Strenuous exercise promotes shear-induced thrombin generation by increasing the shedding of procoagulant microparticles from platelets

Abstract

Vigorous exercise increases the risk of vascular thrombotic events. Shear stress enhances the shedding of procoagulant microparticles from platelets, and triggers thrombin generation (TG) in blood. This study explicates the manner in which strenuous exercise affects platelet-derived microparticles (PDMP) release and PDMP-mediated TG under various physio-pathological shear flows. Twenty-four sedentary healthy men performed a graded exercise test (up to VO2max) on a bicycle ergometer. At rest, immediately after and 2 hours after exercise, platelet-rich plasma (PRP) was exposed in a cone-and-plate viscometer to imitate static (0 dyne/cm2), physiological low (LS, 10 dyne/cm2) and pathological high (HS, 100 dyne/cm2) shear stresses ex vivo. The PDMP characteristics and dynamic TG were measured by two-colour flow cytometry and calibrated, automatic thrombinography, respectively. The results demonstrated that there is an increased level of total PDMP together with elevated peak height and rate of TG in PRP in response to both LS and HS conditions. Furthermore, HS, but not LS, promoted the binding of FV/Va or FVIII and the exposure of phosphatidylserine (PS) on platelets. Application of HS after strenuous exercise increased the factor (F)V/Va-/FVIII-/tissue factor-rich and PS-exposing PDMP counts, enhanced the PDMP-promoted peak height and rate of TG, as well as increased the ability of FV/Va or FVIII to bind to PDMP or platelets. However, the enhancement of HS-induced procoagulant activity reversed to the pre-exercise status 2 hours following this exercise. Therefore, we conclude that strenuous exercise modestly contributes to the acceleration of shear-induced TG by increasing the release of procoagulant microparticles from platelets.