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Continuous infusion of intermediate‐purity factor VIII in haemophilia A patients undergoing elective surgery
Author(s) -
Charles-Henry Rochat,
M L McFadyen,
R Schwyzer,
Anne Gillham,
Anne-Louise Cruickshank
Publication year - 1999
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1046/j.1365-2516.1999.00309.x
Subject(s) - medicine , pharmacokinetics , haemophilia , continuous infusion , haemophilia a , bolus (digestion) , anesthesia , volume of distribution , surgery , 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.