Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia

Blood. 2015 Sep 10;126(11):1367-78. doi: 10.1182/blood-2014-09-602573. Epub 2015 Jul 29.

Abstract

Because Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) patients have microthrombocytopenia, hemorrhage is a major problem. We asked whether eltrombopag, a thrombopoietic agent, would increase platelet counts, improve platelet activation, and/or reduce bleeding in WAS/XLT patients. In 9 WAS/XLT patients and 8 age-matched healthy controls, platelet activation was assessed by whole blood flow cytometry. Agonist-induced platelet surface activated glycoprotein (GP) IIb-IIIa and P-selectin in WAS/XLT patients were proportional to platelet size and therefore decreased compared with controls. In contrast, annexin V binding showed no differences between WAS/XLT and controls. Eltrombopag treatment resulted in an increased platelet count in 5 out of 8 patients. Among responders to eltrombopag, immature platelet fraction in 3 WAS/XLT patients was significantly less increased compared with 7 pediatric chronic immune thrombocytopenia (ITP) patients. Platelet activation did not improve in 3 WAS/XLT patients whose platelet count improved on eltrombopag.

In conclusion: (1) the reduced platelet activation observed in WAS/XLT is primarily due to the microthrombocytopenia; and (2) although the eltrombopag-induced increase in platelet production in WAS/XLT is less than in ITP, eltrombopag has beneficial effects on platelet count but not platelet activation in the majority of WAS/XLT patients. This trial was registered at www.clinicaltrials.gov as #NCT00909363.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Benzoates / therapeutic use*
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Genetic Diseases, X-Linked / blood*
  • Genetic Diseases, X-Linked / drug therapy*
  • Humans
  • Hydrazines / therapeutic use*
  • Infant
  • Male
  • Mean Platelet Volume
  • P-Selectin / blood
  • Platelet Activation / drug effects
  • Platelet Count
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Pyrazoles / therapeutic use*
  • Receptors, Thrombopoietin / agonists
  • Thrombocytopenia / blood*
  • Thrombocytopenia / drug therapy*
  • Wiskott-Aldrich Syndrome / blood*
  • Wiskott-Aldrich Syndrome / drug therapy*
  • Young Adult

Substances

  • Benzoates
  • Hydrazines
  • P-Selectin
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Pyrazoles
  • Receptors, Thrombopoietin
  • MPL protein, human
  • eltrombopag

Supplementary concepts

  • Thrombocytopenia 1

Associated data

  • ClinicalTrials.gov/NCT00909363