POPULATION BALANCE ANALYSIS OF SHEAR-INDUCED PLATELET AGGREGATION
BELVAL, THOMAS K.
Doctor of Philosophy
The work herein examines in vitro platelet aggregation in response to fluid shearing motion. Our specific aim is to characterize shear-induced aggregation by means of kinetic measurements. In doing so we consider plausible physicochemical mechanisms for platelet activation in the shear field. Besides resolving some questions concerning the activation of platelets by shear forces, this study further implicates fluid mechanical factors in thrombosis and arterial disease. Specific results may also apply to the design and evaluation of blood-contacting artificial devices. The experimental procedure centers on the use of a rotational viscometer to apply a controlled shearing motion to platelet suspensions for prescribed times. We quantify aggregation through changes in particle size histograms and associated measures (e.g. total number of particles). Additional insight into the aggregation response comes from interpreting kinetic data using the coalescence equation, a population balance specific for particle aggregation. The coalescence equation gives rise to so-called "population balance measures" of aspects of particles pertinent to their aggregation behavior. For example, one measure indirectly assesses the adhesiveness of platelets during aggregation. Kinetic data from shear-induced aggregation indicate two population balance measures are important: the particle collison efficiency, (epsilon), and the particle void volume fraction, (phi). These and other kinetic measures indicate rapid activation (within ten seconds) of platelets in the shear field above a threshold shearing rate of about 2000 sec('-1) but diminishing platelet adhesiveness upon continued shear stress exposure. Moreover, aggregation in the shear field disappears at sufficiently low platelet concentrations (below about 60,000/mm('3) plasma), suggesting that chemical release or leakage from platelets may mediate shear-induced aggregation.