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

Z. M. Ruggeri, R. Bader, L. De Marco

Research output: Contribution to journalArticlepeer-review

Abstract

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 <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 (K(d). In nine normals, 2.82 ± 0.64 μg (± SD) of vWF bound to 10 8 platelets at saturation, with K(d) (± SD) = 3.65 ± 1.23 μg/ml. In two patients with thrombastenia binding was markedly decreased and did not approach saturation. In the third patient, binding at saturation corresponded to 0.21 μg per 10 8 platelets, with K(d) = 3.93 μg/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 Glanzmanmn thrombasthenia is not limited to decreased binding of fibrinogen but involves several glycoproteins that are known to interact with platelets.

Original languageEnglish
Pages (from-to)6038-6041
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume79
Issue number19 I
Publication statusPublished - 1982

ASJC Scopus subject areas

  • General
  • Genetics

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