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https://www.readbyqxmd.com/read/28581331/exploring-indications-for-the-use-of-direct-oral-anticoagulants-and-the-associated-risks-of-major-bleeding
#1
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/28509773/perioperative-management-of-antithrombotic-therapies
#2
Timur Yurttas, Patrick M Wanner, Miodrag Filipovic
PURPOSE OF REVIEW: Perioperative coagulation management is becoming increasingly frequent in the daily routine of the anesthesiologist and with the plethora of new substances on the market also increasingly complex. The perioperative setting poses unique challenges requiring an individualized evaluation and management of antithrombotic therapy. This review shall summarize the newest developments in this domain. RECENT FINDINGS: New data in patients with atrial fibrillation have led to a paradigm change in the perioperative management of antithrombotics...
August 2017: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/28386620/direct-oral-anticoagulants-doac-management-of-emergency-situations-rationale-and-design-of-the-radoa-registry
#3
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/28314985/the-role-of-new-oral-anticoagulants-in-orthopaedics-an-update-of-recent-evidence
#4
REVIEW
Dimitrios V Papadopoulos, Ioannis Kostas-Agnantis, Ioannis Gkiatas, Andreas G Tsantes, Panagiota Ziara, Anastasios V Korompilias
Rivaroxaban, dabigatran, apixaban and edoxaban are the four available new oral anticoagulants (NOAC) which are currently approved for venous thromboembolism prophylaxis after total hip and knee replacement. Large phase 3 and phase 4 studies comparing NOAC with low molecular weight heparins have shown similar results regarding the efficacy and safety of these two categories of anticoagulants. Management of bleeding complications is a matter of great significance. Three reversal agents have been developed: idarucizumab, andexanet alfa and ciraparantag...
March 17, 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#5
REVIEW
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/27895055/role-of-agents-for-reversing-the-effects-of-target-specific-oral-anticoagulants
#6
REVIEW
Tanya R Riley, Mary L Gauthier-Lewis, Chelsea K Sanchez, Janine S Douglas
PURPOSE: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents. Several treatment options for the management of life-threatening bleeding events associated with TSOAC use, such as fresh frozen plasma, prothrombin complex concentrates, and recombinant coagulation factor VIIa, have been used, with inconsistent results...
January 15, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27853809/single-dose-ciraparantag-safely-and-completely-reverses-anticoagulant-effects-of-edoxaban
#7
Jack E Ansell, Sasha H Bakhru, Bryan E Laulicht, Solomon S Steiner, Michael A Grosso, Karen Brown, Victor Dishy, Hans J Lanz, Michele F Mercuri, Robert J Noveck, James C Costin
Of the new direct oral anticoagulants, direct factor Xa inhibitors are limited by the absence of a proven reversal agent. We assessed the safety, tolerability and impact on anticoagulation reversal of ciraparantag (PER977) alone and following a 60 mg dose of the FXa inhibitor edoxaban. Escalating, single IV doses of ciraparantag were administered alone and following a 60 mg oral dose of edoxaban in a double-blind, placebo-controlled fashion to healthy subjects. Serial assessments of the pharmacokinetics and pharmacodynamic effects of ciraparantag were performed...
January 26, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27697443/preclinical-and-clinical-data-for-factor-xa-and-universal-reversal-agents
#8
REVIEW
Truman J Milling, Scott Kaatz
Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development...
November 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27697442/discontinuation-and-management-of-direct-acting-anticoagulants-for-emergency-procedures
#9
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
#10
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/27625113/measurement-and-reversal-of-the-direct-oral-anticoagulants
#11
REVIEW
Bethany T Samuelson, Adam Cuker
Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors...
January 2017: Blood Reviews
https://www.readbyqxmd.com/read/27575436/preclinical-and-clinical-data-for-factor-xa-and-universal-reversal-agents
#12
REVIEW
Truman J Milling, Scott Kaatz
Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development...
November 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/27569675/discontinuation-and-management-of-direct-acting-anticoagulants-for-emergency-procedures
#13
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 Medicine
https://www.readbyqxmd.com/read/27569673/idarucizumab-and-factor-xa-reversal-agents-role-in-hospital-guidelines-and-protocols
#14
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 Medicine
https://www.readbyqxmd.com/read/27548686/reversal-agents-for-direct-oral-anticoagulants-understanding-new-and-upcoming-options
#15
REVIEW
Kelly C Rogers, Melanie P Shelton, Shannon W Finks
Direct oral anticoagulants (DOACs), originally developed as an alternative for vitamin K antagonists, are shifting the landscape of antithrombotic therapy. DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban offer enhancements in safety, convenience, and efficacy compared with warfarin. However, as choices for oral anticoagulation therapy have increased, so has the need for effectual antidotes before urgent surgical procedures and for the reversal of serious adverse events caused by DOACs. To date, one antidote has been FDA approved in the United States for the reversal of dabigatran, and two antidotes are undergoing phase 2and 3clinical trials...
November 2016: Cardiology in Review
https://www.readbyqxmd.com/read/27544033/ciraparantag-for-enoxaparin-reversal-adding-to-the-evidence
#16
EDITORIAL
Jeffrey I Weitz, John W Eikelboom
No abstract text is available yet for this article.
October 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27541665/reversal-agents-for-direct-oral-anticoagulants-a-focused-review
#17
REVIEW
Boris Arbit, Marin Nishimura, Jonathan C Hsu
For several decades the vitamin K antagonist oral anticoagulants were the only outpatient therapy that existed to reduce the risk of stroke and thromboembolism. When the new direct oral anticoagulants were approved for use and addressed many of the issues associated with oral vitamin K antagonists, a new concern arose-the lack of rapid ability to reverse these agents. Physicians and patients were concerned that in cases of life-threatening bleeding or need for emergent surgery, an antidote to reverse the anticoagulation effect of these agents did not exist...
November 15, 2016: International Journal of Cardiology
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/27436881/management-of-bleeding-with-non-vitamin-k-antagonist-oral-anticoagulants-in-the-era-of-specific-reversal-agents
#19
REVIEW
Christian T Ruff, Robert P Giugliano, Elliott M Antman
Vitamin K antagonists are commonly used by clinicians to provide anticoagulation to patients who have or are at risk of having thrombotic events. In addition to familiarity with the dosing and monitoring of vitamin K antagonists, clinicians are accustomed to using vitamin K if there is a need to reverse the anticoagulant effect of vitamin K antagonists. There are now 4 new non-vitamin K antagonist oral anticoagulants (NOACs) that are attractive alternatives to vitamin K antagonists. Despite similar or lower rates of serious bleeding with NOACs in comparison with warfarin, there is a pressing need for strategies to manage bleeding when it does occur with NOACs and to reverse the pharmacological effect of these agents if needed...
July 19, 2016: Circulation
https://www.readbyqxmd.com/read/27215215/reversal-of-newer-direct-oral-anticoagulant-drugs-doacs
#20
Saad S Hussain, Alan H Tyroch, Debabrata Mukherjee
Anticoagulation therapy is indicated for management of various clinical conditions to prevent adverse events and introduction of direct oral anticoagulants (DOACs) has ushered in a new era in anticoagulation therapy. Major advantages of DOACS include fewer drug interactions and that they do not need periodic monitoring. Several patients who were not on anticoagulation before due to older age, polypharmacy/drug interaction concerns, and logistics of periodic monitoring are now on anticoagulation with DOACs. Despite their many advantages, a challenge while prescribing DOACs is very limited availability of specific reversal agents and lack of understanding or guidance about the treatment strategy in case of major life threatening bleeding or need for urgent surgery...
2017: Cardiovascular & Hematological Agents in Medicinal Chemistry
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