Pathogenic Mechanisms Contributing to Thrombocytopenia in Patients with Systemic Lupus Erythematosus

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

Congreso; ISTH 2020 Virtual Congress; 2020

Background: Systemic lupus erythematosus (SLE) is an autoimmune condition developing thrombocytopenia in about 10-15% of cases.Aims: To investigate possible causes of low platelet count, including platelet apoptosis and desialylation as well as inhibition of platelet production.Methods: Twenty-five SLE patients with and without thrombocytopenia were included. Platelet apoptosis was studied by phosphatidylserine exposure, loss of mitochondrial membrane potential (ΔΨm), and active caspase 3 measurement; platelet activation by PAC-1 binding and P-selectin externalization;. plasma induction of normal platelet desialylation by Ricinus communis agglutinin I and peanut agglutinin binding; all by flow cytometry. Effect of SLE plasma on megakaryopoiesis and thrombopoiesis were evaluated using CD34+ hematopoietic progenitors isolated from normal blood cord.Results: Platelet apoptosis was found in platelets from 4 thrombocytopenic patients. Six patients had ex vivo platelet activation, three of them also displaying platelet apoptosis. Besides, plasma from SLE patients induced desialylation of normal platelets. While megakaryopoiesis was increased, thrombopoiesis (proplatelet count) was decreased in the presence of SLE plasma. Depletion of anti-platelet autoantibodies from SLE plasma reverted the inhibitory effect on thrombopoiesis. Overall, these abnormalities were more frequently observed in patients with active disease (SLEDAI>4) than in those patients with inactive disease (SLEDAI < or = 4).Conclusions: Platelet clearance due to apoptosis and desialylation, as well as inhibition of platelet production due to impaired thrombopoiesis, could be relevant mechanisms leading to thrombocytopenia in SLE. On the contrary, increased megakaryopoiesis, could help maintain normal platelet count in spite of the deteriorated thrombopoiesis in some SLE patients