Introduction:
Wiskott-Aldrich Syndrome (WAS) protein (WASp), encoded by WAS gene, is a multi-domain, adaptor protein that regulates actin-polymerization in the cytoplasm and RNA polymerase-II dependent transcription in hematoplymphoid cells1. WAS gene mutations have a broad range of phenotypic expressions usually grouped into three categories: Classical WAS, which manifest in immunodeficiency, autoimmunity, genomic instability, and cancer predisposition, X-linked neutropenia which present with neutropenia (XLN), and X-linked thrombocytopenia (XLT)2–4.
Clinical presentation of WAS can be atypical and may require a full panel of diagnostic immunologic and hematologic tests before making the correct diagnosis to provide optimal treatment 3,5. XLT, often misdiagnosed as Idiopathic thrombocytopenia (ITP), is a milder form of the disease associated with thrombocytopenia and small platelets. Microcytic thrombocytopenia is the hallmark of XLT leading to spontaneous and/or traumatic bleeding of varying severity6. In XLT patients, the incidence of malignancies is increased compared to general population but much lower than in classic WAS 3.
In the treatment of WAS and XLT a range of methods are employed based on the various phenotypic expressions from supportive care to more invasive options like splenectomy, hematopoietic stem cell transplant (HSCT), and gene therapy. Splenectomy can normalize platelet levels and sometimes correct mean platelet volume in XLT patients7. The use of thrombopoietin receptor agonists (TPO-RA) such as eltrombopag and romiplostim is approved for the treatment of ITP but has limited documented use in inherited thrombocytopenias8–11.
Eltrombopag is an oral non-peptide TPO-RA with excellent bioavailability capable of stimulating platelet production by stimulating platelet precursor differentiation through signaling JAK/STAT pathway9. Eltrombopag used in the management of ITP in pediatric patients shows an increase in platelet count and reduced bleeding12. Eltrombopag can also be administered indefinitely to WAS/XLT patients who respond, increasing platelet count and reducing bleeding while awaiting the development of a low-risk curative treatment13,14.