Correlation between chemical stimulation and filtration flow resistance in human platelet aggregates

Human platelet-rich plasma (PRP) was aggregated with ADP to produce varying degrees of reversibility and platelet release, and then the chemical stimulation (as evidenced by optical transmittance) was compared with the flow resistance of physiologically-significant microaggregates, determined by constant-pressure filtration. The aggregate flow resistance was attributed to "weak" aggregates (which occluded the micropore filter at 20 mm Hg but which passed through the filter at 80 mm Hg) and "strong" aggregates (which occluded the filter at 80 mm Hg). As the ADP concentration was increased from 1 microM to 10 microM, the flow resistance of both the "weak" and "strong" aggregates generally increased, as did the maximum transmittance. No consistent trend was seen as the time after ADP addition increased from 5 to 30 minutes. Pretreatment of the PRP with epinephrine increased the maximum transmittance during ADP aggregation, produced less-reversible aggregates (less subject to deaggregation by PGE1), and increased the aggregate flow resistance over the range of filtration pressures tested. The addition of PGE1 to the aggregated sample before filtration nearly eliminated the flow resistance of the aggregates at all filtration pressures tested and partially reversed the optically-apparent aggregation. Pretreatment of PRP with PGE1 before epinephrine or ADP addition inhibited both the optically-detected aggregation and the development of flow resistance. The physical (hydrodynamic) strength of platelet aggregates is apparently related to the chemical stimulation of the release reaction and to aggregation irreversibility, possibly through the mediation of adenylate cyclase and cyclic AMP.