Platelet Aggregation Induced by Plasma from Type IIB von Willebrand’s Disease Patients Is Associated with an Increase in Cytosolic Ca2+ Concentration

Maria Angela Francesconi; Renzo Deana; Antonio Girolami; Elena Pontara; Alessandra Casonato

doi:10.1055/s-0038-1649652

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(04): 697-701
DOI: 10.1055/s-0038-1649652

Original Article

Von Willebrand Factor And Endothelial Cells

Schattauer GmbH Stuttgart

Platelet Aggregation Induced by Plasma from Type IIB von Willebrand’s Disease Patients Is Associated with an Increase in Cytosolic Ca²⁺ Concentration

Maria Angela Francesconi

The Department of Biological Chemistry, University of Padua, Italy

,

Renzo Deana

The Department of Biological Chemistry, University of Padua, Italy

,

Antonio Girolami

¹Institute of Medical Semeiotics and Fourth Chair of Internal Medicine, University of Padua, Italy

,

Elena Pontara

¹Institute of Medical Semeiotics and Fourth Chair of Internal Medicine, University of Padua, Italy

,

Alessandra Casonato

¹Institute of Medical Semeiotics and Fourth Chair of Internal Medicine, University of Padua, Italy

› Author Affiliations

Abstract

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Summary

The effect of type IIB von Willebrand’s factor (vWF) on platelet cytosolic Ca²⁺ ion concentration, measured by means of the probe fura 2, was investigated. Seven patients with type IIB von Willebrand disease (vWD) were studied. Addition of type IIB vWD plasma to platelet suspensions induced a cytosolic calcium increase accompanied by platelet aggregation. Both processes were completely abolished by addition of the calciumchelating agent EGTA, indomethacin, peptide RGDS, and monoclonal antibodies blocking the vWF binding site on GPIb-IX (LJIB1) or the cytoadhesive receptor on GPIIb-IIIa (LJCP8). The ADP-scavenger apyrase and the protein kinase C-inhibitor staurosporine partially inhibited the rate of the cytosolic calcium increase. No direct correlation between the extent of Ca²⁺ rise and the phenotypic expression of IIB vWD, such as the degree of spontaneous platelet aggregation or thrombocytopenia was apparent. It is suggested that aggregation and cytosolic Ca²⁺ increase in platelets exposed to plasma from type IIB vWD patients is mediated by a self-potentiating mechanism involving both GPIb and GPIIb-IIIa receptors as well as the thromboxane biosynthetic pathway.

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References

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