Very high-density platelets determine reactivity and activity of circulating platelets

Abstract

AbstractBackgroundFor many decades, platelets have been known to display a substantial density heterogeneity. Knowledge about the origins and functions of specific platelet density subpopulations is scarce. This study investigates if very high-density (1.09 kg/L) platelets impact upon the reactivity and activity of all platelets.MethodsSubjects (n=52) were recruited in conjunction with a nurse-guided blood pressure control. Platelet reactivity in citrate anticoagulated whole blood, i.e. surface-bound P-selectin after provocation, was analysed using a flow cytometry technique. ADP (8.5 μmol/L) was employed as an agonist. Subsequently, the entire population was separated according to density into 17 subpopulations, with fraction 1 containing the densest platelets (1.09 kg/L). In each subfraction surface P-selectin expression was determined. Subjects were then divided according to the number of very high-density platelets in 1.09high(n=17) and 1.09low(n=35) demonstrating >8×109/L and ≤8×109/L 1.09 kg/L fraction 1 platelets, respectively.ResultsSurface-attached P-selectin after provocation reveals that 1.09highassociates with increased whole blood reactivity of the entire platelet population. The level of significance wasp≤0.01 (8.5 μmol/L ADP). Furthermore, 1.09highrelates to increased spontaneous activity of density populations, as evidenced by membrane-bound P-selectin. For the fractionsnos. 2, 4-7, 9, 10 the differences were significant, withp-values ranging fromp≤0.05 top≤0.01.ConclusionThe number of very high-density (1.09 kg/L) platelets reflects the reactivity of the entire population. It is also closely related to subfraction P-selectin activity. It is unlikely that platelets gain density when circulating. Therefore, evidence suggests that very dense cells are created for this purpose at thrombopoiesis. It is tenable that such platelets regulate the reactivity of the entire population.