TY - JOUR T1 - Very high-density platelets determine reactivity and activity of circulating platelets JF - bioRxiv DO - 10.1101/388744 SP - 388744 AU - P. Järemo Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/08/09/388744.abstract N2 - Background For 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.Methods Subjects (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.Results Surface-attached P-selectin after provocation reveals that 1.09high associates with increased whole blood reactivity of the entire platelet population. The level of significance was p≤0.01 (8.5 μmol/L ADP). Furthermore, 1.09high relates to increased spontaneous activity of density populations, as evidenced by membrane-bound P-selectin. For the fractions nos. 2, 4-7, 9, 10 the differences were significant, with p-values ranging from p≤0.05 to p≤0.01.Conclusion The 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. ER -