What is 4 factor Prothrombin Complex Concentrate (4F-PCC)?

4-Factor Prothrombin Complex Concentrate (4F-PCC)

4F-PCC is a pathogen-reduced, lyophilized concentrate containing therapeutic amounts of coagulation factors II, VII, IX, and X, as well as proteins C and S, derived from pooled human plasma, primarily used for rapid reversal of vitamin K antagonist anticoagulation in patients with major bleeding or requiring urgent procedures. 1, 2

Composition and Characteristics

• 4F-PCC contains approximately 25 times the concentration of vitamin K-dependent factors compared to plasma per unit volume, allowing for more effective and rapid coagulation correction 1
• The product is stored as a lyophilized powder at room temperature, enabling quick reconstitution and administration in emergency situations 1
• 4F-PCC undergoes pathogen reduction and inactivation processes during manufacturing, making it free of viral contaminants 1

Clinical Applications

• Primary FDA-approved indication: Urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA) therapy in patients with acute major bleeding or need for urgent surgery/invasive procedures 1, 3
• Off-label uses have expanded to include direct oral anticoagulant reversal, trauma-induced coagulopathy, post-cardiopulmonary bypass bleeding, and coagulopathy in liver failure 2, 3
• Recommended dosing for VKA reversal is weight-based and INR-dependent:
  • 25 U/kg for INR 2 to <4
  • 35 U/kg for INR 4 to 6
  • 50 U/kg for INR >6
  • Maximum dose: 5,000 units 1

Advantages Over Fresh Frozen Plasma (FFP)

• No requirement for ABO blood group compatibility testing, reducing preparation time 1
• Rapid reconstitution and administration (20-30 minutes) compared to hours for FFP 1
• Significantly smaller volume required, reducing risk of volume overload in vulnerable patients 1
• More effective INR correction, with ability to normalize INR to ≤1.4 in nearly 100% of patients within 30 minutes 1, 4
• Associated with reduced requirements for packed red blood cell transfusions 1

Clinical Efficacy

• For intracranial hemorrhage in warfarin patients, 4F-PCC demonstrates faster INR reversal and decreased hemorrhage progression compared to plasma 1
• Fixed-dose protocols (e.g., 1500 units) have shown efficacy in achieving target INR ≤1.5 in approximately 75% of patients requiring urgent warfarin reversal, with 100% achieving INR ≤2.0 5
• Meta-analysis suggests potential mortality benefit with 4F-PCC versus no treatment (OR 0.41) or FFP (OR 0.64), though not statistically significant 4

Safety Profile

• Main safety concerns include risk of thromboembolic events, allergic reactions, and heparin-induced thrombocytopenia 1
• Pharmacovigilance data shows thromboembolic events occur in approximately 1 per 9,963 standard infusions, with most cases having pre-existing risk factors for thrombosis 6
• Hypersensitivity reactions are rare, occurring in approximately 1 per 64,485 standard infusions 6
• No confirmed cases of viral transmission related to 4F-PCC use have been reported 6

Important Clinical Considerations

• 4F-PCC should be administered as soon as possible after diagnosis of major bleeding in anticoagulated patients to improve outcomes 1
• When used for VKA reversal, 4F-PCC should always be co-administered with intravenous vitamin K to prevent rebound increases in INR 1
• Patients should be monitored for signs of thromboembolic complications after administration 1
• Lower doses than recommended in product labeling are frequently used in clinical practice (25% of cases in one study), though optimal dosing strategies for various indications remain under investigation 3