Roles of circulating cell-derived Microparticles on hematopoietic stem cell transplantation and hypercoagulable state in thalassemia

Abstract

β-Thalassemia major is a chronic haemolytic anemia as a result of decreased β-globin synthesis. Hematopoietic stem cell transplantation or bone marrow transplantation (BMT) serves as the only cure for these patients. One interesting complication in β-thalassemia is chronic hypercoagulable state resulted from many contributing factors, such as increases of activated platelets, microparticles (MPs) bearing phosphatidylserine (PS), microaggreagtion of leukocyte-platelet, endothelial cell activation etc. However, the association between these factors regarding the cause of prothrombotic state are incompletely understood. In this study, the determination of aforementioned factors in young patients undergone BMT were carried out by flow cytometry in a cross-sectional cohort. These parameters including red cells expressing PS and activated platelets were decreased in BMT groups compared to patients receiving regular transfusion while MPs derived from platelets, leukocyte and endothelial cells were increased. The different patterns of leukocyte-platelet aggregation were found. In addition, long-term study of these factors was monitored during the course of BMT. Moreover, the effects of thalassemic MPs on promoting leukocyte-platelet aggregation and endothelial cell activation were explored in comparison to MPs from normal subjects. Both MPs prepared from healthy adult donors or β-thalassemia patients were capable of enhancing leukocyte-platelet aggregation, activating leukocytes, inducing endothelial cell activation and proinflammatory responses. In summary, BMT can correct, in part, prothrombophilic phenotype by reducing PS-exposing RBCs and activated platelets but not PS-bearing MPs. Besides, the functional studies of MPs were also investigated, which suggest the roles of MPs in thromboembolic events in β-thalassemia patients.