ACQUIRED VON-WILLEBRAND-FACTOR DEFICIENCY DURING HIGH-DOSE INFUSION OF RECOMBINANT FACTOR-VIII

Constant infusion of factor VIII (FVIII) into patients with haemophili a A after major surgery has been recommenced as optimal treatment to a void peaks and valleys in the circulating levels of FVIII and to allow the use of much lower doses of FVIII than are historically required. One of our young patients with severe (<0.01 U/ml FVIII) haemophilia s uffered a subdural haematoma for which he received treatment with 815 190 recombinant FVIII (rFVIII) units over a period of 52 d. weeks afte r admission, because of low FVIII levels and the presence of FVIII inh ibitors, the infusion rate was increased to > 100 U/kg/h for 14d. Duri ng this time the FVII level fluctuated between 0.6 and 4.2 Aml. For so me period it was not possible to detect ristocetin co-factor (VWF) lev el and VWF multimer pattern resembled those of a patient wit von Wille brand's disease. Subsequently, when the rFVII dose was increased 2-fol d. this was not reflected by the plasma level of FVIII although antibo dies were not detected. The data suggest that the prolonged infusion o f very high levels of rFVIII which is deficient in von Willebrand fact or can result in depletion of VWF form existing stores. producing a la boratory picture which is consistent with absence of complexing with V WF, FVIII appears to be cleared from the circulation at an increased r ate. This is expensive and potentially compromising. Therefore, when a dministering very high doses of FVIII concentrates devoid of VWF level s should be monitored.