title: Newly recognized cellular abnormalities in the gray platelet syndrome.
abstract: The gray platelet syndrome (GPS) is a rare congenital bleeding disorder in which thrombocytopenia is associated with increased platelet size and decreased alpha-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 alpha-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 alpha-granule packaging. Furthermore, the secretory compartment of another blood cell line, the neutrophil, was also affected in this family of GPS.
authors.affiliation: INSERM U. 474, Hôpital de Port-Royal, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Drouin
authors.forename: R
authors.initials: R
authors.lastname: Favier
authors.forename: J M
authors.initials: JM
authors.lastname: Massé
authors.forename: N
authors.initials: N
authors.lastname: Debili
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.forename: C
authors.initials: C
authors.lastname: Elbim
authors.forename: J
authors.initials: J
authors.lastname: Guichard
authors.forename: M
authors.initials: M
authors.lastname: Adam
authors.forename: M A
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.forename: E M
authors.initials: EM
authors.lastname: Cramer
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood / Q000172:deficiency; D001399:Azure Stains; D001791:Blood Platelet Disorders / Q000097:blood / Q000235:genetics / Q000473:pathology*; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018821:CD18 Antigens / Q000032:analysis; D019070:Cell Lineage; D048429:Cell Size; D002478:Cells, Cultured; D002648:Child; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D004200:Diseases in Twins; D004801:Eosine Yellowish-(YS); D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000172:deficiency; D016177:Macrophage-1 Antigen / Q000032:analysis; D008533:Megakaryocytes / Q000473:pathology; D016253:Microscopy, Immunoelectron; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D021381:Protein Transport; D017463:Receptors, Complement 3b / Q000032:analysis; D013194:Staining and Labeling; D013577:Syndrome; D013926:Thrombopoietin / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001399:Azure Stains; D018821:CD18 Antigens; D007527:Isoenzymes; D016177:Macrophage-1 Antigen; D017463:Receptors, Complement 3b; C046541:Romanowsky-Giemsa stain; D014841:von Willebrand Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013926:Thrombopoietin; D000469:Alkaline Phosphatase; D004801:Eosine Yellowish-(YS)