title: Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia.
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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Anja J
authors.initials: AJ
authors.lastname: Gerrits
authors.affiliation: Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY;
authors.forename: Emily A
authors.initials: EA
authors.lastname: Leven
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Frelinger
authors.affiliation: Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY;
authors.forename: Sophie L
authors.initials: SL
authors.lastname: Brigstocke
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Berny-Lang
authors.affiliation: Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY; Platelet Biology Laboratory, New York Blood Center, New York, NY;
authors.forename: W Beau
authors.initials: WB
authors.lastname: Mitchell
authors.affiliation: Department of Pediatric Hematology/Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel; and.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Revel-Vilk
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Sabrina L
authors.initials: SL
authors.lastname: Carmichael
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Marc R
authors.initials: MR
authors.lastname: Barnard
authors.affiliation: Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
authors.forename: Alan D
authors.initials: AD
authors.lastname: Michelson
authors.affiliation: Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY;
authors.forename: James B
authors.initials: JB
authors.lastname: Bussel
mesh_terms: D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D040181:Genetic Diseases, X-Linked / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D006834:Hydrazines / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D063847:Mean Platelet Volume; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists; D013921:Thrombocytopenia / Q000097:blood* / Q000188:drug therapy*; D014923:Wiskott-Aldrich Syndrome / Q000097:blood* / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C520809:eltrombopag