• Br J Anaesth · Feb 2014

    Augmentation of thrombin generation in neonates undergoing cardiopulmonary bypass.

    • N A Guzzetta, F Szlam, A S Kiser, J D Fernandez, A D Szlam, T Leong, and K A Tanaka.
    • Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA, USA.
    • Br J Anaesth. 2014 Feb 1;112(2):319-27.

    IntroductionFactor concentrates are currently available and becoming increasingly used off-label for treatment of bleeding. We compared recombinant activated factor VII (rFVIIa) with three-factor prothrombin complex concentrate (3F-PCC) for the ability to augment thrombin generation (TG) in neonatal plasma after cardiopulmonary bypass (CPB). First, we used a computer-simulated coagulation model to assess the impact of rFVIIa and 3F-PCC, and then performed similar measurements ex vivo using plasma from neonates undergoing CPB.MethodsSimulated TG was computed according to the coagulation factor levels from umbilical cord plasma and the therapeutic levels of rFVIIa, 3F-PCC, or both. Subsequently, 11 neonates undergoing cardiac surgery were enrolled. Two blood samples were obtained from each neonate: pre-CPB and post-CPB after platelet and cryoprecipitate transfusion. The post-CPB products sample was divided into control (no treatment), control plus rFVIIa (60 nM), and control plus 3F-PCC (0.3 IU ml(-1)) aliquots. Three parameters of TG were measured ex vivo.ResultsThe computer-simulated post-CPB model demonstrated that rFVIIa failed to substantially improve lag time, TG rate and peak thrombin without supplementing prothrombin. Ex vivo data showed that addition of rFVIIa post-CPB significantly shortened lag time; however, rate and peak were not statistically significantly improved. Conversely, 3F-PCC improved all TG parameters in parallel with increased prothrombin levels in both simulated and ex vivo post-CPB samples.ConclusionsOur data highlight the importance of prothrombin replacement in restoring TG. Despite a low content of FVII, 3F-PCC exerts potent procoagulant activity compared with rFVIIa ex vivo. Further clinical evaluation regarding the efficacy and safety of 3F-PCC is warranted.

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