Complementary Roles for Fibrin(ogen), Thrombospondin and vWF in Mediating Shear-dependent Aggregation of Platelets Stimulated at Threshold Thrombin Concentrations

Ana Kasirer-Friede; Chantal Legrand; Mony M. Frojmovic

doi:10.1055/s-0037-1616101

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 86(02): 653-659
DOI: 10.1055/s-0037-1616101

Review Article

Schattauer GmbH

Complementary Roles for Fibrin(ogen), Thrombospondin and vWF in Mediating Shear-dependent Aggregation of Platelets Stimulated at Threshold Thrombin Concentrations

Ana Kasirer-Friede

¹Depts. of Experimental Medicine and Physiology, McGill University, Montreal, Canada

,

Chantal Legrand

²Unité 353 INSERM, Institut Universitaire d’Hematologie (Paris VII-Denis Diderot), Hôpital St. Louis (AP-HP), Paris, France

,

Mony M. Frojmovic

¹Depts. of Experimental Medicine and Physiology, McGill University, Montreal, Canada

› Author Affiliations

Abstract

Summary

We have evaluated the relative contribution of the adhesive ligands, von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP), all surface-expressed on washed platelets (WP) activated with a threshold thrombin concentration (~ 0.04 U/ml), to platelet micro-aggregation (PA) at shear rates (G) from 300-2000 s^-1. In suspensions of thrombin-activated WP sheared immediately (τ₀), all three ligands were required for optimal aggregation at all G, as shown by a 50-70% inhibition of capture efficiencies of PA (measured from initial rates of PA), by antibodies (Abs) directed against each protein. This aggregation involved both GPIb and GPIIbIIIa, as indicated by ~ 80% and 100% inhibition by Ab 6D1 and Ab 10E5, respectively. For WP preexposed to thrombin for 10 min to ensure maximal surface expression of secreted ligands and activated GPIIbIIIa (τ₁₀), vWF was predominantly required at all G (63-75% inhibition by anti-vWF Ab), together with TSP (35-50% inhibition by anti-TSP Ab). Under these conditions, Fg was extensively converted to fibrin, so that fibrin, rather than Fg, could participate in microaggregation, with GPIb less required than GPIIbIIIa as indicated by a 30-60% inhibition by Ab 6D1 as compared to 100% inhibition by Ab 10E5. Our results show that interactions between multiple ligands and receptors favour microaggregation depending on shear and thrombin activation conditions.

Keywords

vWF - fibin(ogen) - thrombospondin

Full Text

References

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