Abstract
BackgroundProlonged isolated thrombocytopenia (PT) is a frequent complication in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it is associated with an adverse prognosis. In this study, we hypothesized that desialylation on platelet surfaces was associated with PT after allo-HSCT. The mechanisms participating in this process may include NEU1 translocation, platelet apoptosis, and phagocytosis by macrophages.MethodsPT was defined as a peripheral platelet count less than 100 × 109/L without sustained anemia or leukopenia for more than 3 months after allo-HSCT. 34 patients were identified consecutively from a cohort of 255 patients who underwent allo-HSCT for hematologic malignancies between May and October 2014 at Peking University Institute of Hematology. Desialylation, enzyme expression, and phagocytosis were detected using flow cytometry, immunofluorescence, RT-PCR, Western blot, and so on.ResultsPlatelets from the PT patients had significantly fewer sialic acids (P = .001) and increased β-galactose exposure indicative of desialylation on the surface (P = .042), and serum from the PT patients showed a higher sialic acid concentration (8.400 ± 0.2209 μmol/L, P < .001). The sialidase NEU1 was over-expressed from mRNA to protein levels, and its catalytic activity was increased in platelets from the PT patients. Desialylation of GPIbα in the PT patients was correlated with changes in 14-3-3ζ distribution, which, relative to Bad activation, modulated the expression of Bcl-2 family proteins, depolarized the inner membrane of the mitochondria, and initiated the intrinsic mitochondria-dependent pathway of apoptosis. Macrophages derived from the THP-1 cell line preferred to phagocytize desialylated platelets from the PT patients in vitro. We also revealed that oseltamivir (400 μmol/L) could inhibit 50 % of the sialidase activity on platelets and could protect 20 % of platelets from phagocytosis in vitro.ConclusionsDesialylation of platelets was associated with platelet apoptosis and phagocytosis, whereas oseltamivir could reduce platelet destruction in the periphery, indicating a potential novel treatment for PT after allo-HSCT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0216-3) contains supplementary material, which is available to authorized users.
Highlights
Prolonged isolated thrombocytopenia (PT), which is defined as a consistently low platelet count for more than 3 months after transplantation despite the recovery of all other peripheral blood cell lines, is a frequent complication of allogeneic hematopoietic stem cell transplantation, with an incidence of 5–37 % [1,2,3,4]
Our previous study found that cellular elements in the bone marrow microenvironment, including endothelial cells and perivascular cells, were significantly reduced in PT patients, indicating that an impaired bone marrow vascular microenvironment might contribute to the occurrence of PT [9]
We demonstrate that the platelet surfaces were desialylated by NEU1 in PT patients, which was associated with platelet apoptosis and phagocytosis by macrophages in the pathogenesis of PT
Summary
Prolonged isolated thrombocytopenia (PT), which is defined as a consistently low platelet count for more than 3 months after transplantation despite the recovery of all other peripheral blood cell lines, is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with an incidence of 5–37 % [1,2,3,4]. Our previous study found that cellular elements in the bone marrow microenvironment, including endothelial cells and perivascular cells, were significantly reduced in PT patients, indicating that an impaired bone marrow vascular microenvironment might contribute to the occurrence of PT [9] Another of our studies showed that increased CD8+/CX3CR1+ T cells in the bone marrow might be associated with PT [11]. Enlarged MPV can be used as a measurement of young platelets, indicating that the origin of thrombocytopenia was peripheral destruction [13] Other laboratory methods, such as plasma glycocalicin index (GCI), have been reported to be useful for the diagnosis of thrombocytopenia. Desialylation, enzyme expression, and phagocytosis were detected using flow cytometry, immunofluorescence, RT-PCR, Western blot, and so on
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
