Anja J Gerrits1, Emily A Leven2, Andrew L Frelinger1, Sophie L Brigstocke2, Michelle A Berny-Lang1, W Beau Mitchell3, Shoshana Revel-Vilk4, Hannah Tamary5, Sabrina L Carmichael1, Marc R Barnard1, Alan D Michelson1, James B Bussel2. 1. Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 2. Division of Pediatric Hematology/Oncology, New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY; 3. 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; 4. Department of Pediatric Hematology/Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel; and. 5. Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
Abstract
UNLABELLED: 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.
UNLABELLED: 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/XLTpatients. In 9 WAS/XLTpatients 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/XLTpatients 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/XLTpatients was significantly less increased compared with 7 pediatric chronic immune thrombocytopenia (ITP) patients. Platelet activation did not improve in 3 WAS/XLTpatients 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/XLTpatients. This trial was registered at www.clinicaltrials.gov as #NCT00909363.
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