ICH . 20 A modified recombinant FXa decoy molecule , andexanet alfa , is in late-phase testing as a reversal agent for factor Xa inhibitors , but is not yet clinically available . 21 Therefore , there is currently an unmet need for effective reversal agents for this class of direct-acting anticoagulants . A Phase II trial testing the antidote effects of 4F-PCC on dabigatran , a direct thrombin inhibitor , is currently ongoing . Data from a Phase II trial of anticoagulated volunteers given punch biopsies investigating reversal of the anticoagulation effects of edoxaban , an inhibitor of factor Xa , showed that administration of 4F-PCC at the highest dose tested resulted in complete reversal of the anticoagulant ’ s effects on bleeding duration and volume as well as endogenous thrombin potential , with a favourable safety profile . 22 In a Phase I trial , 4F-PCC reversed the anticoagulant effects of apixaban , also a factor Xa inhibitor , increasing peak thrombin generation and endogenous thrombin potential , and decreasing lag time and time to peak thrombin generation 23 ( Table 1 ).
Owing to its advantages over plasma , 4F-PCC is recommended for the urgent reversal of VKAs according to the treatment guidelines issued by the American College of Chest Physicians , 7 the British Society of Haematology , 24 and the European Task Force for Advanced Bleeding Care in Trauma . 25 Future studies will further refine its use in the clinic and elucidate its potential role in the reversal of specific NOACs .
Conclusions In summary , 4F-PPC is the preferred blood coagulation factor replacement product in the emergency setting . The ability to promptly reverse anticoagulantrelated bleeding is crucial for clinicians , who need to weigh the risks and benefits of anticoagulation therapy for extended periods of time in their practices , away from the ideal in the controlled setting of clinical trials . l
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