Clinical Relevance of Preclinical and Clinical Studies of Four-Factor Prothrombin Complex Concentrate for Treatment of Bleeding Related to Direct Oral Anticoagulants

Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of venous thromboembolism and stroke. When emergency reversal of DOAC-related anticoagulation is required, specific DOAC reversal agents are recommended, including idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. However, specific reversal agents are not always available, andexanet alfa has not been approved for urgent surgery, and clinicians need to know the patient's anticoagulant medication before administering these treatments. Four-factor prothrombin complex concentrates (4F-PCCs) are recognized as nonspecific, alternative hemostatic agents for treatment of DOAC-related bleeding. Evidence from preclinical and clinical studies shows that they may reduce the anticoagulant effects of DOACs and may help control DOAC-related bleeding. However, randomized controlled trials are lacking, and most data are from retrospective or single-arm prospective studies in bleeding associated with activated factor X inhibitors. There are no clinical data showing the efficacy of 4F-PCC for the treatment of bleeding in dabigatran-treated patients. This review focuses on the current evidence of 4F-PCC use in controlling bleeding associated with DOACs and provides an expert opinion on the relevance of these data for clinical practice. The current treatment landscape, unmet needs, and future directions are also discussed.

Automated summary

Direct oral anticoagulants (DOACs) are commonly used for preventing and treating venous thromboembolism and stroke. In cases where emergency reversal of DOAC-related anticoagulation is needed, specific DOAC reversal agents such as idarucizumab and andexanet alfa are recommended. However, these specific reversal agents may not always be available, and the use of four-factor prothrombin complex concentrates (4F-PCCs) as alternative hemostatic agents for controlling DOAC-related bleeding is being explored. This review discusses the current evidence and expert opinion on the use of 4F-PCCs in clinical practice.