Studies of the platelet density abnormality in myeloproliferative disease.

We have previously shown that the extinction (optical density) of normal fresh platelets correlates closely with their apparent volume as determined with the Coulter counter and that platelets from patients with myeloproliferative disorders (MPD) have a decrease in extinction relative to their apparent volume. In this study we show that the reduction in extinction of MPD platelets correlates with a decrease in platelet density and with a decrease in the refractive index of the platelet hyaloplasm. To explore the abnormality of the hyaloplasm, we incubated normal and MPD platelets in plasma from blood anticoagulated with K3-ethylenediaminetetraacetate (EDTA). Normal platelets responded with marked swelling, as shown by an increase in apparent Coulter volume and by corresponding decreases in density, extinction, and refractive index of hyaloplasm. The magnitude of these changes was markedly less with MPD platelets. Ultrastructural studies by others have indicated that the swelling effect of EDTA results from dilatation of intracellular channels such as the surface-connected canalicular system and that these structures occupy more of the interior of MPD platelets than in the case of normal platelets. One hypothesis to explain our findings is that MPD platelets circulate with dilated internal channels that are unable to dilate further with EDTA. In addition, we previously found that MPD platelets display an increased dispersion (geometric standard deviation) of their apparent Coulter volumes. In this study we show that the dispersion abnormality correlates with the density abnormality and that the increase in dispersion is not confined to a subpopulation of abnormal light platelets; rather, it is present in all density subpopulations. All of our data are consistent with the view that the abnormalities in density and dispersion originate at the time of shedding from the megakaryocyte.