Glanzmann thrombasthenia is an inherited
bleeding disorder characterized by the failure of platelets to aggregate in response to almost all stimuli. However, thrombasthenic platelets will aggregate with bovine and porcine
von Willebrand factor (vWF) and will show normal
ristocetin-induced binding and aggregation in the presence of human vWF. In contrast, we now report that the specific binding of vWF to the
thrombin-stimulated platelets was less than 20% of normal in three patients with
Glanzmann thrombasthenia. Analysis of binding isotherms was based on the assumption of one class of binding sites for vWF on the platelet membrane. Double-reciprocal plots were used to calculate maximal binding at saturation and apparent dissociation constant (Kd). In nine normals, 2.82 +/- 0.64 micrograms (+/- SD) of vWF bound to 10(8) platelets at saturation, with Kd (+/- SD) = 3.65 +/- 1.23 micrograms/ml. In two patients with
thrombasthenia binding was markedly decreased and did not approach saturation. In the third patient, binding at saturation corresponded to 0.21 micrograms per 10(8) platelets, with Kd = 3.93 micrograms/ml. These findings suggest that mechanisms underlying the vWF-platelet interaction are incompletely reflected in
ristocetin-dependent assay systems. Moreover, these results, in addition to those previously reported for
fibronectin, suggest that the platelet defect in
Glanzmann thrombasthenia is not limited to decreased binding of
fibrinogen but involves several
glycoproteins that are known to interact with platelets.