Is platelet aggregation a more important contributor than platelet adhesion to the overall platelet-related primary haemostasis measured by PFA-100™?

Abstract

Background: Platelet-related primary haemostasis (PRPH), measured in PFA-100™ as a closure time (CT), reflects platelets' combined ability to adhere and aggregate under higher shear stress. The inputs of platelet aggregation and platelet adhesion into the real values of CT remain unknown, and this poor discrimination results in the complexity of the PFA-100™ measurement. Objective: To estimate the particular contributions of two physiological phenomena, platelet aggregation and adhesion, and the importance of various membrane receptors underlying platelets' capability of the plug formation in PFA-100™ cartridges. Materials and methods: Effects of various blockers antagonizing ligands binding to platelet surface membrane receptors (antagonists of GPIIb-IIIa complex, collagen receptors and purinoreceptors), and aurintricarboxylic acid (ATA), the antagonist of GPIb–von Willebrand factor (vWF) interaction, were monitored in 47 healthy donors with the use of PFA-100™ and whole blood electrical aggregometry (WBEA). Results: PFA-100™ collagen/ADP CT was the most sensitive in probing the effect of platelet membrane receptor antagonists acting via the blockade of GPIIb-IIIa complex and those antagonizing GPIb–vWF interaction (GR144053F, Integrilin, ATA), whereas the other blockers, acting on collagen receptors or purinoreceptors, remained much less efficient. For the examined GPIIb-IIIa and GPIb antagonists, the overall variability in WBEA explained a very significant part (30–60%) of the overall variability in PFA-100™ CT. Conclusions: GPIIb-IIIa-mediated platelet aggregation and von Willebrand factor interactions with GPIb and/or GPIIb-IIIa seem to be the major determinants of PFA-100™ CT. On the contrary, other platelet receptors participating in platelet aggregation and/or platelet adhesion are of secondary importance and minor significance in blood flow at higher shear stress monitored in PFA-100™.