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.