Impact of infusion speed on the safety and effectiveness of prothrombin complex concentrate

Abstract

Prothrombin complex concentrate (PCC) infusion is preferred for emergency reversal of coumarin therapy. Rapid infusion can potentially save crucial time; however, the possible impact of high infusion speed on PCC safety and effectiveness has not been delineated. In a prospective multinational clinical trial with 43 patients receiving PCC (Beriplex® P/N) for emergency reversal of coumarin therapy, infusion speeds were selected by the investigators. In a twophase statistical analysis, the influence of baseline patient variables and dose on selected infusion speed was assessed. Then, the effect of infusion speed on reduction in international normalized ratio (INR) and on thrombogenicity marker pharmacokinetics was evaluated. Infusion speed ranged widely from 2.0 to 40.0 mL min −1 with a median of 7.5 mL min −1 . Selection of infusion speed was not significantly influenced by gender, age, body mass index, presence of acute bleeding, indication for coumarin therapy, baseline INR, or PCC dose. Infusion speed was higher by a median of 2.2 mL min −1 (95% confidence interval, 1.0-4.3 mL min −1 ) among patients receiving Beriplex P/N volumes ≥80 mL compared with smaller infusion volumes. Infusion speed did not affect INR attained 30 min following PCC infusion. None of the evaluated thrombogenicity marker pharmacokinetic parameters was affected by infusion speed. Infusions in one patient with questionable hemostatic efficacy and another with a possibly PCC-related thromboembolic event were at moderate and slow speeds, respectively. This study provides the first direct evidence that Beriplex® P/N can be rapidly infused for emergency coumarin therapy reversal without altering safety or effectiveness.

Prothrombin complex concentrates in emergency bleeding disorders

“…Bleeding secondary to VKA anticoagulation VKAs block the g-carboxylation of the procoagulant factors, II, VII, IX, and X, and the anticoagulant factor proteins, C and S [24,25]. All of these factors remain inactive in the absence of carboxylation.…”

Urgent warfarin reversal: know your options

“…Alternatively, observational studies of similar PCC products suggest that infusion rates two to three times faster than that recommended for OctaplexÒ may be safe. 23 Either way, it is important that patients receiving PCCs be monitored carefully for signs of thrombotic complications and have a post-infusion INR performed immediately to confirm that an adequate dose was given.…”

“…En revanche, des études observationnelles portant sur des produits de CCP similaires suggèrent que des débits de perfusion deux à trois fois plus rapides que ceux recommandés pour l'OctaplexÒ pourraient être sécuritaires. 23 Quoi qu'il en soit, il est important de surveiller de près les patients recevant des CCP pour dépister les signes de complications thrombotiques et de mesurer l'INR du patient immédiatement après la perfusion afin de confirmer qu'une dose appropriée a été administrée.…”

Emergency Management of Bleeding Associated With Old and New Oral Anticoagulants

“…13 In the setting of VKA-related hemorrhage, the principal objective is to increase the concentration of vitamin K-dependent clotting factors.…”

“…13,31 Prothrombin complex concentrates may be used for the rapid replacement of vitamin K-dependent clotting factors when excessive anticoagulation is related to a VKA. Second-generation PCCs contain both procoagulation and anticoagulation factors.…”