Microscopic measurements of platelet aggregation reveal a low ADP-dependent process distinct from turbidometrically...

Platelet aggregation measured from the decrease in the number of nonaggregated platelets (PA) is compared with that measured from the increase in %T (TA) after ADP addition to a stirred platelet suspension. A number of properties distinguish PA from TA. Half-maximal extent of PA, measured at 3 or 10 sec after ADP addition is attained at significantly lower ADP concentrations ([ADP]) than for TA (velocity and extent), and in particular at [ADP] equal to or less than that required for shape change. PA appears minimally refractory to ADP under conditions causing maximal refractoriness of TA. Examination of the effect of three inhibitors of platelet aggregation acting on extracellular ionized calcium (EDTA) and on platelet adenylate cyclase (PGE1) and phosphodiesterase (anagrelide; BL-4162A) indicates that PA is generally less sensitive to these inhibitors than TA but, of greater significance, that PA and TA reveal aggregation processes with differing ADP sensitivities. It is suggested that these differences reflect different processes determining the strength of interplatelet interactions. Conventional aggregometry is insensitive for measuring the low ADP-dependent aggregation process.