In this study, the clinical history of two patients with the
gray platelet syndrome, a rare
congenital disorder associating thrombopathia and
myelofibrosis is recalled. Complementary studies on platelets and megakaryocytes were performed, mainly with an immunocytochemical approach. In gray platelets, a general decrease of alpha-granule
proteins, including PF4, beta tg and PDGF was observed. The decrease in platelet mitogenic activity (PDGF) was confirmed by
biological and radio-immunological measurements. An abnormally high level of these compounds was also found in the plasma. In megakaryocytes cultured from the bone marrow of these patients, alpha-granule
proteins were normally expressed in early maturation stages, whereas they were found to be absent in the mature megakaryocytes. An alpha-granule
membrane glycoprotein, GMP 140 has been studied in resting and
thrombin stimulated gray platelets and was found to be normally expressed at the surface of stimulated platelets. GMP140 was studied in resting platelets by immunoelectron microscopy and found to be present in vacuole probably corresponding to empty granules. This observation allows to conclude that alpha-granule membrane is formed in the
gray platelet syndrome, but that there is a storage defect of alpha-granule soluble
proteins, possibly due to an abnormal targetting of these
proteins to the alpha-granule. Synthesis and subsequent release of these
proteins, namely of the mitogenic factors, which can induce
myelofibrosis and lung
fibrosis by abnormal fibroblast stimulation, is discussed.