DENVER – A four-factor prothrombin complex concentrate bettered plasma for urgent reversal of warfarin and other vitamin K antagonists in patients experiencing major bleeding.
Marketed as Beriplex, the product had a higher rate of INR reversal than did plasma at 30 minutes after the start of infusion, based on results from a phase IIIb prospective, multicenter, randomized clinical trial.
Dr. Joshua N. Goldstein
The prothrombin complex concentrate (PCC) also proved more successful than plasma at early replacement of depleted coagulation factors and was noninferior to plasma in terms of blinded investigator–rated hemostatic efficacy in the first 24 hours, Dr. Joshua N. Goldstein said at the annual meeting of the American College of Emergency Physicians.
The study included 202 adults on warfarin or another vitamin K antagonist who presented with acute major bleeding. The objectives were to correct their INR as quickly as possible and thereby reduce their blood loss. Participants were randomized to INR- and weight-based dosing of the PCC or to plasma on top of background vitamin K given by slow intravenous infusion in all cases.
Thirty minutes after the start of the infusion, the mean INR was significantly lower in patients on the PCC than in those given plasma. The higher the baseline INR, the greater the benefit of the PCC. For example, in 58 patients with a baseline INR above 6, the mean INR dropped from 10.6 preinfusion to 1.5 at 30 minutes in the PCC group and to 3.7 in the plasma recipients, reported Dr. Goldstein of the University of Rochester (N.Y.).
In 44 patients with a baseline INR of 4-6, the INR fell from a mean of 4.6 preinfusion to 1.4 at 30 minutes in the PCC group and to 3.2 in patients on plasma. And in patients with a baseline INR of 2 to less than 4, mean INR fell from 2.9 preinfusion to 1.6 in the PCC group and to 2.2 in the plasma recipients.
One hour after the start of infusion, roughly 70% of PCC recipients had corrected their INR as defined by an INR of 1.3 or less, compared with less than 5% of plasma recipients.
Median factor levels were below 50% at baseline. Levels increased significantly more within 30 minutes of starting PCC infusion than with plasma. This wasn’t particularly surprising, since the PCC contains factors II, VII, IX, and X, along with proteins C and S, Dr. Goldstein observed.
Blinded investigators rated hemostatic efficacy in the first 24 hours as good or excellent in 72% of the PCC group and in 65% of patients on plasma, a nonsignificant difference.
Thromboembolic event rates through 51 days of follow-up were 7.8% with the PCC and 5.5% with plasma.
Dr. Goldstein reported that he serves as a consultant to and advisory board member for CSL Behring, which markets Beriplex and sponsored the study.