What is the onset of action of Kcentra (Prothrombin Complex Concentrate) for urgent warfarin reversal?

From the Guidelines

Kcentra (Prothrombin Complex Concentrate) has a rapid onset of action for urgent warfarin reversal, typically beginning within 10-30 minutes after administration. This is significantly faster than fresh frozen plasma, which can take several hours to reverse anticoagulation. Kcentra works by immediately replacing the vitamin K-dependent clotting factors II, VII, IX, and X that are inhibited by warfarin, allowing for rapid restoration of hemostasis in patients with serious bleeding or those requiring urgent surgical procedures. The full effect is usually achieved within 30 minutes of administration, with INR correction often observed within 10-15 minutes.

Key Points

• The dose of Kcentra is based on the patient's pre-treatment INR and body weight, typically ranging from 25-50 units/kg 1.
• For optimal results, Kcentra should be administered alongside vitamin K (typically 5-10 mg intravenously), as Kcentra provides immediate but temporary correction while vitamin K enables the body to resume its own production of clotting factors for sustained reversal 1.
• The use of 4-factor prothrombin complex concentrates (4F-PCCs) like Kcentra is recommended for urgent warfarin reversal, with a dosing regimen of 25-50 IU/kg 1.
• The optimal dosing regimen of 4F-PCCs is uncertain for DOAC reversal, but a meta-analysis found no significant differences in hemostatic effectiveness, thromboembolic events, or mortality rates between fixed and weight-based dosing strategies 1.
• Kcentra is the preferred agent for life-threatening bleeding in warfarin-treated patients when immediate reversal is necessary, due to its rapid onset of action and effectiveness in restoring hemostasis 1.

From the Research

Onset of Action of Kcentra

• The onset of action of Kcentra (Prothrombin Complex Concentrate) for urgent warfarin reversal is not explicitly stated in the provided studies.
• However, according to the study 2, prothrombin complex concentrates (PCCs) can achieve reversal of anticoagulation within a shorter time frame compared to fresh frozen plasma (FFP).
• The study 3 reports that Prothrombinex-VF, a three-factor prothrombin complex concentrate, can achieve complete or partial reversal of warfarin anticoagulation within 30 minutes of infusion.
• Another study 4 found that the addition of PCC to standard approaches for warfarin reversal resulted in a more rapid correction of the international normalized ratio (INR) in injured patients, with a mean time to achieve an INR of 1.5 or less of 16:59 hours in the PCC group.

Time to INR Correction

• The study 5 reports that PCC use resulted in a shorter time to INR correction, with a mean difference of -6.50 hours compared to FFP.
• The study 6 found that a fixed-dose 4PCC regimen of 2000 units was as effective as standard-dose 4PCC for INR reversal among patients with intracranial hemorrhage, with no difference in the ability to achieve a target INR of ≤1.4.
• The study 4 reports that the mean time to achieve an INR of 1.5 or less was 16:59 hours in the PCC group, compared to 30:03 hours in the no PCC group.

Efficacy and Safety

• The study 5 found that PCC use was associated with a significant reduction in all-cause mortality compared to FFP, and a higher proportion of patients receiving PCC achieved haemostasis.
• The study 3 reports that Prothrombinex-VF was effective and safe when used alone to reverse warfarin anticoagulation, with no adverse effects attributed to the treatment.
• The study 6 found that a fixed-dose 4PCC regimen was as effective as standard-dose 4PCC for INR reversal, with no difference in the ability to achieve a target INR of ≤1.4.