Propensity for young reticulated platelet recruitment into arterial thrombi

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 (3,350 s^?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.