PLATELET AGGREGATION DOES NOT CONFORM TO SIMPLE PARTICLE COLLISION THEORY

Platelet aggregation kinetics, according to the particle collision theory, generally assumed to apply, ought to conform to a second order type of rate law. But published data on the time-course of ADP-induced single platelet recruitment into aggregates were found not to do so and to lead to abnormal second order rate constants much larger than even their theoretical upper bounds. The data were, instead, found to fit a first order type of rate law rather well with rate constants in the range of 0.04 - 0.27 s-1. These results were confirmed in our laboratory employing gelfiltered calf platelets. Thus a mechanism much more complex than hithertofore recognized, is operative. The following kinetic scheme was formulated on the basis of information gleaned from the literature.where P is the nonaggregable, discoid platelet, A the agonist, P* an aggregable platelet form with membranous protrusions, and P** another aggregable platelet form with pseudopods. Taking into account the relative magnitudes of the k*s and assuming aggregation to be driven by hydrophobic interaction between complementary surfaces of P* and P** species, a rate equation was derived for aggregation. The kinetic scheme and the rate equation could account for the apparent first order rate law and other empirical observations in the literature.