Education Blog for Healthcare Professionals

Reversing Warfarin for Urgent Surgeries – Extended FDA Approval of Kcentra

Stephan Moll, MD writes… The FDA approved today (Dec 13th, 2013) the use of the drug Kcentra® for urgent warfarin reversal in patients who need an urgent surgical procedure.  This extends the indications for use of this drug – it had been approved by the FDA in April 2013 to treat major bleeding on warfarin [ref 1].

The drug is derived from pooled plasma from healthy blood donors and contains the coagulation factors that are low in warfarin-treated patients, i.e. factors II, VII, IX, and X.  It is also referred to as a 4-factor concentrate, or non-activated Prothrombin Complex Concentrate (PCC).  The study that lead to approval today for the additional indication was presented as an abstract at the American Society of Hematology meeting last week [ref 2].  It has not been published yet in the peer-reviewed literature.

 

The Study that Lead to Today’s Approval [ref 2]

Methods:  Patients requiring rapid reversal of warfarin and other vitamin K antagonists prior to an urgent surgical or invasive procedure were randomized to receive a single dose of either Kcentra® or plasma (fresh frozen plasma, FFP).  All patients were to receive vitamin K as early as possible.  The primary endpoints were (a) effective peri-operative hemostasis  and (b) rapid INR reduction (≤1.3 at 0.5 h after end of infusion).

Results:  168 patients were included (Kcentra® n=87; FFP n=81).  Effective hemostasis was achieved in 89.7% of patients in the Kcentra® group versus 75.3% in the FFP group, demonstrating superiority of Kcentra® over plasma (difference 14.3% [95%CI 2.8;25.8]).  Rapid INR reduction was achieved in 55.2% of patients in the Kcentra® group versus 9.9% in the FFP group, demonstrating superiority of Kcentra® over FFP(difference 45.3% [95%CI 31.9;56.4]).  Side effects were similar between treatment groups. Significantly fewer fluid overload events occurred with Kcentra® than with FFP.

Conclusions:  Kcentra was superior to FFP for hemostatic efficacy and for rapid INR reduction, with a favorable safety profile.

 

Personal Comments

  • When urgent reversal of warfarin anticoagulation prior to urgent surgery is needed, vitamin K together with 4 factor PCC (Kcentra®) are indicated.
  • Vitamin K together with 4 factor PCC (Kcentra®) are also indicated in the case of major bleeding on warfarin.
  • However, as recently published in the ASH Choosing Wisely®) campaign and discussed on Clot Connect (link here), FFP and PCC should not be routinely given to patients on warfarin who have elevated INRs but are not bleeding.

 

References

  1. Sarode R et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding. A randomized, plasma-controlled, phase IIIb study. Circulation 2013;128:1234-1243.
  2. Refaai MA et al.  Randomized Phase IIIb Study Of Rapid Vitamin K Antagonist Reversal In Patients Requiring An Urgent Surgical Procedure: Four-Factor Prothrombin Complex Concentrate Is Superior To Plasma. ASH annual meeting, Dec 6-10, 2013 (abstract #3588).

Disclosure:  I have been a consultant for CSL Behring, the company making Kcentra®.

Last updated: Dec 13th, 2013

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