AGGREGATION AND DISAGGREGATION KINETICS OF HUMAN BLOOD-PLATELETS .3. THE DISAGGREGATION UNDER SHEAR-STRESS OF PLATELET AGGREGATES

In the preceding two papers (1, 2), a population balance equation (PBE) mathematical model was developed, validated, and applied to the analysis of platelet aggregation kinetics under the influence of hydrodynamic shear stress. The present work involves the application of the model to the analysis of platelet reactions under shear stress in circumstances where disaggregation processes are of dominant importance: the disaggregation of aggregates formed in response to added agonists. Aggregation-disaggregation experiments were performed in the constant shear field of a rotational viscometer, and the evolution of the particle size distribution was determined by use of an electronic particle counter. The PBE model was used to simulate the experimental results. Exploratory calculations made it possible to reduce a rather complete, complex model to a more tractable form which retains the capability of simulating the experimental observations. For the experimental conditions studied, disaggregation by a splitting mechanism was found to be of dominant importance. The surface erosion mechanism can be neglected without significant impact on results. Physical reasoning confirmed by exploratory calculations showed that a discontinuous form of the breakage rate expression which incorporates a minimum friable particle size, gives significantly better results than a continuous expression. A simple step function void fraction parameter was found to be at least as successful as a more complicated, continuous function. The resulting simplified model has the potential of increasing our understanding of kinetics and mechanisms of platelet reactions, and of characterizing the state of platelet activity. Hence, it may be useful in efforts to understand thrombotic and hemostatic processes.