We have identified a patient with
von Willebrand's disease (vWD) resembling type IIB vWD, with increased
ristocetin induced platelet aggregation (RIPA), the absence of the large multimers of
von Willebrand factor (vWF) in plasma, and the presence of the large multimers in platelets in whom a family study indicated a probable double heterozygous inheritance pattern. The propositus was a 12-year-old boy with frequent
epistaxis and bruising. Abnormal
hemostatic findings included a prolonged bleeding time (BT), decreased levels of
factor VIII coagulant activity (VIIIC),
von Willebrand factor antigen (vWF:Ag),
ristocetin cofactor (RCof), and an increased RIPA. In the presence of
ristocetin, binding of the patient's plasma vWF to normal platelets was increased but binding of normal vWF to his platelets was normal. SDS-
agarose gel (1.5%) electrophoresis revealed that plasma vWF lacked the large multimers, and 3.0% gel electrophoresis revealed that the multimers had a 5-band pattern similar to normal. The above findings were consistent with type IIB vWD, but 1-deamino[8-D-
arginine]-vasopressin (
DDAVP) infusion resulted in a shortened BT and the transient appearance of large multimers without a decrease in the platelet count. Family studies revealed that his mother has mild
bleeding symptoms, decreased VIIIC, vWF:Ag, and RCof levels and normal to slightly reduced RIPA with a multimer pattern consistent with type I vWD. In contrast, the father, sister, and paternal grandfather were asymptomatic, with a slightly decreased VIIIC level but a normal BT and vWF:Ag and RCof levels. Their RIPA and vWF binding to normal platelets were increased, but unlike the propositus their plasma contained large multimers. We concluded that the propositus is a type IIB-like variant differing from previously reported IIB variants in two ways: 1) his response to
DDAVP and 2) a possible double heterozygous mode of inheritance rather than the usual dominant route.