Multiple concomitant mechanisms contribute to low platelet count in patients with immune thrombocytopenia.

Autor: Grodzielski M; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina., Goette NP; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina., Glembotsky AC; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina., Constanza Baroni Pietto M; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina., Méndez-Huergo SP; Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME), National Scientific Council of Scientific and Technical Research (CONICET), C1428, Buenos Aires, Argentina., Pierdominici MS; Department of Hematology, Ramos Mejía Hospital, Buenos Aires, Argentina., Montero VS; Department of Biochemistry, Center of Medical Education and Clinical Research 'Norberto Quirno' (CEMIC), Buenos Aires, Argentina., Rabinovich GA; Laboratory of Immunopathology, Institute of Biology and Experimental Medicine (IBYME), National Scientific Council of Scientific and Technical Research (CONICET), C1428, Buenos Aires, Argentina.; Department of Biological Chemistry, School of Exact and Natural Science, University of Buenos Aires, C1428, Buenos Aires, Argentina., Molinas FC; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina., Heller PG; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina., Lev PR; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina. paolal2002@gmail.com.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina. paolal2002@gmail.com., Marta RF; University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina. rfmarta2005@gmail.com.; Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina. rfmarta2005@gmail.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Feb 18; Vol. 9 (1), pp. 2208. Date of Electronic Publication: 2019 Feb 18.
DOI: 10.1038/s41598-018-38086-1
Abstrakt: Mechanisms leading to low platelet count in immune thrombocytopenia (ITP) involves both decreased production and increased destruction of platelet. However, the contribution of these pathologic mechanisms to clinical outcome of individual patients is uncertain. Here we evaluated different pathogenic mechanisms including in vitro megakaryopoiesis, platelet/megakaryocyte (MK) desialylation and MK apoptosis, and compared these effects with thrombopoyesis and platelet apoptosis in the same cohort of ITP patients. Normal umbilical cord blood-CD34+ cells, mature MK derived cells or platelets were incubated with plasma from ITP patients. Despite inhibition of thrombopoiesis previously observed, megakaryopoiesis was normal or even increased. Plasma from ITP patients affected the sialylation pattern of control platelets and this effect occurred concomitantly with apoptosis in 35% ITP samples. However, none of these abnormalities were observed in control MKs incubated with ITP plasma. Addition of mononuclear cells as immune effectors did not lead to phosphatidylserine exposure in MK, ruling out an antibody-mediated cytotoxic effect. These results suggest that both desialylation and apoptosis may be relevant mechanisms leading to platelet destruction although, they do not interfere with MK function. Analysis of these thrombocytopenic factors in individual patients showed no specific distribution pattern. However, the presence of circulating antiplatelet autoantibodies was associated with higher incidence of abnormalities. In conclusion, the causes of thrombocytopenia are multifactorial and may occur together, providing a rational basis for the use of combination therapies targeting concomitant ITP mechanisms in patients with refractory disease.
Databáze: MEDLINE
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