4-Factor Prothrombin Complex Concentrate (PCC) Components
4-factor PCC contains therapeutic amounts of coagulation factors II, VII, IX, and X, as well as proteins C and S, derived from pooled human plasma. 1
Composition Details
- 4-factor PCCs contain all four vitamin K-dependent coagulation factors: II (prothrombin), VII, IX, and X 2
- These products are categorized as "4-factor" specifically because they include factor VII, which distinguishes them from 3-factor PCCs (containing only factors II, IX, and X) 2
- Most 4F-PCCs also contain anticoagulant proteins such as protein C, protein S, and sometimes protein Z or antithrombin 1, 2
- Many formulations also contain small amounts of heparin to reduce thrombotic risk 2
- Per unit volume, 4F-PCCs contain approximately 25 times the concentration of vitamin K-dependent factors compared to plasma 1
Product Characteristics
- 4F-PCCs are stored as lyophilized powders at room temperature, allowing for rapid reconstitution in emergency situations 1, 3
- They undergo pathogen reduction and inactivation processes during manufacturing to eliminate viral contaminants 1
- The products do not require ABO blood group compatibility testing or thawing, unlike fresh frozen plasma 2, 1
- 4F-PCCs can be administered rapidly (20-30 minutes) compared to hours for fresh frozen plasma 2, 1
Clinical Considerations
- Dosing of 4F-PCCs is typically based on factor IX content, with most products having approximately equivalent factor IX and X activity 2
- The half-lives of the contained factors differ significantly: factor VII (6 hours), factor IX (20 hours), factor X (30 hours), and factor II (60 hours) 2, 4
- This difference in half-lives can lead to accumulation of factors II and X with repeated dosing, potentially increasing thrombotic risk 2
- The main safety concerns with 4F-PCCs include risk of thromboembolic events, allergic reactions, and heparin-induced thrombocytopenia 1
Product Variability
- Commercial 4F-PCC products may differ in their exact composition of coagulation factors and inhibitors, presence of heparin and antithrombin, and purity 2
- There may also be variability between product batches of the same brand 2
- This variability can be particularly important for patients requiring frequent infusions 2
Clinical Applications
- Primary approved indication is for urgent reversal of vitamin K antagonist therapy in patients with major bleeding or requiring emergency surgery 1, 5
- Increasingly used off-label for management of trauma-induced coagulopathy and perioperative bleeding 2, 3
- When used for VKA reversal, 4F-PCC should be co-administered with intravenous vitamin K to prevent rebound increases in INR 1