Shear-induced platelet receptor shedding by non-physiological high shear stress with short exposure time: Glycoprotein Ibα and glycoprotein VI

Abstract

IntroductionThe structural integrity of platelet receptors is essential for platelets to function normally in hemostasis and thrombosis in response to physiological and pathological stimuli. The aim of this study was to examine the shedding of two key platelet receptors, glycoprotein (GP) Ibα and GPVI, after exposed to the non-physiological high shear stress environment which commonly exists in blood contacting medical devices and stenotic blood vessels. Materials and MethodsIn this in vitro experiment, we exposed healthy donor blood in our specially designed blood shearing device to three high shear stress levels (150, 225, 300Pa) in combination with two short exposure time conditions (0.05 and 0.5sec.). The expression and shedding of platelet GPIbα and GPVI receptors in the sheared blood samples were characterized using flow cytometry. The ability of platelet aggregation induced by ristocetin and collagen related to GPIbα and GPVI in the sheared blood samples, respectively, was evaluated by aggregometry. Results and ConclusionsCompared to the normal blood, the surface expression of platelet GPIbα and GPVI in the sheared blood significantly decreased with increasing shear stress and exposure time. Moreover, the platelet aggregation induced by ristocetin and collagen reduced remarkably in a similar fashion. In summary non-physiological high shear stresses with short exposure time can induce shedding of platelet GPIbα and GPVI receptors, which may lead platelet dysfunction and influence the coagulation system. This study may provide a mechanistic insight into the platelet dysfunction and associated bleeding complication in patients supported by certain blood contacting medical devices.