Glanzmann thrombasthenia: deficient binding of von Willebrand factor to thrombin-stimulated platelets.

Abstract

Glanzmann thrombasthenia is an inherited bleeding disorder characterized by the failure of platelets to aggregate in response to almost all stimuli. Thrombasthenic platelets aggregated with bovine and porcine von Willebrand factor (vWF) and showed normal ristocetin-induced binding and aggregation in the presence of human vWF. The specific binding of vWF to the thrombin-stimulated platelets was < 20% of normal in 3 patients with Glanzmann thrombasthenia. Analysis of binding isotherms was based on the assumption of 1 class of binding sites for vWF on the platelet membrane. Double-reciprocal plots were used to calculate maximal binding at saturation and apparent Kd. In 9 normals, 2.82 .+-. 0.64 .mu.g (.+-. SD) of vWF bound to 108 platelets at saturation, with Kd (.+-. SD) = 3.65 .+-. 1.23 .mu.g/ml. In 2 patients with thrombasthenia, binding was markedly decreased and did not approach saturation. In the 3 patients, binding at saturation corresponded to 0.21 .mu.g/108 platelets, with Kd = 3.93 .mu.g/ml. Mechanisms underlying the vWF-platelet interaction are incompletely reflected in ristocetin-dependent assay systems. The platelet defect in Glanzmann thrombasthenia is apparently not limited to decreased binding of fibrinogen but involves several glycoproteins that are known to interact with platelets.