A THROMBOCYTOPENIA (T) GIANT PLATELET SYNDROME WITH DEFECTIVE PLATELET AGGREGATION AND A VON WILLEBRAND (VW)-LIKE PLASMA DEFECT

A 17-year old girl with life-long T, unresponsive to splenectomy, was evaluated because of easy bruising, epistaxis, and recurrent hemarthroses. Platelets (P) were reduced in number (50,000-140,000/μl) and their size was greatly increased (3-5 μ in diameter) on peripheral blood smear. Bone marrow contained increased megakaryocytes, and 51chromium-labeled autologous P survival was normal (7.8 days), suggesting ineffective thrombopoiesis as the cause of the T. Bleeding time (BT) was consistently greater than 25 min., and P did not aggregate normally when incubated with collagen or epinephrine but did respond to ristocetin. Although rate of uptake of 3H-serotonin was reduced, P ATP/ADP ratio was normal, excluding a storage-pool defect. The patient's Factor VIII level measured by coagulation assay (VIIIAHF) or by ability of her plasma to support ristocetin-induced aggregation (VIIIVWF) varied from 35-150% and 27-160% respectively, while Factor VIII-related antigen was always normal (over 60%). Transfusions of both cryoprecipitate and P, but neither alone, transiently shortened BT (to 7-9 min.) and controlled bleeding symptoms. Post-transfusion increments in VIIIAHFwere consistent with VW disease. Family history and coagulation studies were unremarkable. This patient appears to have a unique combined defect in thrombopoiesis, in-trinsic P function, and in VIIIVWF. Effective therapy has required both normal P and Factor VIII-containing products.