Emergency reversal of antithrombotic treatment

Abstract

The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. In case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when a patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be reversed by various specific strategies. Heparin and heparin derivatives can be counteracted by protamine sulphate, whereas the anticoagulant effect of vitamin K antagonists may be neutralized by administration of vitamin K or prothrombin complex concentrates. The anti-hemostatic effect of aspirin and other anti-platelet strategies can be corrected by the administration of platelet concentrate or desmopressin, if needed. Recently, a new generation of anticoagulants with a greater specificity towards activated coagulation factors has been introduced and most of these agents are presently being evaluated in clinical studies. The new generation anticoagulants include specific inhibitors of factor IIa, factor Xa (including pentasaccharides) and agents that interfere with tissue factor activity. A limitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs, although in some cases the administration of recombinant factor VIIa may be an option.

Reversing Dabigatran in Life-Threatening Bleeding Occurring During Cardiac Ablation With Factor Eight Inhibitor Bypassing Activity

“…The proposed mechanism for this was that the presence of activated factor VII, prothrombin, and activated factor X-the major components of FEIBA-induces rapid thrombin generation and critical components of the prothrombinase complex. Unlike other anticoagulants, direct inhibition of thrombin may also impact not only the conversion of fibrinogen to fibrin, but processes such as the platelet activation and other functions mediated by the enzyme (20). In our case, the TT and dabigatran concentration using a chromogenic ecarin test, did not normalize after FEIBA administration.…”

“…The increase in the aPTT (34-59 s), ECT (33-69 s), thrombin time (TT) (>120 s), and ETP (2.9-7.5 min) after starting dabigatran was not reversed by the PCC4 (14). In an ex vivo analysis, FEIBA (20,40,80, and 160 U/kg equivalent) and a PCC4 PCC Kanokad (Laboratoire Français des Biotechnologies, Courtaboeuf, France) [12.5, 25, and 50 units/kg equivalent] demonstrated a dose-related correction in the ETP compared with rFVIIa (20, 60, and 120 mcg/kg equivalent), with FEIBA being the only agent to correct all thrombin generation times (17). Although in early stages of development, an antibody to dabigatran is being investigated (19).…”

Benefits and harms of 4-factor prothrombin complex concentrate for reversal of vitamin K antagonist associated bleeding: a systematic review and meta-analysis

“…Depending on the clinical situation this reversal need to be completed within several hours or immediate [9]. The most straightforward intervention to counteract the effect of VKA is the administration of vitamin K [1, 10, 11].…”

Emergency Reversal of Antiplatelet Agents in Patients Presenting with an Intracranial Hemorrhage: A Clinical Review

“…Furthermore, other agents for reversal of the aspirin effect have received basic investigation. Desmopressin seems capable of correcting aspirin-induced platelet dysfunction, although large clinical studies describing relevant outcome parameters have not been undertaken [46][47][48]. Altman, et al [49] treated healthy volunteers with aspirin and found that recombinant factor VIIa (rFVIIIa) combined with other agonists was able to reverse the anti-aggregating effect of aspirin.…”