Propensity for young reticulated platelet recruitment into arterial thrombi

Abstract

Atherosclerosis reduces platelet survival and thereby increases the percentage of younger platelets in the circulation assuming steady-state thrombocytopoiesis. We hypothesized that younger platelets have an increased propensity for arterial thrombus participation compared to older counterparts. Platelet-rich thrombi were generated by perfusing human heparinized whole blood from normal donors over arterial cross-sections under shear conditions (3,350s(-1)) corresponding to significant coronary artery stenosis using a perfusion chamber. Harvested thrombi were disaggregated, stained with thiazole orange, anti-integrin β3, glycoprotein (GP) Ibα, GP IX and P-selectin, and compared to paired whole blood samples from the same donor by flow cytometry. Thiazole orange staining intensity provides a measure of platelet m-RNA content and age. Thiazole orange staining intensity (MN±SEM) of platelets harvested from thrombi (62±13) was twofold greater compared to paired intra-individual whole blood samples (31±1). Integrin β3 receptor density was also greater for thrombus platelets (12.0±1.0) compared to whole blood platelets (7.0±0.6; p<0.0001). GPs Ibα and IX were reduced from thrombus platelets possibly reflecting shedding. Younger "reticulated" platelets appear to have a greater propensity for thrombus participation under shear conditions of coronary artery stenosis compared to older counterparts. This predisposition may be explained by an increased receptor density of integrin β3 in younger platelets. By this mechanism, the atherosclerotic process may enhance the individual propensity for arterial thrombosis.