Atypical variant of acquired von Willebrand syndrome in Wilms tumor: Is hyaluronic acid secreted by nephroblastoma cells the cause?

Acquired von Willebrand syndrome (AvWS) has been reported in eight children with Wilms tumor (nephroblastoma in four boys and four girls) at a mean ag e of 3.3 years (range, 0.33-9 years). Only three of eight patients with AvW S in Wilms tumor presented with mild mucocutaneous bleeding symptoms. The A vWS in seven children with Wilms tumor featured either undetectable or very low von Willebrand factor antigen (vWF.Ag) levels (mean, 3%) and decreased values for VWF ristocetin cofactor (RCF) activity (mean, 20%) and factor V III coagulant (VIIIc) activity (mean, 16%). The response to 1-desamino-8-ar ginine vasopressin (DDAVP) was good in two and poor in one patient. Multime ric analysis of the vWF showed a normal pattern of type I von Willebrand di sease (vWD) in three patients and an absence of multimers consistent with t ype III vWD in two patients. The higher functional levels, as compared with antigen levels, with increased ratios for factor VIIIc/vWFAg (mean, 5.3) a nd vWF.RCF/vWF.Ag (mean, 6.6) in seven patients with Wilms tumor are unexpl ained physiologically and are not consistent with type I vWF deficiency. Th e absence of vWD in the patient's family, and the return of factor VIII-vWF parameters to normal after chemotherapy or surgical removal of the Wilms t umor, support the diagnosis of AvWS causally related to the Wilms tumor. Th e causative agent is thought to be hyaluronic acid secreted by nephroblasto ma cells of the Wilms tumor. Prospective studies to determine the nature of AvWS in children with Wilms tumor are warranted.