Platelet activation risk index as a prognostic thrombosis indicator.

K. E. Zlobina,G. Th. Guria

doi:10.1038/srep30508

Abstract

Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. Despite the large amount of experimental data that have been obtained, the value of the critical shear rate, above which von Willebrand factor starts to activate platelets, is still controversial. Here, we recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We derived a diagram of platelet activation according to the shear rate and von Willebrand factor multimer size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced. This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Probable medical applications of the platelet activation risk index as a universal prognostic index are discussed.

Highlights

Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor
By applying the approach developed by De Gennes[28] and his colleagues[29] to the Von Willebrand factor (VWF) dynamics under shear stress conditions on the surface of platelets, we obtained for the first time the exact expression (4) for the dependence of the critical shear rate of platelet activation on VWF multimer size
We propose that the clustering and cooperative action of platelet GPIb receptors occurred due to their binding to a sufficient amount of A1 domains on the VWF multimer

Summary

OPEN Platelet activation risk index as a prognostic thrombosis indicator

Platelet activation in blood flow under high, overcritical shear rates is initiated by Von Willebrand factor. We recommend a theoretical approach to elucidate how the critical blood shear rate is dependent on von Willebrand factor size. We succeeded in deriving an explicit formula for the dependence of the critical shear rate on von Willebrand factor molecule size. The platelet activation risk index was introduced This index is dependent on the flow conditions, number of monomers in von Willebrand factor, and platelet sensitivity. Von Willebrand factor (VWF) plays a central role in transmitting the dynamic effect of blood flow shear stress to intracellular platelet activation pathways[6,7,8,9,10,11,12,13]. Following an increase in shear rate, it unfolds into an elongated form, which has an increased binding ability[16,17] (Fig. 1)

Ff is the folding force and

Von Willebrand factor unfolding

The curve

Platelet activation

Discussion

Additional Information