Faculty Opinions recommendation of A unique presentation of Wiskott-Aldrich syndrome in relation to platelet size.

2014 ◽  
Author(s):  
James Bussel
Keyword(s):  
Wiskott Aldrich Syndrome ◽  
Platelet Size

scholarly journals Platelet-associated immunoglobulin, platelet size, and the effect of splenectomy in the Wiskott-Aldrich syndrome

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1439-1443 ◽  
Author(s):  
L Corash ◽  
B Shafer ◽  
RM Blaese
Keyword(s):  
Platelet Count ◽  
Mean Platelet Volume ◽  
Critical Role ◽  
Volume Distribution ◽  
Normal Range ◽  
Platelet Volume ◽  
Wiskott Aldrich Syndrome ◽  
Platelet Size ◽  
Number Of Patients ◽  
Effect Of Splenectomy

Abstract Wiskott-Aldrich syndrome (WAS) thrombocytopenia is frequently improved by splenectomy, although the mechanism of the thrombocytopenia and its resolution are unknown. Previous studies in two patients have shown that mean platelet volume, which is characteristically reduced in WAS, increased along with platelet count postsplenectomy. Additional studies in a limited number of patients have also demonstrated that platelet- associated immunoglobulin G (PAIgG) is elevated presplenectomy, but to date no postsplenectomy data have been reported. The present study was performed to more fully evaluate the effect of splenectomy on platelet volume and PAIgG in WAS. Before splenectomy, mean platelet volume was reduced but platelet size was broadly distributed with substantial overlap of the normal range. PAIgG was significantly elevated in 13 of 14 presplenectomy WAS patients (means = 78.9 fg per platelet) and fell to normal levels postoperatively (means = 4.0 fg per platelet). Platelet count and clinical status improved postsplenectomy, and mean platelet volume and platelet volume distribution returned to the normal range. WAS subjects who relapsed with recurrent thrombocytopenia redeveloped elevated PAIgG but maintained normal platelet size. The spleen appears to play a critical role in a process that may be immunologically mediated and results in reduced platelet size.

scholarly journals Analysis of clinical and molecular genetic characteristics of Wiskott-Aldrich syndrome and X-linked thrombocytopenia

2021 ◽  
Vol 2 (3) ◽  
pp. 61-66
Author(s):  
Doina TURCAN ◽  
Lucia ANDRIES ◽  
Alexandr DORIF ◽  
Victoria SACARA
Keyword(s):  
Actin Polymerization ◽  
Wide Spectrum ◽  
Molecular Genetic ◽  
Clinical Findings ◽  
Recurrent Infections ◽  
Genetic Characteristics ◽  
Wiskott Aldrich Syndrome ◽  
Platelet Size ◽  
First Case ◽  
Small Platelet

Introduction. Wiskott-Aldrich syndrome is a rare X-linked disorder characterized by microthrombocytopenia, eczema, and recurrent infections. It is caused by mutations of the WAS gene which encodes the WAS protein (WASp) – a key regulator of actin polymerization in hematopoietic cells. Mutations within the WASp gene result in a wide heterogeneity of clinical disease, ranging from ‘classical WAS’ to mild asymptomatic thrombocytopenia (X-linked thrombocytopenia [XLT]), or congenital neutropenia (X-lined neutropenia [XLN]).Case presentation. This present paper reports a phenotypical and laboratory description of two children diagnosed with WAS and one child diagnosed with XLT. The first case was a six months old male with septicemia, thrombocytopenia, eczema and petechial rash. The second case was a 2 years old boy presenting with complaints of recurrent infections, eczema and thrombocytopenia with small platelet size. The third case was a 16 years old boy who presented with thrombocytopenia and recurrent sinopulmonary infections.Conclusions. Due to a wide spectrum of clinical findings, the diagnosis of WAS/XLT should be considered in any male patient presenting with petechiae, bruises, and congenital or early-onset thrombocytopenia associated with small platelet size.

scholarly journals Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia

Blood ◽  
2015 ◽  
Vol 126 (11) ◽  
pp. 1367-1378 ◽  
Author(s):  
Anja J. Gerrits ◽  
Emily A. Leven ◽  
Andrew L. Frelinger ◽  
Sophie L. Brigstocke ◽  
Michelle A. Berny-Lang ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Activation ◽  
Platelet Function ◽  
Syndrome X ◽  
Wiskott Aldrich Syndrome ◽  
Platelet Counts ◽  
Platelet Size ◽  
Key Points

Key Points Platelet function in WAS/XLT, measured by agonist-induced surface-activated GPIIb-IIIa and P-selectin, is proportional to platelet size. Eltrombopag increased platelet counts, but did not improve platelet activation, in most WAS/XLT patients.

Aberrant Microtubule Organization and Wiskott-Aldrich Syndrome-like Defects in Platelets and Megakaryocytes of Profilin1-Deficient Mice

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4200-4200
Author(s):  
Simon Stritt ◽  
Markus Bender ◽  
Paquita Nurden ◽  
Judith van Eeuwijk ◽  
Barbara Zieger ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Trichostatin A ◽  
Microtubule Organization ◽  
Interacting Protein ◽  
Wiskott Aldrich Syndrome ◽  
Microtubule Stability ◽  
Platelet Size ◽  
Deacetylase Inhibitor ◽  
Histone Deacetylase Inhibitor Trichostatin ◽  
Deficient Mice

Abstract Wiskott-Aldrich syndrome (WAS) is a rare, X-chromosomal recessive disorder which is caused by mutations in the WAS gene and characterized by eczema, immunodeficiency and microthrombocytopenia (Thrasher and Burns, Nat Rev Immunol 2010). Interestingly, WAS protein (WASp)-deficient mice have normal-sized platelets and thus the molecular link between WAS mutations and its central hallmark microthrombocytopenia remains elusive. Profilin1 (Pfn1) is a key actin-regulating protein that, besides actin, interacts with phosphoinositides and multiple proline-rich proteins including the WAS protein (WASp)/WASp-interacting protein (WIP) complex (Witke, Trends Cell Biol 2004; Ramesh et al., Proc Natl Acad Sci USA, 1997). Interestingly, similar to WAS patients, mice with Pfn1-null megakaryocytes/platelets suffered from microthrombocytopenia. We identified accelerated platelet clearance by macrophages and pre-mature platelet release into the bone marrow compartment as the major cause of the reduced platelet count in Pfn1-deficient mice. Both, platelets from Pfn1-null mice and WAS patients contained abnormally organized and hyperstable microtubules. We next tested, if increased microtubule stability could account for the reduced size of Pfn1-deficient platelets. Treatment of control platelets with microtubule stabilizing toxins, such as the histone-deacetylase inhibitor trichostatin A (TSA) or taxol resulted in a decreased platelet size. This finding indicates that increased microtubule stability could account for the reduced platelet size in Pfn1-deficient mice but also in WAS patients. Based on these results we speculate that WASp might modulate Pfn1 function and dysregulation of this interaction leads to increased stability and altered organization of microtubules. In support of this, the subcellular localization of Pfn1 was altered in platelets of three WAS patients. Together, these results reveal an unexpected function of Pfn1 as a regulator of microtubule organization and point to a previously unrecognized mechanism underlying the platelet formation defect in WAS patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals A rare case of Wiskott-Aldrich Syndrome with normal platelet size: a case report

2016 ◽  
Vol 10 (1) ◽  
Author(s):  
Mohd Farid Baharin ◽  
Jasbir Singh Dhaliwal ◽  
Smrdhi V. V. Sarachandran ◽  
Siti Zaharah Idris ◽  
Seoh Leng Yeoh
Keyword(s):  
Case Report ◽  
Rare Case ◽  
Wiskott Aldrich Syndrome ◽  
Normal Platelet ◽  
Platelet Size

A unique presentation of Wiskott-Aldrich syndrome in relation to platelet size

2011 ◽  
Vol 56 (7) ◽  
pp. 1127-1129 ◽  
Author(s):  
Payal D. Patel ◽  
Joy M. Samanich ◽  
William B. Mitchell ◽  
Deepa Manwani
Keyword(s):  
Wiskott Aldrich Syndrome ◽  
Platelet Size

The Thrombocytopenia of Wiskott Aldrich Syndrome Is Not Related to a Defect in Proplatelet Formation

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 509-518 ◽  
Author(s):  
Elie Haddad ◽  
Elisabeth Cramer ◽  
Christel Rivière ◽  
Philippe Rameau ◽  
Fawzia Louache ◽  
...  
Keyword(s):  
Blood Platelets ◽  
Critical Role ◽  
Consistent Finding ◽  
Cytoskeletal Organization ◽  
Platelet Production ◽  
Wiskott Aldrich Syndrome ◽  
Platelet Size ◽  
Proplatelet Formation ◽  
Small Platelet

Abstract The Wiskott-Aldrich syndrome (WAS) is an X-linked hereditary disease characterized by thrombocytopenia with small platelet size, eczema, and increased susceptibility to infections. The gene responsible for WAS was recently cloned. Although the precise function of WAS protein (WASP) is unknown, it appears to play a critical role in the regulation of cytoskeletal organization. The platelet defect, resulting in thombocytopenia and small platelet size, is a consistent finding in patients with mutations in the WASP gene. However, its exact mechanism is unknown. Regarding WASP function in cytoskeletal organization, we investigated whether these platelet abnormalities could be due to a defect in proplatelet formation or in megakaryocyte (MK) migration. CD34+ cells were isolated from blood and/or marrow of 14 WAS patients and five patients with hereditary X-linked thrombocytopenia (XLT) and cultured in serum-free liquid medium containing recombinant human Mpl-L (PEG-rHuMGDF) and stem-cell factor (SCF) to study in vitro megakaryocytopoiesis. In all cases, under an inverted microscope, normal MK differentiation and proplatelet formation were observed. At the ultrastructural level, there was also no abnormality in MK maturation, and normal filamentous MK were present. Moreover, the in vitro produced platelets had a normal size, while peripheral blood platelets of the same patients exhibited an abnormally small size. However, despite this normal platelet production, we observed that F-actin distribution was abnormal in MKs from WAS patients. Indeed, F-actin was regularly and linearly distributed under the cytoplasmic membrane in normal MKs, but it was found concentrated in the center of the WAS MKs. After adhesion, normal MKs extended very long filopodia in which WASP could be detected. In contrast, MKs from WAS patients showed shorter and less numerous filopodia. However, despite this abnormal filopodia formation, MKs from WAS patients normally migrated in response to stroma-derived factor-1 (SDF-1), and actin normally polymerized after SDF-1 or thrombin stimulation. These results suggest that the platelet defect in WAS patients is not due to abnormal platelet production, but instead to cytoskeletal changes occuring in platelets during circulation.

scholarly journals 804 PLATELET ASSOCIATED IMMUNOGLOBULIN, PLATELET SIZE AND THE EFFECT OF SPLENECTOMY IN THE WISKOTT-ALDRICH SYNDROME

1981 ◽  
Vol 15 ◽  
pp. 576-576 ◽  
Author(s):  
Laurence Corash ◽  
Brenda Shafer ◽  
Wendell Rosse ◽  
B Hiohael Blaeae
Keyword(s):  
Wiskott Aldrich Syndrome ◽  
Platelet Size ◽  
Effect Of Splenectomy

The Thrombocytopenia of Wiskott Aldrich Syndrome Is Not Related to a Defect in Proplatelet Formation

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 509-518 ◽  
Author(s):  
Elie Haddad ◽  
Elisabeth Cramer ◽  
Christel Rivière ◽  
Philippe Rameau ◽  
Fawzia Louache ◽  
...  
Keyword(s):  
Blood Platelets ◽  
Critical Role ◽  
Consistent Finding ◽  
Cytoskeletal Organization ◽  
Platelet Production ◽  
Wiskott Aldrich Syndrome ◽  
Platelet Size ◽  
Proplatelet Formation ◽  
Small Platelet

The Wiskott-Aldrich syndrome (WAS) is an X-linked hereditary disease characterized by thrombocytopenia with small platelet size, eczema, and increased susceptibility to infections. The gene responsible for WAS was recently cloned. Although the precise function of WAS protein (WASP) is unknown, it appears to play a critical role in the regulation of cytoskeletal organization. The platelet defect, resulting in thombocytopenia and small platelet size, is a consistent finding in patients with mutations in the WASP gene. However, its exact mechanism is unknown. Regarding WASP function in cytoskeletal organization, we investigated whether these platelet abnormalities could be due to a defect in proplatelet formation or in megakaryocyte (MK) migration. CD34+ cells were isolated from blood and/or marrow of 14 WAS patients and five patients with hereditary X-linked thrombocytopenia (XLT) and cultured in serum-free liquid medium containing recombinant human Mpl-L (PEG-rHuMGDF) and stem-cell factor (SCF) to study in vitro megakaryocytopoiesis. In all cases, under an inverted microscope, normal MK differentiation and proplatelet formation were observed. At the ultrastructural level, there was also no abnormality in MK maturation, and normal filamentous MK were present. Moreover, the in vitro produced platelets had a normal size, while peripheral blood platelets of the same patients exhibited an abnormally small size. However, despite this normal platelet production, we observed that F-actin distribution was abnormal in MKs from WAS patients. Indeed, F-actin was regularly and linearly distributed under the cytoplasmic membrane in normal MKs, but it was found concentrated in the center of the WAS MKs. After adhesion, normal MKs extended very long filopodia in which WASP could be detected. In contrast, MKs from WAS patients showed shorter and less numerous filopodia. However, despite this abnormal filopodia formation, MKs from WAS patients normally migrated in response to stroma-derived factor-1 (SDF-1), and actin normally polymerized after SDF-1 or thrombin stimulation. These results suggest that the platelet defect in WAS patients is not due to abnormal platelet production, but instead to cytoskeletal changes occuring in platelets during circulation.

Microparticles And Reticulated Platelets In Wiskott-Aldrich Syndrome Patients

2000 ◽  
Vol 109 (3) ◽  
pp. 673-673 ◽  
Author(s):  
A. Matzdorff ◽  
B. Kemkes-Matthes ◽  
H. Pralle
Keyword(s):  
Wiskott Aldrich Syndrome ◽  
Reticulated Platelets
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