Heterogeneity Of Human Whole-Blood Platelet Sub-Populations .2. Use Of A Subhuman Primate Model To Analyze Relationship Between Density And Platelet Age

A subhuman primate model was devel- oped to ascertain whether or not platelet heterogeneity could be explained by aging in the peripheral circulation. Density- dependent platelet cohorts, postulated to represent cells of different ages, were iso- lated on isosmolar arabinogalactan gradi- ents and labeled with radiochromium. Mean platelet lifespan was measured for the different density cohorts, and simul- taneous sequential density distribution analysis was performed to follow changes in cell density during aging. The average mean lifespan of light platelets was 74.6 hr, compared to 313.6 hr for heavy platelets. After injection, labeled light platelets were recovered only in the gradi- ent light region, in contrast to labeled heavy platelets, which were initially re- stricted to the dense region and progres- sively migrated to the light region during their lifespan. This study supports the hypothesis that platelet age in unstressed primates correlates with cell density and provides a rationale for the use of "age- dependent" markers to estimate platelet turnover rates. T HE ORIGIN of platelet heterogeneity remains a controversial issue. Two hypotheses have been proposed based upon experimental and clinical observations. Karpatkin and co-workers"2 presented data to support the theory that platelets undergo an aging process in the peripheral circulation that gives rise to heterogeneity of platelet properties. In contrast, Pennington and co- workers,3'4 Paulus,5 and Boneu and co-workers6'7 concluded from their observa- tions that the major determinant of platelet heterogeneity is megakaryocyte heterogeneity. Resolution of this controversy is important to an understanding of platelet heterogeneity, since if cellular heterogeneity is the result of aging, then the use of platelet "age-dependent" markers may be of diagnostic value to estimate platelet turnover rates in a variety of disease states. Recent methodologic developments in this laboratory have made it possible to examine the relationship between buoyant density and platelet age and to determiie if aging in the peripheral circulation correlates with changes in plate- let properties.8 The rhesus monkey (Macaca mu/alta) was chosen as an ex- perimental model because of its hematologic similarity to man.9 Density- dependent platelet cohorts were isolated on isosmolar arabinogalactan gradients, labeled with radiochromium, and injected into donor animals and their survival was measured. After introduction of a labeled density cohort into a recipient, total whole blood platelets were periodically isolated and fractionated into four