Newly recognized cellular abnormalities in the gray platelet syndrome

• Published in: Blood 2001-09, Vol.98 (5), p.1382-1391
• Main Authors: Drouin, Arnaud, Favier, Rémi, Massé, Jean-Marc, Debili, Najet, Schmitt, Alain, Elbim, Carole, Guichard, Josette, Adam, Mircea, Gougerot-Pocidalo, Marie-Anne, Cramer, Elisabeth M.
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - blood; Alkaline Phosphatase - deficiency; Azure Stains; Biological and medical sciences; Blood Platelet Disorders - blood; Blood Platelet Disorders - genetics; Blood Platelet Disorders - pathology; Blood Platelets - chemistry; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood Platelets - pathology; CD18 Antigens - analysis; Cell Lineage; Cell Size; Cells, Cultured; Child; Cytoplasmic Granules - chemistry; Cytoplasmic Granules - enzymology; Cytoplasmic Granules - metabolism; Diseases in Twins; Eosine Yellowish-(YS); Female; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - drug effects; Humans; Isoenzymes - blood; Isoenzymes - deficiency; Macrophage-1 Antigen - analysis; Medical sciences; Megakaryocytes - pathology; Microscopy, Immunoelectron; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophils - chemistry; Neutrophils - enzymology; Neutrophils - pathology; Platelet diseases and coagulopathies; Protein Transport; Receptors, Complement 3b - analysis; Staining and Labeling; Syndrome; Thrombopoietin - pharmacology; von Willebrand Factor - metabolism
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V98.5.1382

The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which thrombocytopenia is associated with increased platelet size and decreased α-granule content. This report describes 3 new pediatric cases presenting with the classical platelet abnormalities of GPS within one family with normal parents. Examination of blood smears of the 3 patients demonstrated not only gray platelets, but also gray polymorphonuclear neutrophils (PMNs) with decreased or abnormally distributed components of secretory compartments (alkaline phosphatase, CD35, CD11b/CD18). Secondary granules were also decreased in number as assayed by immunoelectron microscopy. These data confirm that the secretory compartments in neutrophils were also deficient in this family. Megakaryocytes (MKs) were cultured from the peripheral blood CD34+ cells of the 3 patients for 14 days, in the presence of thrombopoietin and processed for immunoelectron microscopy. Although von Willebrand factor (vWF) was virtually undetectable in platelets, vWF immunolabeling was conspicuous in cultured maturing MKs, particularly within Golgi saccules, but instead of being packaged in α-granules, it was released into the demarcation membrane system. In contrast, P-selectin followed a more classical 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 into the extracellular space instead of normal α-granule packaging. Furthermore, the secretory compartment of another blood cell line, the neutrophil, was also affected in this family of GPS.