henriksson, Per Morten Sandset, Pål Andre Holme
BACKGROUND: An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28198201/clinical-implications-of-reversal-agents-for-direct-oral-anticoagulants
#7
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
#8
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
#9
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
#10
REVIEW
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
#11
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
#12
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
#13
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 nonspecific binding and adverse effects on blood clotting that limit their use...
March 9, 2017: Blood
https://www.readbyqxmd.com/read/27988509/rivaroxaban-induced-gastrointestinal-bleeding-presenting-as-acute-colon-obstruction
#14
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...
2017: Pharmacology
https://www.readbyqxmd.com/read/27933968/emissive-h-aggregates-of-an-ultrafast-molecular-rotor-a-promising-platform-for-sensing-heparin
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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