When to draw prothrombin time (PT) after administration of Kcentra (prothrombin complex concentrate)?

From the Guidelines

Prothrombin time (PT) should be drawn approximately 15-30 minutes after completing Kcentra administration to assess the initial response to therapy. This recommendation is based on the pharmacokinetics of Kcentra, a 4-factor prothrombin complex concentrate, which has an onset of effect within 5 to 15 minutes and a duration of effect of 12 to 24 hours 1. The timing of PT measurement is crucial to confirm adequate reversal of anticoagulation, especially in patients with life-threatening bleeding or those requiring urgent procedures.

• Key factors to consider when determining the timing of PT measurement include:
  • The clinical situation and the goal PT/INR value
  • The presence of active bleeding
  • The maintenance dose of the vitamin K antagonist (VKA)
  • The magnitude of INR elevation
  • The desired range into which to reduce the INR Additional PT measurements are typically recommended at 6 hours post-administration and then 24 hours after Kcentra to monitor the durability of coagulation correction, as the half-life of the various clotting factors (II, VII, IX, X) is approximately 24-48 hours 1.
• The use of Kcentra is typically reserved for urgent reversal of vitamin K antagonists like warfarin, and the initial post-administration PT helps guide whether additional doses might be needed, particularly in patients with ongoing bleeding or those requiring urgent procedures. The American College of Cardiology/American Heart Association joint committee on clinical practice guidelines recommends a 10-mg intravenous dose of vitamin K for life-threatening bleeding 1.

From the FDA Drug Label

The median INR was above 3. 0 prior to the infusion and dropped to a median value of 1.20 by the 30 minute time point after start of KCENTRA infusion. The proportion of subjects with a decrease in INR to ≤ 1.3 at 30 minutes after the end of infusion of KCENTRA was 55.2%. Of the 17 evaluable subjects receiving KCENTRA for acute bleeding, 16 subjects (94%) experienced a decrease in INR to ≤ 1.3 within 30 minutes after the end of the KCENTRA infusion.

The patient should be drawn 30 minutes after the start of KCENTRA infusion or within 30 minutes after the end of the infusion, as the INR is expected to decrease to ≤ 1.3 at this time point 2.

From the Research

Timing of PT Draw after Kcentra Administration

• The studies do not provide a specific timeframe for drawing PT after Kcentra administration 3, 4, 5, 6, 7.
• However, the studies suggest that Kcentra is effective in reversing elevated INRs in patients with warfarin-induced coagulopathy, with results lasting more than 48 hours after administration 3.
• One study found that the mean INR decreased from 5.7 to 1.5 after 4F-PCC administration, and remained at 1.4 after 48 hours 3.
• Another study found that 4F-PCC reduced the time to reach INR correction compared to fresh frozen plasma or no treatment 4.
• The studies also suggest that Kcentra is safe and effective in normalizing INR in patients with warfarin-associated bleeding 5, 6, 7.

Factors Affecting PT Draw after Kcentra Administration

• The baseline INR value may affect the timing of PT draw after Kcentra administration, as patients with higher baseline INR values may require longer to achieve INR correction 3, 4.
• The dose of Kcentra administered may also affect the timing of PT draw, as higher doses may result in more rapid INR correction 5, 6.
• The presence of bleeding complications may also affect the timing of PT draw, as patients with active bleeding may require more frequent monitoring of INR 3, 4.