The parameters to diagnose
von Willebrand disease (vWD) include
factor VIII coagulant activity (FVIII:C),
von Willebrand factor antigen (vWF:Ag),
von Willebrand factor ristocetin cofactor activity (vWF:RCo), and
von Willebrand factor collagen binding activity (vWF:CB). Type 2 vWD is associated with a moderate
bleeding diathesis due to low levels of vWF:RCo and vWF:CB as compared with near normal or normal values for FVIII:C and vWF:Ag. As the
factor VIII/von Willebrand factor (vWF) concentrate,
Haemate-P, is featured by a vWF:RCo/FVIII:C ratio of about 2.2, the recommended loading dose of 50 U/kg FVIII:C followed by 25 U/kg FVIII:C every 12 h for several days for
bleeding prophylaxis in type 2 vWD patients undergoing major surgery demonstrated a predicted significant over-treatment reaching vWF:RCo levels above 2 U/ml. Therefore, we restricted
Haemate-P substitution for major surgery to one loading dose of 40-50 U/kg FVIII:C (88-110 U/kg vWF:RCo) followed by 15-20 U/kg FVIII:C (33-44 U/kg vWF:RCo) every 12 h for several days and evaluated this strategy in a prospective pharmacokinetic and efficacy study for
bleeding prophylaxis in five type 2 vWD patients. Pre-treatment and peak levels (1 h after
Haemate-P loading dose) rose from 0.43-0.66 to 1.5-2.5 U/ml for FVIII:C, from 0.23-0.45 to 1.5-2.5 U/ml for vWF:Ag, from 0.10-< 0.20 to 1.5-2.5 U/ml for vWF:RCo, and from < 0.05-0.10 to 1.0-2.0 U/ml for vWF:CB. Mean in vivo recoveries per transfused IU FVIII:C/kg
body weight were 3.2% for FVIII:C, 3.9% for vWF:RCo, and 2.8% for vWF:CB. Mean in vivo recoveries per transfused IU vWF:RCo/kg were 1.45% for FVIII:C, 1.7% for vWF:RCo and 1.25% for vWF:CB. The
biological half-life times after transfused
Haemate-P were about 12 h for both vWF:RCo and vWF:CB. Based on these pharmacokinetic data, we propose to adapt the loading dose
factor VIII/vWF concentrate (
Haemate-P) to 60-80 U/kg vWF:RCo followed by 30-40 U/kg vWF:RCo every 12 h for no longer than several days (less than 1 week) for
bleeding prophylaxis during major surgery or
trauma, and to one loading dose of 40-60 U/kg vWF:RCo for
minor surgery,
trauma or mucotaneous bleedings in patients with type 2 vWD unresponsive to
DDAVP.