Conclusions and Discussion:
The most commonly occurring clinical presentation of XLT is spontaneous and trauma-induced bleeding episodes. Managing bleeding episodes in is the goal of therapeutic options employed such as TPO- RAs until there is a definitive treatment becomes available. HSCT is considered largely curative in classical WAS as it provides a cure for all aspects of the disease contingent on whether hematologic and immune reconstitution is achieved 5. However, the use of HSCT for XLT is still controversial, given the excellent long-term survival observed with medical management.
Eltrombopag use to increase platelet count in the pediatric population has been employed successfully in chronic ITP, severe aplastic anemia, and chronic hepatitis C infection9. Case reports of eltrombopag induced increase in platelet counts have been published in WAS10,16 and in XLT10,17. One case of clinical response without numerical response was included in one report10.
The known mechanism of action of Eltrombopag is to bind to a transmembrane portion of the TPO receptor, stimulating Megakaryocyte (MK) precursor cells and MK differentiation leading to an increase in platelet counts18. A systematic review of TPO-RA activity has also shown Eltrombopag appears to alter platelet activation, concerning levels of platelet-monocyte aggregates, soluble P-selectin, as well as possibly GPVI expression, and adhesion under flow19,20. However, Gerritts et al found no evidence of changes in agonist induced platelet activation by etrombopag10.
Our report provides additional data for utilization of TPO-RAs in bleeding. The clinical improvement of this patient despite reduced platelet count over the 2-year course of treatment with eltrombopag suggests possible involvement of mechanisms other than an increase in platelet counts although an increased utilization of platelets at site of injury is also possible.
We conclude that TPO-RA may be effective even in the absence of a platelet number response and should considered in symptomatic management of XLT patients, and possibly other inherited thrombocytopenia cases.