Continuous infusion of intermediate-purity factor VIII in haemophilia A patients undergoing elective surgery

An open, non-randomized trial of continuous infusion therapy was conducted involving five patients with severe haemophilia A who required factor VIII (FVIII) prophylaxis for elective surgery. This was preceded by a 24-h preoperative pharmacokinetic study to characterize the pharmacokinetic parameters of each individual patient following a bolus dose of the intermediate-purity product. A retrospective matched control group was identified to allow for comparisons of FVIII usage between bolus and continuous infusion administration. A loading dose of FVIII was administered preoperatively, and the continuous infusion was started at the end of surgery and continued for 5 days. The patients' FVIII levels, vital signs, and infusion sites were monitored on a daily basis. The clearance was re-calculated on a daily basis using the FVIII activity of that day to adjust the infusion rate to achieve the desired FVIII level. The mean (CV%) pharmacokinetic parameters estimated preoperatively by noncompartmental analysis were: clearance 3.2 mL kg-1 h-1 (35.5%), volume of distribution 52.1 mL kg-1 (40.2%), mean residence time 17.4 h (23.3%), and half-life 12.7 h (23.6%). A progressive decrease in the clearance of FVIII from a mean of 3.1 mL kg-1 h-1 to 2.0 mL kg-1 h-1 (P = 0.125) over the first 5 days was observed. A therapeutically acceptable level of FVIII was systematically achieved, with the only complication being frequent thrombophlebitis. On average the patients used 19% less FVIII when compared with matched historical controls (P = 0.25). This method was found to be safe and effective in haemophilia A patients undergoing elective surgery procedures.