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

Gerrits, Anja J.; Leven, Emily; Frelinger, Andrew L.; Brigstocke, Sophie L.; Berny‐Lang, Michelle A.; Mitchell, W. Beau; Revel‐Vilk, Shoshana; Tamary, Hannah; Carmichael, Sabrina L.; Barnard, Marc R.; Michelson, Alan D.; Bussel, James B.

doi:10.1182/blood-2014-09-602573

Cited by 88 publications

(80 citation statements)

References 48 publications

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“…43,44 One study of eltrombopag in WiskottAldrich syndrome or X-linked thrombocytopenia showed improved platelet counts but persistent defects in platelet activation. 45 Although eltrombopag has been approved for use as a therapy for refractory chronic ITP in children, the authors of this study have used eltrombopag to treat severe, refractory bleeding in patients with acute ITP at the time of presentation. In this setting, eltrombopag was given to help sustain an elevated platelet count while other first-line agents were given for more immediate effect.…”

Section: Other Indications and Future Directionsmentioning

confidence: 99%

Eltrombopag for use in children with immune thrombocytopenia

2018

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Eltrombopag is currently the only US Food and Drug Administration–approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects. The most commonly reported drug-related adverse effects include headache, nausea, and hepatobiliary laboratory abnormalities. Long-term safety data in children are limited, and studies in adults have not revealed a clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation. Eltrombopag has also been approved for treating refractory severe aplastic anemia (AA) and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.

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Section: Other Indications and Future Directionsmentioning

confidence: 99%

Eltrombopag for use in children with immune thrombocytopenia

2018

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“…Recently, new thrombopoietin agonists, such as romiplostim (Nplate; Amgen, Thousand Oaks, CA, USA) and eltrombopag (Revolade; GlaxoSmithKline, Brentford, UK), have been used to treat thrombocytopenia to prevent life‐threatening bleeding while patients wait for HSCT . In particular, eltrombopag has been tested in a clinical trial (NCT00909363) in patients with WAS and XLT that reported an increase in PLT counts in the majority of patients …”

Section: Wasmentioning

confidence: 99%

Platelets in Wiskott-Aldrich syndrome: Victims or executioners?

Sereni

Castiello

Villa

2017

Journal of Leukocyte Biology

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Microthrombocytopenia is the clinical hallmark of WAS, a rare X-linked immunodeficiency that is characterized by eczema, autoimmunity, and cancer susceptibility. This disease is caused by mutations in the WAS gene, which is expressed in hematopoietic cells and regulates actin cytoskeleton remodeling thereby modulating various cellular functions, including motility, immunologic synapse assembly, and signaling. Despite extensive studies that have provided great insight into the relevance of this molecule to innate and cellular immunity, the exact mechanisms of microthrombocytopenia in WAS are still unknown. This review focuses on the recent progress made in dissecting the pathogenesis of platelet defects in patients with WAS and their murine counterparts. In parallel, we will provide an overview of the state-of-the art platelets as immune modulators at the interface between hemostasis and the immune system, which suggests that these cells may have a direct role in the pathogenesis of immune dysregulation in WAS.

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“…Here we report the successful use of eltrombopag in a patient with WAS: this treatment reduced bleeding symptoms and completely eliminated the requirement for platelet transfusion. Our case adds to the literature suggesting the efficacy of eltrombopag in patients with WAS as a measure to manage profound thrombocytopenia and recurrent bleeding while awaiting definitive treatment . In particular, it may be suitable for children under the age of 2 years for whom bleeding is the first severe manifestation of WAS and may be fatal .…”

Section: Discussionmentioning

confidence: 81%

“…However, splenectomy increases the risk of severe infections, particularly after HSCT, and platelet transfusions are short‐lived, may lead to allo‐immunization, and may not be effective in all patients . Eltrombopag, a thrombopoietin (TPO) receptor agonist, is a new efficient treatment for immune thrombocytopenia in both adults and children and has been proposed also for patients with inherited thrombocytopenia . In particular, in patients with WAS, platelet production is impaired as the defective protein is essential for the polymerization of actin and proplatelets formation .…”

Section: Introductionmentioning

confidence: 99%

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Eltrombopag use in a patient with Wiskott–Aldrich syndrome

Gabelli

Antonio

Notarangelo

et al. 2017

Pediatric Blood & Cancer

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Wiskott-Aldrich syndrome (WAS) is an inherited X-linked disorder characterized by microthrombocytopenia, immunodeficiency, and eczema. Hematopoietic stem cell transplantation (HSCT) is the treatment of choice. Eltrombopag, a thrombopoietin receptor agonist, may be useful to prevent bleeding while awaiting HSCT. We present a case of a male with WAS, profound thrombocytopenia, and bleeding diathesis successfully managed with eltrombopag before HSCT. Eltrombopag was given for 32 weeks obtaining a stable platelet count without any platelet transfusion. The patient did not experience any bleeding symptom. Eltrombopag may be a suitable therapeutic option for patients with WAS and severe thrombocytopenia as "bridge" to definitive cure.

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

Abstract: 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.

Cited by 88 publications

References 48 publications

Eltrombopag for use in children with immune thrombocytopenia

Eltrombopag for use in children with immune thrombocytopenia

Platelets in Wiskott-Aldrich syndrome: Victims or executioners?

Eltrombopag use in a patient with Wiskott–Aldrich syndrome

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