Flow cytometric analysis of platelets from children with the Wiskott- Aldrich syndrome reveals defects in platelet development, activation and structure
(1997) In British Journal of Haematology 97(4). p.747-754- 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... (More)
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.
(Less)
- author
- Semple, John W. LU ; Siminovitch, Katherine A. ; Mody, Meera ; Milev, Youli ; Lazarus, Alan H. ; Wright, J. Fraser and Freedman, John
- publishing date
- 1997-01-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Activation studies, Flow cytometry, Platelet glycoproteins, Platelets, Wiskott-Aldrich syndrome
- in
- British Journal of Haematology
- volume
- 97
- issue
- 4
- pages
- 8 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:9217172
- scopus:0030824870
- ISSN
- 0007-1048
- DOI
- 10.1046/j.1365-2141.1997.1132938.x
- language
- English
- LU publication?
- no
- id
- 01230a7d-1410-4297-9c6b-5f4dea599e45
- date added to LUP
- 2019-12-03 10:30:06
- date last changed
- 2024-01-16 16:37:41
@article{01230a7d-1410-4297-9c6b-5f4dea599e45,
abstract = {{<p>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.</p>}},
author = {{Semple, John W. and Siminovitch, Katherine A. and Mody, Meera and Milev, Youli and Lazarus, Alan H. and Wright, J. Fraser and Freedman, John}},
issn = {{0007-1048}},
keywords = {{Activation studies; Flow cytometry; Platelet glycoproteins; Platelets; Wiskott-Aldrich syndrome}},
language = {{eng}},
month = {{01}},
number = {{4}},
pages = {{747--754}},
publisher = {{Wiley-Blackwell}},
series = {{British Journal of Haematology}},
title = {{Flow cytometric analysis of platelets from children with the Wiskott- Aldrich syndrome reveals defects in platelet development, activation and structure}},
url = {{http://dx.doi.org/10.1046/j.1365-2141.1997.1132938.x}},
doi = {{10.1046/j.1365-2141.1997.1132938.x}},
volume = {{97}},
year = {{1997}},
}