PB1832: Inflammation induced coagulation in acute myeloid leukemia

Abstract

Background: Patients with acute myeloid leukemia (AML) have an increased risk of thrombotic complications in the range of 4.2 - 5.2%. Aims: Our hypothesis is that inflammation is responsible for deterioration of coagulation in AML. Methods: Quantification of neutrophil extracellular traps (NETs) from peripheral blood of patients with AML by measurement of circulating cell-free DNA (cfDNA) and myeloperoxidase (MPO) activity. Inflammatory cytokines, coagulation factors and chemokines are measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry in peripheral blood, while fibrinolytic activity with fluorescent tissue-type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) assays. Results: The pro-inflammatory cytokines IL-1β and TNF-α were significantly increased in AML, but not the chemokines IL-8 and MCP-1. NETs were increased in the peripheral blood of patients with AML (p<0.05) as measured by cfDNA and MPO activity. Regarding coagulation, factor VIII (p<0.05) and adhesion molecule P-selectin (p<0.001) were increased in plasma. Fibrinolytic activity was 3-fold decreased in the plasma of patients with AML (p<0.01) as measured by tPA. In contrast, uPA levels were increased in patients with AML (p<0.05). Tissue factor (CD142+) inflammatory microparticles derived from monocytes (CD14+: 5.1±0.6, p<0.001), activated monocytes (CD14+/CD16+: 2.89±0.4%, p<0.05) and circulating endothelial cells (CD31+/CD144+: 4.08±0.5%, p<0.05) were increased in AML compared to healthy controls. Summary/Conclusion: Chronic inflammation is present in AML in parallel with reduced fibrinolysis and increased coagulation provoking the risk of thrombosis. A panel of the applied inflammatory/ procoagulant biomarkers can be used as a predictor of thrombosis in AML.