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.