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Anticoagulation antidotes

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https://www.readbyqxmd.com/read/28549534/dabigatran-reversal-in-a-patient-with-end-stage-liver-disease%C3%A2-and-acute-kidney-injury
#1
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
#2
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
#3
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...
May 23, 2017: Der Internist
https://www.readbyqxmd.com/read/28524847/an-in-vivo-strategy-to-counteract-post-administration-anticoagulant-activity-of-azido-warfarin
#4
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
#5
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
#6
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
#7
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 (VKA) 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)...
April 4, 2017: Shock
https://www.readbyqxmd.com/read/28460624/dabigatran-metabolism-pharmacologic-properties-and-drug-interactions
#8
Nebojsa Antonijevic, Ivana Zivkovic, Ljubica Jovanovic, Dragan Matic, Mladen Kocica, Igor Mrdovic, Vladimir Kanjuh, Milica Culafic
The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration...
April 26, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28455651/-management-of-hemorrhage-in-patients-treated-with-direct-oral-anticoagulants
#9
REVIEW
O Grottke, H Lier, S Hofer
The introduction of nonvitamin K antagonistic, direct oral anticoagulants (DOAC) made thromboembolic prophylaxis easier for patients. For many physicians, however, there is still uncertainty about monitoring, preoperative discontinuation, and restarting of DOAC therapy. Guidelines for the management of bleeding are provided, but require specific therapeutic skills in the management of diagnostics and therapy of acute hemorrhage. Small clinical studies and case reports indicate that unspecific therapy with prothrombin complex concentrates (PCC) and activated PCC (aPCC) concentrate may reverse DOAC-induced anticoagulation...
April 28, 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28439778/dabigatran-etexilate-appropriate-use-in-patients-with-chronic-kidney-disease-and-in-the-elderly-patients
#10
REVIEW
Mauro Molteni, Mario Bo, Giovanni Di Minno, Giuseppe Di Pasquale, Simonetta Genovesi, Danilo Toni, Paolo Verdecchia
Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved for the treatment of non-valvular atrial fibrillation (AF), and for the prevention and treatment of venous thromboembolism (VTE). Despite large randomized clinical trials and independent observational studies providing robust data concerning DE safety and efficacy, some physicians still perceive mild-to-moderate renal impairment and old age as a relative contraindication to its use. In this article, we review the available scientific evidence supporting the use of DE in these clinical situations...
April 24, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28429198/managing-the-perioperative-patient-on-direct-oral-anticoagulants
#11
Jordan Leitch, Janet van Vlymen
PURPOSE: Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery...
June 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28426914/recommended-dose-of-idarucizumab-may-not-always-be-sufficient-for-sustained-reversal-of-dabigatran
#12
Alexander Simon, Hans Domanovits, Cihan Ay, Gürkan Sengölge, Jerrold H Lewy, Alexander O Spiel
Idarucizumab is a monoclonal antibody fragment designed for reversing the anticoagulant effects of dabigatran. Administration is recommended as two intravenous boluses of 2.5 g within 15 minutes of each other or as a single 5 g bolus. However, in certain situations a second dose of the drug could be necessary. We report the case of a 77-year old man, treated with dabigatran for paroxysmal atrial fibrillation. He presented at our department with acute renal failure, concomitant massive dabigatran accumulation, and subsequent acute gastrointestinal bleeding...
April 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28392512/direct-oral-anticoagulants-for-the-treatment-of-venous-thromboembolism-in-japan
#13
Mashio Nakamura, Norikazu Yamada, Masaaki Ito
Direct oral anticoagulants (DOACs) were developed to compensate for the demerits of warfarin. In Japan, three factor Xa inhibitors are used for the treatment of venous thromboembolism (VTE): edoxaban, rivaroxaban, and apixaban. Despite problems, such as the inability to monitor their effect and the lack of an antidote, these inhibitors have the same efficacy as conventional treatment with warfarin, and they are associated with a significantly high degree of safety in relation to hemorrhagic complications. East Asians, including Japanese, suffer from hemorrhage more frequently; therefore, DOACs are considered to be highly effective...
April 7, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28390791/edoxaban-how-does-the-newest-agent-fit-into-the-doac-landscape
#14
REVIEW
Caitlin M Gibson, Shannon W Finks
Edoxaban is the most recently approved factor Xa inhibitor within the class of direct oral anticoagulants (DOACs). Like other DOACs, edoxaban was approved by the US Food and Drug Administration for treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Similar to other DOACs, edoxaban has fewer drug-drug interactions than warfarin and does not require routine laboratory monitoring. Unlike other DOACs, edoxaban has yet to be approved for secondary or postoperative venous thromboembolism thromboprophylaxis...
April 6, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28386620/direct-oral-anticoagulants-doac-management-of-emergency-situations-rationale-and-design-of-the-radoa-registry
#15
Edelgard Lindhoff-Last
The worldwide increase in the aging population and the associated increase in the prevalence of atrial fibrillation and venous thromboembolism as well as the widespread use of direct oral anticoagulants (DOAC) have resulted in an increase of the need for the management of bleeding complications and emergency operations in frail, elderly patients, in clinical practice. When severe bleeding occurs, general assessment should include evaluation of the bleeding site, onset and severity of bleeding, renal function, and concurrent medications with focus on antiplatelet drugs and nonsteroidal anti-inflammatory drugs (NSAID)...
April 6, 2017: Hämostaseologie
https://www.readbyqxmd.com/read/28364736/bleeding-complications-and-management-on-anticoagulant-therapy
#16
Sam Schulman
Patients treated with anticoagulants have an unavoidable risk of bleeding complications. There are, for all oral anticoagulants, several potential options for management of major bleeding. The first action is to assess the causative role of the anticoagulant in the current bleeding. Supportive measures have been assessed in several post hoc analyses of the phase III pivotal trials with the non-vitamin K antagonist oral anticoagulants (NOACs). Those results will be reviewed here together with emerging data on the efficacy and safety of the specific antidotes idarucizumab (for dabigatran) and andexanet-α (for factor Xa inhibitors)...
April 1, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28362649/rapid-and-well-tolerated-action-of-idarucizumab-for-antagonizing-dabigatran-in-a-patient-needing-urgent-thrombolysis-a-case-report
#17
Roberto Facchinetti, Giulia DeGuidi, Federica Pitoni, Giorgio Ricci, Giuseppe Lippi
Dabigatran is a direct oral anticoagulant drug exhibiting clinical benefits over vitamin K antagonists. A procedure for reversing the anticoagulant effect of direct oral anticoagulants may be needed in emergency clinical settings, and is traditionally accomplished by using plasma products or hemostatic physical interventions. Idarucizumab, a specific antidote for dabigatran, has recently become available. This compound can be rapidly administered by intravenous injection and is effective in reversing anticoagulation in few minutes...
March 30, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28320118/prothrombin-complex-concentrate-administration-for-bleeding-associated-with-non-vitamin-k-antagonist-oral-anticoagulants-the-samurai-nvaf-study
#18
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
#19
REVIEW
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...
April 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28270004/-the-first-use-of-iv-idarucizumab-for-dabigatran-reversal-in-hungary
#20
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
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