Intermittent injections vs. continuous infusion of factor VIII in haemophilia patients undergoing major surgery

Continuous infusion (CI) of factor VIII (FVIII) has been proved to be a safe alternative to intermittent bolus injections (BI) in haemophilia A. Most reports on CI suggest a considerable saving in FVIII compared with historical controls treated with BI, but some recent reports failed to demonstrate such an effect. The present study prospectively compared safety, efficacy and factor requirements in 43 major surgical procedures performed in severe haemophilia A patients who were treated with either BI (18 operations) or CI (25 operations). The aim was to maintain factor VIII levels above the same minimum levels. Improved safety of CI over BI was observed, despite a bias in favour of the BI group (all underwent unilateral operations, compared with 24% of the CI group who underwent bilateral operations). Higher nadir levels were found in the CI group (0.44 +/- 0.06 vs. 0.31 +/- 0.09 IU/ml; P < 0.01) with a lower incidence of dangerous drops below 0.3 IU/ml (8% vs. 44% of patients respectively; P < 0.01), and a lower drop in haemoglobin (Hb) (1.56 +/- 1.21 vs. 3.01 +/- 2.13 g/dl; P < 0.05) and blood transfusion requirements (12% vs. 39%; P < 0.01). Major bleeding complications developed in three out of 18 patients (17%) in the BI group and none of the CI group (P = 0.06). The FVIII dosage was lower by 36% in the CI group (467 +/- 104 vs. 733 +/- 126 IU/kg; P < 0.01). Had the trough factor levels been maintained at the target levels, a greater difference of 72% would probably have been observed.