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Reversal agents for novel anticoagulants

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https://www.readbyqxmd.com/read/28282497/andexanet-alfa-for-the-reversal-of-anticoagulant-activity-in-patients-treated-with-direct-and-indirect-factor-xa-inhibitors
#1
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 10, 2017: Expert Review of Cardiovascular Therapy
https://www.readbyqxmd.com/read/28277769/reversal-of-direct-oral-anticoagulants
#2
X-Y Zhang, M J Desborough, S Shapiro
An understanding of how to counteract the anticoagulant effect of direct oral anticoagulants is essential in the event of haemorrhage, emergency surgery and overdose. This review summarizes strategies for the reversal of direct oral anticoagulants, including the use of novel agents.
March 2, 2017: British Journal of Hospital Medicine
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/28210454/managing-patients-taking-edoxaban-in-dentistry
#4
REVIEW
Adrian Curto, Daniel Curto, Jorge Sanchez
BACKGROUND: Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life...
February 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28097231/protein-disulfide-isomerase-inhibition-blocks-thrombin-generation-in-humans-by-interfering-with-platelet-factor-v-activation
#5
Jack D Stopa, Donna Neuberg, Maneka Puligandla, Bruce Furie, Robert Flaumenhaft, Jeffrey I Zwicker
BACKGROUND: Protein disulfide isomerase (PDI) is required for thrombus formation. We previously demonstrated that glycosylated quercetin flavonoids such as isoquercetin inhibit PDI activity and thrombus formation in animal models, but whether extracellular PDI represents a viable anticoagulant target in humans and how its inhibition affects blood coagulation remain unknown. METHODS: We evaluated effects of oral administration of isoquercetin on platelet-dependent thrombin generation in healthy subjects and patients with persistently elevated anti-phospholipid antibodies...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/27803506/role-of-novel-oral-anticoagulants-in-the-treatment-of-antiphospholipid-syndrome
#6
C Whitney White, Angela R Thomason, Katie Boyd
Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombosis or pregnancy loss with persistent positive antibodies. Standard treatment for APS with history of thromboembolism is heparin or low-molecular-weight heparin followed by a vitamin K antagonist (VKA). Novel oral anticoagulants (NOACs) could be effective in patients with APS, but none carry indications for treatment related to APS. Clinical Evidence: Five case reports or series with rivaroxaban and dabigatran suggest thrombotic events occur most often in the higher risk population (arterial thrombosis and/or triple positive antibodies) or in patients who had recurrent VTEs on warfarin therapy...
October 2016: Hospital Pharmacy
https://www.readbyqxmd.com/read/27727040/idarucizumab-for-reversal-of-dabigatran-associated-bleeding-misnomer-or-miracle
#7
Luke Miller, Jason A Ferreira, Calvin Tucker
BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding...
March 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27697442/discontinuation-and-management-of-direct-acting-anticoagulants-for-emergency-procedures
#8
REVIEW
Jerrold H Levy
Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures...
November 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27697438/idarucizumab-and-factor-xa-reversal-agents-role-in-hospital-guidelines-and-protocols
#9
REVIEW
Menno V Huisman, John Fanikos
As expected with all antithrombotic agents, there is a risk of bleeding complications in patients receiving direct oral anticoagulants (DOACs) because of the DOAC itself, acute trauma, invasive procedures, or underlying comorbidities. For many bleeding events, a prudent course of action will be to withdraw the DOAC, then "wait and support" the patient, with the expectation that the bleeding event should resolve with time. Likewise, DOAC therapy may be interrupted ahead of a planned procedure, the stopping time being dependent on the agent involved and the patient's renal function...
November 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27659071/nonvitamin-k-antagonist-oral-anticoagulant-activity-challenges-in-measurement-and-reversal
#10
REVIEW
Karen S Brown, Hamim Zahir, Michael A Grosso, Hans J Lanz, Michele F Mercuri, Jerrold H Levy
BACKGROUND: Four nonvitamin K antagonist oral anticoagulants (NOACs) are approved for the prevention of stroke in patients with nonvalvular atrial fibrillation and for the treatment of venous thromboembolism. These include the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. Bleeding is a complication for all anticoagulants and concerns regarding bleeding risk and the suitability of effective reversal strategies may be a barrier to their prescription...
September 23, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27626268/-antidotes-to-novel-direct-oral-anticoagulants
#11
REVIEW
N G Khorev, A P Momot, V O Kon'kova
During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation)...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/27594818/novel-oral-anticoagulants-for-venous-thromboembolism-with-special-emphasis-on-risk-of-hemorrhagic-complications-and-reversal-agents
#12
Zaheer Ahmed, Seemeen Hassan, Gary A Salzman
Warfarin was the only oral anticoagulant available for the treatment of venous thromboembolism for about half a century until the recent approval of novel oral agents dabigatran, rivoraxaban and apixaban. This presents new classes of medications less cumbersome to use. They do not require frequent laboratory monitoring or have nurmerous drug interactions. On the other hand it also poses a challenge to the physicians deciding which agent to use in specific patient populations, how to predict the bleeding risk compared to warfarin and between the different novel agents and how to manage bleeding with relatively recent discovery of few potential antidotes...
April 2016: Current Drug Therapy
https://www.readbyqxmd.com/read/27569675/discontinuation-and-management-of-direct-acting-anticoagulants-for-emergency-procedures
#13
Jerrold H Levy
Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures...
November 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/27569673/idarucizumab-and-factor-xa-reversal-agents-role-in-hospital-guidelines-and-protocols
#14
Menno V Huisman, John Fanikos
As expected with all antithrombotic agents, there is a risk of bleeding complications in patients receiving direct oral anticoagulants (DOACs) because of the DOAC itself, acute trauma, invasive procedures, or underlying comorbidities. For many bleeding events, a prudent course of action will be to withdraw the DOAC, then "wait and support" the patient, with the expectation that the bleeding event should resolve with time. Likewise, DOAC therapy may be interrupted ahead of a planned procedure, the stopping time being dependent on the agent involved and the patient's renal function...
November 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/27558534/4-factor-prothrombin-complex-concentrate-pcc4-kcentra%C3%A2-protocol-reduces-blood-requirements-for-heart-transplantation-a-novel-protocol
#15
Jacqueline Pratt Cleary, Laura Hodge, Brittany Palmer, Christopher J Barreiro, Amanda Ingemi
BACKGROUND All patients with a ventricular assist device (VAD) awaiting heart transplantation are anticoagulated with warfarin to prevent thromboembolism. The use of 4 factor prothrombin complex concentrate (PCC4, Kcentra®) for anticoagulation reversal prior to surgery may include benefits such as quicker reversal, longer duration of action, and a reduction in total volume of blood products used compared to other reversal practices. The study objective is to evaluate benefits of using an anticoagulation reversal protocol featuring PCC4, over standard of care in heart transplant patients requiring anticoagulation...
August 25, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27522492/the-role-of-glycoprotein-iib-iiia-inhibitors-in-acute-coronary-syndromes-and-the-interference-with-anemia
#16
REVIEW
Paolo Emilio Puddu, Loredana Iannetta, Attilio Placanica, Domenico Cuturello, Michele Schiariti, Olivia Manfrini
The role played by glycoprotein (GP) IIb/IIIa inhibitors (GPI) has continuously evolved until the most recent Guidelines whereby they were stepped down from class I to class II recommendation for treating acute coronary syndromes (ACS). GPI compete with a wider use of ADP inhibitors and novel anticoagulant drugs although GPI use has greatly narrowed. However, GPI may still have a role. Several criteria were proposed to define post-PCI anemia which is strictly related to bleeding and transfusion. In ACS, it should be important to define anemia in comparative terms versus baseline levels: ≥ 15% of red blood cell decrease should be a practical cut-off value...
November 1, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27477871/idarucizumab-clinical-role-of-a-novel-reversal-agent-for-dabigatran
#17
REVIEW
Mohamed Teleb, Kevin Salire, Miraie Wardi, Haider Alkhateeb, Sarmad Said, Debabrata Mukherjee
Atrial fibrillation (AF), a common cardiac arrhythmia associated with increased risk of heart failure, thromboembolic phenomena and death, is a leading cause of hospitalization of adults. A major complication of AF is an increased risk of ischemic stroke leading to long-term disability and in severe cases, death. Historically, Coumadin has been the drug of choice for chronic anticoagulation and stroke prevention in AF patients however, given the need for constant monitoring and multiple drug interactions, newer anticoagulants have been developed...
2016: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/27470323/ciraparantag-safely-and-completely-reverses-the-anticoagulant-effects-of-low-molecular-weight-heparin
#18
Jack E Ansell, Bryan E Laulicht, Sasha H Bakhru, Maureane Hoffman, Solomon S Steiner, James C Costin
Major bleeding with low molecular weight heparin (LMWH) therapy occurs in up to 5% of patients and its anticoagulation is only partially reversed by protamine sulfate. We studied the ability of ciraparantag (PER977), a novel agent that reverses LMWH in preclinical studies, to reverse LMWH in healthy volunteers. METHODS: In this phase 1/2 trial, 4 cohorts of 10 healthy volunteers received escalating doses of ciraparantag (100 to 300mg) or placebo (8:2 ratio) approximately 4h after a single subcutaneous dose of enoxaparin, 1...
October 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27467511/allosteric-inhibition-of-factor-xiiia-non-saccharide-glycosaminoglycan-mimetics-but-not-glycosaminoglycans-exhibit-promising-inhibition-profile
#19
Rami A Al-Horani, Rajesh Karuturi, Michael Lee, Daniel K Afosah, Umesh R Desai
Factor XIIIa (FXIIIa) is a transglutaminase that catalyzes the last step in the coagulation process. Orthostery is the only approach that has been exploited to design FXIIIa inhibitors. Yet, allosteric inhibition of FXIIIa is a paradigm that may offer a key advantage of controlled inhibition over orthosteric inhibition. Such an approach is likely to lead to novel FXIIIa inhibitors that do not carry bleeding risks. We reasoned that targeting a collection of basic amino acid residues distant from FXIIIa's active site by using sulfated glycosaminoglycans (GAGs) or non-saccharide GAG mimetics (NSGMs) would lead to the discovery of the first allosteric FXIIIa inhibitors...
2016: PloS One
https://www.readbyqxmd.com/read/27465882/novel-oral-anticoagulant-management-issues-for-the-stroke-clinician
#20
REVIEW
Andrew Wassef, Ken Butcher
BACKGROUND: Four nonvitamin K antagonist oral anticoagulants (NOACs) are approved for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). AIMS: In this review, we assemble available evidence for the best management of ischemic and hemorrhagic stroke patients in the context of NOAC use. SUMMARY OF REVIEW: NOACs provide predictable anticoagulation with fixed dosages. The direct thrombin inhibitor dabigatran and direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban are all noninferior to warfarin for the prevention of ischemic stroke and systemic embolism and are associated with reduced incidence of intracranial hemorrhage...
October 2016: International Journal of Stroke: Official Journal of the International Stroke Society
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