Prothrombin complex concentrate(Sanquin Blood Supply Foundation)

Prothrombin complex concentrate (PCC) is used to boost thrombin potential, support clot formation, and aid in the treatment and prophylaxis of bleeding. The two main forms of PCC are three-factor (3 F-PCC; comprising coagulation factors II, IX, and X) and four-factor (4F-PCC; factors II, VII, IX, X), which contain 25 times the clotting factors found in human plasma. This narrative review summarizes published efficacy and safety data on one 4F-PCC (Octaplex/Balfaxar, Octapharma) within its recognized uses and explores potential applications across different clinical contexts. Clinically available for > 20 years, Octaplex/Balfaxar is supplied as a freeze-dried powder for reconstitution and intravenous infusion. This 4F-PCC contains non-activated forms of coagulation factors as well as anticoagulant proteins C and S, potentially affording a balanced hemostatic effect and mitigating thrombosis risk. Production involves two virus inactivation/removal steps: solvent/detergent treatment and nanofiltration. 4F-PCC is approved for acquired deficiency of vitamin K-dependent clotting factors, such as those induced by vitamin K antagonists (VKAs, e.g., warfarin), and for congenital deficiency of factors II and X. Five published trials in 444 adult patients demonstrated the efficacy of 4F-PCC in VKA reversal, reducing the international normalized ratio (INR) with only two potentially treatment-related thrombotic events reported. While 4F-PCC dosing is currently indicated to be INR-guided, emerging evidence supports fixed dosing as an alternative to conventional weight-based dosing for VKA reversal. Recent guidelines support 4 F-PCC use for direct oral anticoagulant-associated bleeding, cardiac surgery and trauma/emergencies. Ongoing studies will further clarify the efficacy and safety of 4 F-PCC beyond its approved indications.

To provide evidence for the use of prothrombin complex concentrate (PCC) as a potential hemostatic treatment for trauma-induced coagulopathy with and without anticoagulants.

PCC is effective in enhancing thrombin generation and achieving hemostasis in traumatized patients under anticoagulants. For vitamin K antagonist (VKA) reversal, it shows superior efficacy over fresh frozen plasma, achieving rapid normalization of the international normalized ratio normalization and reduced transfusion needs. In direct oral anticoagulant (DOAC)-associated bleeding, PCC offers an alternative when specific antidotes are unavailable. However, evidence from randomized trials in the field of trauma and coagulopathy is limited, and the results have shown conflicting outcomes in terms of mortality reduction. Further, following PCC application, thromboembolic risks remain a particular concern. Monitoring tools such as thrombin generation assays and point-of-care tests show promise but are not universally available.

PCC is a valuable option for managing coagulopathy in specific settings, especially VKA and DOAC reversal. Based on current evidence, we caution against the use of PCC as a versatile hemostatic agent suitable for indications involving multiple clotting factor deficiencies for uncontrolled coagulopathic bleeding in trauma or other clinical settings outside anticoagulation reversal. The risk vs. benefit profile should be carefully examined, similar to any other agent.