Acquired
von Willebrand disease (aVWD) is a rare
bleeding disorder that mimics congenital VWD in previously healthy individuals; it is most frequently associated with
monoclonal gammopathy.
Hemostatic therapy of aVWD is challenging due to the extremely shortened half-life of endogenous and exogenous VWF. High-dose
intravenous immunoglobulin (
ivIG) is recommended as the treatment of choice, usually rapidly normalizing coagulation; but in case of failure, alternative treatment options are not well explored. We report successful major
orthopedic surgery in a 61-year-old woman with
multiple myeloma IgG lambda and aVWD.
IvIG alone failed to correct hemostasis. However,
ivIG pretreatment improved the VWF
ristocetin cofactor (VWF:RCo) half-life from only 1.5 hr to more than 4 hr, allowing
desmopressin infusions twice daily to maintain sufficient VWF:RCo levels. Because of diminishing
desmopressin effect, we attempted for the first time in aVWD a continuous VWF/FVIII infusion (Haemate HS), 2.1-2.7 FVIII U/kg/hr or 51-64 U/kg/day, respectively 4.6-6.0 VWF:RCo U/kg/hr or 110-145 U/kg/day) to reach constant factor levels. The steady-state clearance was 2.4 mL/kg/hr for FVIII:C and 13.5 mL/kg/hr for VWF:RCo. During surgery, VWF:RCo, FVIII:C, and PFA-100 closure time were normalized. Until day 5, VWF:RCo was kept above 50%, from day 6 to 10 at least 30% activity were attained. FVIII:C levels were always >70%. The
clinical course was uneventful without
bleeding. Two weeks after hip surgery the patient was discharged from the hospital without complaints. The
therapy described can be recommended as safe and feasible for further evaluation in aVWD patients who are hyporesponsive to
ivIG treatment alone. Continuous VWF/FVIII infusion can improve substitution
therapy in aVWD.