What is Kcentra (prothrombin complex concentrate) used for?

Kcentra (Prothrombin Complex Concentrate) Usage

Kcentra (4-factor prothrombin complex concentrate or 4F-PCC) is primarily used for urgent reversal of vitamin K antagonist (warfarin) anticoagulation in adult patients with acute major bleeding or need for urgent surgery or invasive procedures. 1

Primary Indications

• FDA-approved use:
  • Urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA) therapy in adult patients with:
    • Acute major bleeding
    • Need for urgent surgery or invasive procedures

Mechanism of Action

Kcentra contains concentrated forms of the vitamin K-dependent coagulation factors:

• Factor II (prothrombin)
• Factor VII
• Factor IX
• Factor X
• Small amounts of protein C and S
• Small amounts of heparin

Unlike fresh frozen plasma (FFP), Kcentra:

• Does not require blood type matching
• Can be administered more rapidly (10-30 minutes)
• Requires significantly less volume
• Does not require thawing 1

Dosing

• Standard starting dose: 25 IU/kg based on pre-treatment INR 1
• INR should be checked 30 minutes after administration to assess reversal
• Must be administered with 5-10 mg of intravenous vitamin K due to the short half-life of factor VII (6 hours) 1

Clinical Efficacy

• Rapidly reverses warfarin anticoagulation within 10-30 minutes 1
• Studies show mean INR decreases from elevated levels (as high as 5.7) to normal range (1.5) after administration 2
• Reversal effect lasts more than 48 hours after administration 2

Off-Label Uses

While not FDA-approved for these indications, Kcentra is sometimes used for:

• Reversal of direct oral anticoagulants (DOACs) like rivaroxaban (Xarelto) and apixaban (Eliquis) in emergency situations 1, 3
• Reversal of anticoagulation with direct thrombin inhibitors (e.g., dabigatran) 1
• Management of major hemorrhage not related to vitamin K antagonists 1
• Treatment of non-life-threatening bleeding in patients who cannot tolerate large volumes of FFP 1

Important Considerations

Efficacy Limitations with DOACs

• Evidence for reversal of factor Xa inhibitors (rivaroxaban, apixaban) is limited and conflicting 1, 3
• PCCs do not truly "reverse" Xa inhibitors but rather provide coagulation factors that may overcome the anticoagulant effect 3
• Laboratory studies show that PCCs like Kcentra do not fully reverse anti-Xa activity 3

Safety Concerns

• Thrombotic risk: Kcentra administration carries increased risks of both venous and arterial thrombosis 3, 4
• Pharmacovigilance data shows thromboembolic events occur in approximately 1 per 9,963 standard infusions 4
• The risk of thrombotic complications must be weighed against the need for rapid correction of coagulopathy 3
• Hypersensitivity reactions occur in approximately 1 per 64,485 standard infusions 4

Advantages Over Fresh Frozen Plasma

• More rapid reversal of anticoagulation
• No need for blood type matching
• Smaller volume administration
• No risk of transfusion-related acute lung injury
• No thawing required
• Potentially lower risk of volume overload 1, 5

Clinical Decision-Making

When considering Kcentra for anticoagulation reversal:

1. Confirm the anticoagulant in use (most effective for warfarin)
2. Assess bleeding severity and location (especially critical sites like intracranial)
3. Measure baseline coagulation parameters (INR)
4. Consider thrombotic risk factors in the patient
5. Administer with vitamin K for sustained reversal
6. Monitor post-administration INR and clinical response

For non-warfarin anticoagulants, specific reversal agents (when available) may be preferable to Kcentra 3.