title: Flow cytometric analysis of platelets from children with the Wiskott-Aldrich syndrome reveals defects in platelet development, activation and structure.
abstract: The pathophysiology of platelet dysfunction in the Wiskott-Aldrich immune deficiency syndrome (WAS) remains unclear. Using flow cytometry, we have characterized the functional properties of platelets from 10 children with WAS. Patients with WAS had thrombocytopenia, small platelets, increased platelet-associated IgG and reduced platelet-dense granule content. Levels of reticulated 'young' platelets were normal in the WAS patients. Although the mean numbers of platelet glycoprotein (GP) Ib, GPIIbIIIa and GPIV molecules per platelet appeared lower in WAS patients than in healthy controls, analysis of similar-sized platelets revealed the mean number of GPIb molecules per platelet to be comparable in patients and normal controls. Surface GPIIbIIIa and GPIV expression was, however, significantly lower on the WAS platelets than on normal platelets. Compared with normal platelets, WAS platelets showed a reduced ability to modulate GPIIbIIIa expression following thrombin stimulation. In addition, thrombin- and ADP-induced expression of CD62P and CD63 was defective in WAS platelets. Phallacidin staining of the WAS platelets revealed less F-actin content than in normal platelets. Together, these data suggest that the reduced platelet number and function in WAS reflects, at least in part, a defect in bone marrow production as well as an intrinsic platelet abnormality.
authors.affiliation: Division of Hematology, St Michael's Hospital, and The Toronto Platelet Immunology Group, Ontario, Canada.
authors.forename: J W
authors.initials: JW
authors.lastname: Semple
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: M
authors.initials: M
authors.lastname: Mody
authors.forename: Y
authors.initials: Y
authors.lastname: Milev
authors.forename: A H
authors.initials: AH
authors.lastname: Lazarus
authors.forename: J F
authors.initials: JF
authors.lastname: Wright
authors.forename: J
authors.initials: J
authors.lastname: Freedman
mesh_terms: D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism; D002675:Child, Preschool; D006801:Humans; D019007:P-Selectin / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D013194:Staining and Labeling; D060149:Tetraspanin 30; D014923:Wiskott-Aldrich Syndrome / Q000097:blood*
chemical_list: D000199:Actins; D015703:Antigens, CD; D018955:CD36 Antigens; C554586:CD63 protein, human; D019007:P-Selectin; D010456:Peptides, Cyclic; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; C017613:phallacidin