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

What is 4-Factor Prothrombin Complex Concentrate (PCC)

4-factor prothrombin complex concentrate (4F-PCC) is a concentrated plasma-derived product containing therapeutic amounts of four vitamin K-dependent coagulation factors (II, VII, IX, and X) along with proteins C and S, designed primarily for rapid reversal of vitamin K antagonist anticoagulation. 1

Composition and Properties

4F-PCC differs from 3-factor PCC in its complete factor profile:

• 4F-PCC contains: Factors II, VII, IX, X, and proteins C and S
• 3F-PCC contains: Factors II, IX, X with negligible Factor VII 1

Key advantages of 4F-PCC over fresh frozen plasma (FFP):

• Rapid administration: Can be reconstituted and infused in 15-30 minutes 1
• No blood type matching required: No ABO compatibility testing needed 1
• Concentrated volume: Contains approximately 25 times the concentration of coagulation factors compared to plasma (25 U/mL vs 1 U/mL) 1
• Room temperature storage: Stored as lyophilized powder at room temperature 1
• Pathogen reduction: Undergoes viral inactivation processes 1
• No volume overload risk: Smaller volume compared to FFP 1

Clinical Applications

FDA-Approved Indication

• Urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA) therapy in adult patients with acute major bleeding 1

Common Off-Label Uses

• Reversal of direct oral anticoagulants (DOACs), particularly factor Xa inhibitors when specific reversal agents are unavailable 1
• Management of trauma-induced coagulopathy 2, 3
• Treatment of bleeding in cardiac surgery 4
• Management of coagulopathy in liver failure 2

Dosing

For VKA reversal, dosing is based on pre-treatment INR and body weight:

• INR 2 to <4: 25 U/kg
• INR 4-6: 35 U/kg
• INR >6: 50 U/kg
• Maximum dose: 5,000 units (capped at 100 kg body weight) 1

For non-VKA indications, common dosing strategies include:

• Initial bolus of 25 IU/kg for massive bleeding with coagulopathy
• Consider lower initial dose (12.5 IU/kg) in patients with high thromboembolic risk, such as cardiac surgery patients 4

Efficacy and Safety

Efficacy

• Rapidly normalizes INR within 1 hour of administration 5
• More effective than FFP in correcting coagulopathy 1, 5
• Meta-analyses show approximately 80% hemostatic efficacy in DOAC-related bleeding 1

Safety Considerations

• Thromboembolic events: Risk appears relatively low (0-4%) but remains a concern 1, 5
• Should be used cautiously in patients with history of thromboembolism
• For VKA reversal, should always be administered with vitamin K to prevent rebound coagulopathy 1

Clinical Pearls

• When reversing VKA-associated bleeding, vitamin K should always be administered alongside 4F-PCC to restore endogenous production of vitamin K-dependent factors 1
• 4F-PCC is preferred over FFP for urgent VKA reversal according to multiple guidelines 1
• For intracranial hemorrhage in anticoagulated patients, rapid reversal with 4F-PCC within 4 hours of admission is associated with reduced mortality 1
• Fixed-dose strategies (e.g., 2000 IU) may be as effective as weight-based dosing for DOAC reversal while using less product 1

4F-PCC represents a significant advancement in the management of anticoagulation-associated bleeding, offering rapid and effective reversal with logistical advantages over traditional plasma transfusion.