Abstract The pathogenesis of childhood chronic immune thrombocytopenic purpura (ITP) is mainly mediated by antiplatelet autoantibodies, which have been shown to induce platelet apoptosis in murine models. Decreased CXCR4 expression, which can regulate apoptotic pathway, has been described in platelet disorders. The present study aims to determine whether platelet apoptosis is increased in pediatric patients with chronic ITP and whether there is any involvement of the CXCR4 chemokines axis. Twenty-one patients and 12 controls were studied. Using flow cytometry, we investigated apoptotic markers of platelets including annexin V, caspase 3, and mitochondrial inner transmembrane potential depolarization. The percentage of the platelets with apoptosis-positive markers was not increased in chronic ITP patients. CXCR4 expression was higher in the patients as detected by flow cytometric ( P = 0.001) and western blotting analysis ( P = 0.013). The results also revealed that CXCR4 downstream proteins, Akt phosphorylation was more frequent in chronic ITP patients than controls. Plasma stromal cell-derived factor 1 levels analyzed by enzyme-linked immunosorbent assay were decreased in patients ( P = 0.001) and inversely correlated to CXCR4 expression ( r = -0.62, P < 0.001). In conclusion, the study shows platelet apoptosis resistance existing in pediatric patients with chronic ITP. It may be associated with enhanced CXCR4 expression and Akt activation.