Twenty years of the four-factor prothrombin complex concentrate Octaplex/Balfaxar: A narrative review

Keyvan Karkouti; Michelle Gareis; Chenxi Li; Hubert Brandstätter; Alexander Pichotta; Trupti Mehta Shah; Joshua N Goldstein

doi:10.1016/j.transci.2025.104115

Twenty years of the four-factor prothrombin complex concentrate Octaplex/Balfaxar: A narrative review

Transfus Apher Sci. 2025 Mar 30;64(3):104115. doi: 10.1016/j.transci.2025.104115. Online ahead of print.

Authors

Keyvan Karkouti¹, Michelle Gareis², Chenxi Li³, Hubert Brandstätter⁴, Alexander Pichotta⁵, Trupti Mehta Shah⁶, Joshua N Goldstein⁷

Affiliations

¹ Department of Anesthesia and Pain Management, University Health Network, Sinai Health System, Women's College Hospital, Toronto, Ontario, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Keyvan.Karkouti@uhn.ca.
² Octapharma Pharmazeutika Produktionsgesellschaft mbH, Vienna, Austria. Electronic address: michelle.gareis@octapharma.com.
³ Octapharma AG, Lachen, Switzerland. Electronic address: chenxi.li@octapharma.com.
⁴ Octapharma Pharmazeutika Produktionsgesellschaft mbH, Vienna, Austria. Electronic address: hubert.brandstaetter@octapharma.com.
⁵ Octapharma Biopharmaceuticals GmbH, Frankfurt, Germany. Electronic address: alexander.pichotta@octapharma.com.
⁶ Octapharma USA, Paramus, NJ, USA. Electronic address: Trupti.Mehta@octapharma.com.
⁷ Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: JGOLDSTEIN@mgh.harvard.edu.

PMID: 40188746
DOI: 10.1016/j.transci.2025.104115

Abstract

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.

Keywords: Anticoagulation reversal; Blood coagulation factors; Critical care; Factor Xa inhibitors; Hemorrhage; Hemostasis; Prothrombin complex concentrates; Surgery; Vitamin K deficiency bleeding.

Publication types

Review