No abstract

Blood can become hypercoagulable by shear-induced platelet activation and generation of microparticles. It has been reported that non-physiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25Pa, 125Pa) with an exposure time of 0.5 sec., generated by using a novel blood shearing device. Platelet activation (P-selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear-induced vWF damage was characterized with western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWM) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis while the reduction in platelet receptors and the loss of HMWM-vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices.

The nonphysiological mechanical shear stress in blood-contacting medical devices is one major factor to device-induced blood damage. Animal blood is often used to test device-induced blood damage potential of these devices due to its easy accessibility and low cost. However, the differences in shear-induced blood damage between animals and human have not been well characterized. The purpose of this study was to investigate shear-induced hemolysis of human and three commonly used preclinical evaluation animal species (ovine, porcine, and bovine) under shear conditions encountered in blood-contacting medical devices. Shear-induced hemolysis experiments were conducted using two single-pass blood-shearing devices. Driven by an externally pressurized reservoir, blood single-passes through a small annular gap in the shearing devices where the blood was exposed to a uniform high shear stress. Shear-induced hemolysis at different conditions of exposure time (0.04 to 1.5 s) and shear stress (25 to 320 Pa) was quantified for ovine, porcine, bovine, and human blood, respectively. Within these ranges of shear stress and exposure time, shear-induced hemolysis was less than 2% for the four species. The results showed that the ovine blood was more susceptible to shear-induced injury than the bovine, porcine, and human blood. The response of the porcine and bovine blood to shear was similar to the human blood. The dependence of hemolysis on shear stress level and exposure time was found to fit well the power law functional form for the four species. The coefficients of the power law models for the ovine, porcine, bovine, and human blood were derived.