Eltrombopag use in a patient with Wiskott–Aldrich syndrome

Abstract

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.

Inherited thrombocytopenias: history, advances and perspectives

“… 144 Thrombopoietin-mimetics have more recently been used for a patient with a DIAPH1 mutation prior to hip arthroplasty and as a “bridge” for a child with WAS and severe thrombocytopenia awaiting HSC transplantation. 145 , 146 The goal in such situations is to transiently increase the platelet count to >50×10 9 platelets/L. Romiplostim has been successful in correcting the platelet count resulting from mutations in THPO in congenital amegakaryocytic thrombocytopenia in which the patient’s own thrombopoietin is absent or non-functional.…”

Thrombopoietin receptor agonists in hereditary thrombocytopenias

“…• Clinical study with eltrombopag (n = 8): after 22-209 weeks of treatment, spontaneous bleeding was reduced in 75% of patients [34] • Case study with eltrombopag: one patient achieved a stable platelet count and remission of bleeding symptoms [35] • Clinical trial with eltrombopag ongoing [42] Although there is no evidence of an increased risk of lymphoid malignancies with TPO-RAs, careful monitoring is recommended Potential effects of long-term eltrombopag exposure on the success rate of transplant engraftment after HSCT have not been studied…”

“…Among the three patients who did not meet the response criteria, one continued eltrombopag because of a small reduction in bleeding symptoms combined with the lack of a better alternative, and two patients discontinued: one of them switched to romiplostim and experienced an increase in the platelet count (> 20 × 10 9 L –1 ) and decreased bleeding . A recent case study reported that another patient with WAS, who had severe thrombocytopenia and bleeding, was treated with eltrombopag and achieved a stable increase in the platelet count and remission of bleeding symptoms .…”

Platelets in Wiskott-Aldrich syndrome: Victims or executioners?

“…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 …”

“…66 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. 70,71 The gold standard of treatment is HSCT, 72 however, this treatment is available only in a minority of patients. In general, PLT counts increase after transplantation, both in patients who underwent splenectomy and those who did not, and is dependent on the degree of myeloid chimerism.…”