Evolution of Platelet Function and Bleeding in Children and Adults with Chronic Immune Trombocytopenia on Romiplostim Treatment

INTRODUCTION. Platelets in immune thrombocytopenia (ITP) are not only reduced in quantity, but were also reported to have impaired function. There is evidence that this might be the mechanism behind the clinically established fact that severity of bleeding in ITP does not correllate well with the degree of thrombocytopenia. However, there are no established methods or guidelines to predict bleeding risks based on the platelet function tests, and little information about the effects of thrombopoietin mimetics on platelet function. MATERIALS. We studied evolution of platelet function and clinical bleeding symptoms in 32 adult and 44 pediatric patients with chronic ITP 32 over six months of romiplostim treatment using flow cytometry and thrombelastography (TEG). As controls, samples of 20 healthy donors were used. The median age of adult patients was 62 (19-80 years), that of pediatric patients was 10 (1-18 years). All had previous history of treatment (one to three lines of therapy). Platelet function was characterized by flow cytometry before and after activation with SFLLRN plus collagen-related peptide. Levels of CD42b, CD61, CD62P, PAC1, annexin V binding, and mepacrine uptake and release were evaluated. Bleeding score was determined using a standardized consensus-based ITP-specific bleeding assessment tool developed by the International Working Group on ITP. Thrombelastography (TEG) was employed to characterize integral hemostasis function. Investigations were performed in accordance with the Declaration of Helsinki under a protocol approved by the NSPC CHOI Ethical Committee, and written informed consent was obtained from all donors and patients. Comparisons between groups were performed using Mann-Whitney non-parametric test. RESULTS. Bleeding before the start of therapy was observed in 10 adults and 25 children. There was no significant difference in platelet count between the bleeding and non-bleeding adults (median 25 versus 23, respectively). For children, it was significantly (median 19 versus 83, p CONCLUSIONS. Our data indicate that: a) platelets in chronic ITP are pre-activated, large and slowly reacting; b) these changes are associated with bleeding independently of platelet count, and can be used for risk stratification; c) romiplostim treatment decreases platelet size and pre-activation. Disclosures Panteleev: Amgen: Research Funding.