Changes in plasma levels of IL-6 and D-dimer in high-risk thrombosis cancer patients undergoing chemotherapy

Abstract

Background: Cancer and chemotherapy are venous thromboembolism (VTE) risk factors. The immune system and inflammation are essential in cancer-associated thrombosis's pathogenesis. Chemotherapy can induce inflammatory conditions that trigger the nuclear factor kappa B (NF-κB) signaling pathway to produce proinflammatory cytokines. Interleukin 6 (IL-6) improves procoagulant status primarily by inducing tissue factor (TF) expression. Tissue factor expression triggers the coagulation system, characterized by increased levels of D-dimer. This study assessed the change in plasma levels of IL-6 and D-dimer changed in high-risk thrombosis cancer patients undergoing chemotherapy. Methods:  This study was a prospective cohort study of 54 newly diagnosed high-risk thrombosis cancer patients undergoing chemotherapy in Dr. Kariadi General Hospital from January 2021 to September 2021 based on inclusion and exclusion criteria. IL-6 and D-dimer concentrations were collected a day before and after chemotherapy. IL-6 measured by ELISA method and D-dimer measured by the turbidimetry chromogenic immunoassay method. We did correlation test, compared mean, and subgroup analysis. The p-value<0.05 was significant.   Results: There was a positive correlation between plasma levels of IL-6 and D-dimer both pre- and post-chemotherapy (r=0.36; 95% CI (0.1-0.6); p=0.006 and r=0.45; 95% CI (0.2-0.6); p=<0.001, respectively). Post-chemotherapy plasma IL-6 (61.0±84.9 pg/mL) was significantly lower (p=0.022) than pre-chemotherapy (102.4±141.6 pg/mL). Subgroup analysis based on risks of thrombosis showed a significant decrease in plasma levels of IL-6 in the higher risk cancer group of thrombosis post-chemotherapy compared with the low risk cancer group (77.7±144.1 pg/mL vs -0.9±127.8 pg/mL; p=0.037). There was an increase in D-dimer plasma levels post-chemotherapy, but it was not statistically significant (2598.1±2487.8 µg/ml vs 3098.6±3547.4 µg/ml; p=0.512). The subgroup analysis based on blood type, tumor stage, chemotherapy regimen, and risk of thrombosis showed no significant differences in delta plasma IL-6 and D-Dimer levels pre- and post-chemotherapy. Conclusion: In high-risk thrombosis cancer patients who underwent chemotherapy, there was a statistically significant decrease in plasma levels of IL-6 post-chemotherapy. There was an increase in D-dimer plasma levels post-chemotherapy, but it was not statistically significant.