Platelet pathology in sex-linked GATA-1 dyserythropoietic macrothrombocytopenia I ultrastructure.

Various mutations in the X-linked transcription factor, GATA-1, may result in dyserythropoietic anemia, macrothrombocytopenia and/or erythropoietic porphyria. The present study has carried out detailed ultrastructural studies of abnormal platelet morphology in one, previously described family with a GATA-1 G208S mutation. The ultrastructural investigations revealed a large proportion of their circulating platelets were hypogranular macrothrombocytes, resembling cells from patients with the Gray Platelet Syndrome. However, most of their platelets contained some alpha granules and a small number contained as many as are present in normal platelets. GATA-1 platelets from family members also contained tubular inclusions formed from elements of the dense tubular system like those observed in the Medich Giant Platelets Disorder. The unique pathology of the GATA-1 family platelets found in this study involved features never observed previously in normal or abnormal platelets. Many of their cells contained unusual flat, tubular membrane sheets, often in parallel association and differing from all other membrane systems in normal platelets and megakaryocytes. In some macrothrombocytes the unusual membranes appeared to isolate areas of cytoplasm. The sequestered areas were platelets within platelets. On rare occasion there were two platelets within one platelet, or, even more rarely, a platelet within a platelet within a platelet. Another unique feature, probably related to platelets within platelets, was the frequent attachment of non-activated platelets to each other to form macrothrombocytes. GATA-1 platelets within platelets and attached to platelets, as well as giant platelets, suggest that proplatelet formation may be abnormal, or that GATA-1 platelets are unable to pinch off from megakaryocyte proplatelets in a normal manner.