PB0719 - Assessment of coagulation activation using thrombin generation assay in newly diagnosed acute myeloid leukemia

Background: Acute myeloid leukemia (AML) has increased the risk of bleeding and thromboembolism. Dysregulated coagulation activation may underlie mechanisms of bleeding and thromboembolism in AML.

Aims: We determined coagulation alteration using the thrombin generation assay to assess coagulation activation in AML.

Methods: Thrombin generation assay was performed in newly diagnosed AML patients at diagnosis and longitudinally monitored at different points during follow-up. Coagulation tests including fibrinogen, D-dimer and tissue factor antigen were also determined and compared to age-matched-healthy controls.

Results: Thirty-two AML patients were included. The mean age at diagnosis was 43 years. At diagnosis, peak thrombin generation and endogenous thrombin potential values of AML patients were not different from those of controls (193.8 nM vs 177.7 nM; p=0.43, 1,403.3 nM·min vs 1,524.7 nM·min; p=0.17). Fibrinogen levels were not different between both groups (316 g/dL vs 299 g/dL; p=0.3). D-dimer and TFAg levels were substantially increased in AML patients compared to controls (4,046.8 ng/mL vs 280.8 ng/mL; p< 0.001, 76.2 pg/ml vs 55.4 pg/ml; p=0.001). Nine (28%) patients had overt DIC. No differences in thrombin generation assay were detected after the initiation of chemotherapy on days 7, 30 and 180 during follow-up. D-dimer is greatly decreased during follow-up. Of 13 with bleeding at diagnosis, there were no differences in endogenous thrombin potential and peak thrombin generation values between bleeding and non-bleeding patients (1,434.9 nM·min vs 1,381.5 nM·min; p=0.69, 189.4 mM vs 197 nM; p=0.84). The platelet counts were lower (21,000/uL vs 75,000/uL; p=0.03), while D-dimer levels were higher in bleeding patients (5,865 ng/ml vs 2,492.1 ng/ml; p=0.01). No patients experienced thromboembolism throughout follow-up. There were no correlations between thrombin generation and coagulation activation and disease outcomes.

Conclusion(s): Thrombin generation assay failed to detect coagulation activation in newly diagnosed AML patients. D-dimer was significantly increased in AML patients and decreased after treatment, probably subsiding DIC.