PLATELET SIZE, NOT PLATELET MASS, DETERMINES INTRINSIC KINETIC DIFFERENCES IN PLATELET RECRUITMENT INTO AGGREGATES FOR ADP, U46619, AND PAF, BUT NOT FOR RISTOCETIN

Previous studies of platelet aggregation using resistive counting methods (PA) have suggested a dependence on platelet size (v), but have not been evaluated for varying platelet number (N_o) and associated total platelet mass. Here, the relationship between v, N_o and function was examined in size dependent human subpopulations fractionated by counterflow centrifugation. The original platelet population and three size dependent platelet fractions were concentrated and resuspended into autologous citrated platelet poor plasma at varying N_o for 5 donors. The initial rate and sensitivity of PA were determined generally at 3-5 seconds following ADP/ristocetin addition. Extent of PA was determined at 10 seconds. At similar N_o (180 ± 50 × 10³ μl), large platelets (L;v = 7.4 ± 0.3 f1; 16 ± 4% of total population) were two-fold more sensitive and more rapidly recruited into both PA and turbidometrically measured macroaggregates (TA) in response to ADP than the smallest platelets (S;v = 4.6 ± 0.4; 16 ± 5%). Aggregation kinetics and sensitivity for the mid-sized platelets (v = 5.9 ± 0.3; 31 ± 7%) were intermediate between the large (L) and small (S) platelet fractions. When platelet counts were adjusted to yield similar total platelet mass (N_o × v), these differences persisted for PA, but not for TA. Subsequent studies were all made for platelet suspensions at similar mass. Maximal rates of ADP-induced shape change were comparable for L vs. S platelets. Significant differences in the initial rate and maximal extent of PA between the size-dependent fractions were also seen for a stable PGH₂ analogue (U46619) and platelet activating factor (PAF). Most platelets were maximally recruited into micro-aggregates (60-80% PA) for all sized fractions. Kinetics and sensitivity for ristocetin-induced agglutination were comparable between the different sized fractions. The above size-dependent differences in aggregation for physiological activators appear to arise from intrinsic membrane/cell biochemical differences, not observed for ristocetin-von Willebrand (Factor VIII)-induced agglutination.