Pharmacokinetics-Guided Perioperative Replacement Therapy in Hemophilia a Patients

Purpose: Pharmacokinetics(PK)-based prophylactic treatment has been proven to meet the pharmacoeconomics needs of patients with hemophilia to the greatest extent in recent years，but the way and significance of PK-guided perioperative replacement therapy remain unclear.

Methods:In this study, PK parameters (calculated by DAS software), including half-life and in vivo recovery(IVR), were used to guide individualized replacement therapy for surgical patients with hemophilia A. PK profiles were described by a two-compartment model. The collection of perioperative factor VIII(FVIII) plasma concentrations, factor consumption, and blood loss data was used to verify the efficacy of individualized programs.

Results:A total of 46 patients underwent 50 surgeries (median age: 32 years, median weight: 60.5 kg), all of which were major surgeries. The median half-life was 15.44h, and the median IVR was 2.29IU dl ^-1/IU kg ^-1. In total, 50 surgeries contributed with 528 plasma FVIII activity observations, of which 310 (58.71%) entered the target range. The median intraoperative blood loss of 43 surgeries was 446.9ml. No severe complications occurred during the perioperative period. Hematomas appeared after six surgeries, which have been resolved after treatment at discharge. Inhibitor developed in one patient and was transient. The median consumption of FⅧ concentrates during the perioperative period was 511.7U/kg, which reduced by 26.69% compared with the dosage based on weight (648.3U/kg, P＜0.001). During the perioperative period, the actual factor consumption was consistent with the PK-guided plan (P>0.05). In addition, a negative correlation was found between intraoperative blood loss and immediate postoperative FVIII activity (r= -0.477, P=0.001).

Conclusion: PK-guided perioperative replacement therapy in hemophilia A patients can safely and effectively reduce the consumption of FⅧ concentrates.

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