title: Bleeding and antidotes in new oral anticoagulants.
abstract: In the past decade, several new oral anticoagulants (NOACs) have been studied and approved for the prophylaxis and treatment of arterial and venous thromboembolism. These agents were shown to be as effective as or better than warfarin and resulted in comparable or lower bleeding rates than warfarin. Specific antidotes for the reversal of the anticoagulant effect of these drugs, such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or recombinant Xa-analog in the case of factor Xa inhibitors, are still being investigated in early clinical trials. In certain situations, as in case of emergency surgery or life-threatening major bleeding, a rapid reversal strategy is needed. Several non-specific prohemostatic agents or coagulation factor concentrates have been suggested as potential candidates for the reversal of NOACs, but the evidence supporting these agents was mainly derived from small animal studies, or is based on partial or complete correction of laboratory parameters in healthy volunteers treated with these agents. Activated prothrombin complex concentrate seems promising for the reversal of dabigatran, while non-activated prothrombin complex concentrates have potential for the reversal of anti-factor Xa. The risk of thromboembolic complications requires careful evaluation. In this article, the evidence- or the lack of it - supporting the use of the different prohemostatic agents for the management of bleeding and for reversal of the different classes of NOACs is discussed.
authors: Hematology Center, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden.
authors: Ammar
authors: A
authors: Majeed
authors: Sam
authors: S
authors: Schulman
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D000069604:Dabigatran; D004334:Drug Administration Schedule; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000009:adverse effects; D011516:Prothrombin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000069552:Rivaroxaban; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects; D013923:Thromboembolism / Q000188:drug therapy* / Q000473:pathology; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D001779:Blood Coagulation Factors; D006490:Hemostatics; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; D013876:Thiophenes; D015091:beta-Alanine; C522181:apixaban; D011516:Prothrombin; D000069552:Rivaroxaban; D000069604:Dabigatran; C552171:edoxaban
keywords: apixaban; bleeding; dabigatran; edoxaban; reversal; rivaroxaban