Newly recognized cellular abnormalities in the gray platelet syndrome

The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which thrombocytopenia is associated with increased platelet size and decre ased alpha -granule content. This report describes 3 new pediatric cases pr esenting with the classical platelet abnormalities of GPS within one family with normal parents, Examination of blood smears of the 3 patients demonst rated not only gray platelets, but also gray polymorphonuclear neutrophils (PMNs) with decreased or abnormally distributed components of secretary com partments (alkaline phosphatase, CD35, CD11b/CD18). Secondary granules were also decreased in number as assayed by immunoelectron microscopy. These da ta confirm that the secretary compartments in neutrophils were also deficie nt in this family. Megakaryocytes (MKs) were cultured from the peripheral b lood CD34(+) cells of the 3 patients for 14 days, In the presence of thromb opoietin and processed for immunoelectron microscopy. Although von Willebra nd factor (vWF) was virtually undetectable in platelets, vWF immunolabeling was conspicuous in cultured maturing MKs, particularly within Golgi saccul es, but instead of being packaged in a-granules, it was released Into the d emarcation membrane system. In contrast, P-selectin followed a more classic al pathway. Double-labeling experiments confirmed that vWF was following an intracellular pathway distinct from the one of P-selectin. In these 3 new cases of GPS, the MKs appeared to abnormally process vWF, with secretion in to the extracellular space instead of normal alpha -granule packaging. Furt hermore, the secretary compartment of another blood cell line, the neutroph il, was also affected In this family of GPS. (C) 2001 by The American Socie ty of Hematology.