Pathogenic mechanisms contributing to thrombocytopenia in patients with Systemic Lupus Erythematosus.

GLEMBOTSKY AC; COLLADO V; GRODZIELSKI M; GOETTE NP; BARONI PIETO MC; MARIN OYARZÚN CP; PISONI C; GONZALEZ J; MARTA RF; LEV PR; GOMEZ G; GOMEZ R; HELLER PG

Congreso; International Society of Thrombosis and Haemostasis ISTH 2020 virtual congress; 2020

International Society of Thrombosis and Haemostasis ISTH

Pathogenic mechanisms contributing to thrombocytopenia in patients with Systemic Lupus Erythematosus M. Constanza Baroni Pietto1,2, Paola R Lev1,2, Ana C Glembotsky1,2, Cecilia P. Marín Oyarzún1,2, Graciela Gomez3, Victoria Collado3, Cecilia Pisoni4, Ramiro Gomez5, Matías Grodzielski1,2, Jacqueline Gonzalez6, Paula G Heller1,2, Nora P Goette1 and Rosana F Marta1,2*. 1University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina; 2Department of Experimental Hematology, Institute of Medical Research (IDIM), National Scientific and Technical Research Council (CONICET), University of Buenos Aires, Buenos Aires, Argentina; 3Department of Reumatology, University of Buenos Aires, Institute of Medical Research A Lanari, Buenos Aires, Argentina; 4Department of Reumatology, Center of Medical Education and Clinical Research ?Norberto Quirno? (CEMIC), Buenos Aires, Argentina; 5Department of Reumatology, University of Buenos Aires, Clinical Hospital ?José de San Martín?, Buenos Aires, Argentina; 6Department of Hematology, Durand Hospital, Buenos Aires, Argentina.Systemic lupus erythematosus (SLE) is characterized by production of myriad of autoantibodies. Patients develop thrombocytopenia in 10-15% of cases. Here, we investigated possible causes of thrombocytopenia, including platelet apoptosis, desialylation and inhibition of platelet production in SLE. Twenty-five patients with and without thrombocytopenia were studied. Apoptosis assessed by phosphatidylserine exposure, loss of mitochondrial membrane potential, and active caspase 3 measurement, was found in platelets from 4 thrombocytopenic patients. Desialylation of normal platelet glycoproteins was induced by 67% SLE plasma samples (Ricinus communis agglutinin I and peanut agglutinin binding). Concerning desialylation, thrombocytopenic SLE plasma tended to be more harmful than non-thrombocytopenic samples.To evaluate the effect of SLE plasma on platelet production, megakaryopoiesis was studied in normal CD34+ hematopoietic progenitors incubated with 10% SLE plasma for 12 days. Additionally, normal mature megakaryocytes obtained after 12-days plasma-free culture of CD34+ cells were supplemented with 10% SLE or control plasma to evaluate proplatelet formation (PPF) at day 15. While megakaryopoiesis was increased, PPF was decreased in the presence of SLE plasma (both, Mann-Whitney test p