Summary
New methodology for a quantitative description of adenosine diphosphate (ADP)- induced
human blood platelet aggregation in vitro is presented. The method uses electronic particle size analysis to determine the
relative amounts of and distribution of sizes among platelets and aggregates after
rapid termination of the events of ADP-induced aggregation by glutaraldehyde. Glutaraldehyde
is found to preserve the state of platelets and aggregates in suspension unchanged
for up to 48 h.
Descriptions of platelet aggregate sizes and amounts at many points during reversible
and irreversible aggregation at 37° C as they occur in the Platelet Aggregometer are
discussed. A new model of reversible platelet aggregation emerges revealing previously
unrecognized details of both the aggregation and disaggregation phases of the phenomenon
and establishing that disaggregation is not simply the ‘mirror image’ of aggregation.
Furthermore, the reactive proportions of the platelet population under conditions
of both ADP- induced reversible and irreversible aggregation are very similar, strongly
suggesting that other factors are responsible for the observed large differences in
aggregation rates and resulting aggregate sizes. Correlations between Platelet Aggregometer
parameters and the aggregate size distributions are considered, and the first report
of a correlation between the average platelet composition of particles in the aggregated
suspensions and the absorbance change as recorded by the Aggregometer is made. Also,
the relationship between particle concentration of a suspension of platelets and aggregates
and the suspension absorbance is non-linear. Heretofore unrecognized limitations of
the Platelet Aggregometer are revealed. Importantly, absorbance as measured by the
Aggregometer does not uniquely represent the magnitude of formed aggregates.