Age-related changes in platelet function are more profound in women than in men

Age affects most cellular processes but the effect of age on platelet function is unclear. Most studies to date have used non-physiological approaches such as light transmission aggregometry (LTA) or flow cytometry to investigate age-related changes in platelet function1,2,3,4. These studies have reported that aging results in significant increases in the release of plasma β-thromboglobulin (βTG), plasma platelet factor 4 (PF4), phosphoinositide turnover, platelet aggregation and plasma fibrinogen5,6,7. Ideally assays of platelet function should replicate the flow and shear environment that platelets experience in vivo. The platelet function analyser, the PFA-100 assesses platelet function under high-shear conditions. The device measures the time taken for platelets to occlude an aperture that is coated with either collagen and epinephrine (CEPI) or collagen and ADP (CADP). The results of the PFA-100 are reported as closure time (CT)8. A number of studies have used the PFA-100 to assess age-related changes in platelet function. However, the results of these studies are inconsistent. For example, a PFA-100 study of healthy Koreans (n = 78 males and 42 females), identified that older Koreans (>40 years) had platelet CT’s that were significantly shorter than those observed in younger populations. The study also concluded that females had longer CT’s compared to males9. In contrast to this study in healthy Koreans, Sestito and colleagues investigated the effects of age and gender on platelet CTs in 62 apparently healthy individuals (n = 33 males and 29 females), 35 to 75 years of age. The results of that study demonstrated an absence of correlation between age, gender and platelet CT10. During vascular damage, vascular matrix proteins are exposed to the flowing blood plasma. Von Willebrand Factor (VWF) by binding to the exposed subendothelial matrix, tethers circulating platelets in flow via the platelet GPIbα receptor11. These initial interactions between VWF and the platelet are short-lived, resulting in platelet translocation (stop/start motion of the platelet) as GPIbα-VWF bonds are formed and broken12. The net result is activation and adhesion of the platelet to the exposed surface13. Our research group has developed a Dynamic Platelet Function Assay (DPFA), using novel parallel plate flow chambers coated with immobilised human VWF and custom-designed platelet tracking software14. This system measures platelet translocation behaviour on VWF. In this study, we employed the above approach to investigate the effect of age on platelet function in over 100 healthy donors. Four novel parameters relating to the different stages of platelet interaction with VWF were measured.