Giant electron dense chains, clusters and granules in megakaryocytes and platelets with normal dense bodies: an inherited thrombocytopenic disorder IV. Ultrastructural cytochemistry and analytical electron microscopy.

Platelets from a mother and son with prolonged thrombocytopenia were shown in previous studies to contain giant organelles that developed in megakaryocytes and continued to evolve in circulating cells. Whole mount platelet preparations revealed that the large organelles were electron opaque like the serotonin-rich dense bodies in normal and patient platelets, and analytical electron microscopy revealed they contained large amounts of calcium and phosphorous in a ratio close to that found in normal platelet dense bodies. However, differences in physiology, biochemistry and morphology indicated the large opaque bodies and target-organelles in patient platelets were not aberrant dense bodies. The present study has shown that the giant organelles contain peroxidase activity like primary lysosomes in polymorphonuclear (PMN) leukocytes. Further, the giant organelles in patient platelets contain acid phosphatase activity. Analytical electron microscopy demonstrated that cerium, the capture ion for the acid phosphatase reaction product, was present in the opaque organelles with calcium and phosphorous, but not present in their normal dense bodies. Since normal sized lysosomes appeared to be reduced in patient platelets, it was concluded that the large structures were abnormal lysosomes, or fused with normal platelet lysosomes during their development. Similar giant lysosomes were not present in other patient blood cells. As a result the disorder can be considered a unique lysosomal disease of platelets.