Von Willebrand's disease with thrombocytopenia, platelet function defect, and an abnormal Factor VIII molecule.

A girl with clinical and laboratory findings of severe Von Willebrand's disease (VWD) characterized by a prolonged bleeding time, marked reduction of both Factor VIII procoagulant activity and Factor VIII related antigen with an abnormal crossed immunoelectrophoretic factor VIII molecule (CIEP) is presented. Persistent thrombocytopenia and abnormal platelet function manifested during platelet aggregation with epinephrine, ADP and collagen and abnormal C14 serotonin and platelet factor 4 release were also noted. Family studies reveal both parents and a paternal aunt with low normal VWD parameters and normal immunoelectrophoretic factor VIII molecules. A sister has mild classical VWD. Both the father and paternal aunt have normal platelet counts but manifest a similar platelet functional defect. These findings suggest that our patient is homozygous for VWD and has inherited the platelet functional defect through the paternal side of the family. The addition of CIEP techniques may allow for further genetic clarification of the Von Willebrand syndromes; specifically, delineating the severe, homozygous Von Willebrand patient from the more common classical heterozygous patient and from the heterogeneous group of VWD patients with structural defects of the VWD factor. The genetic implications and the interaction of thrombocytopenia and abnormal platelet function in VWD are discussed.