Correlation of Inflammation and Coagulation Markers with the Incidence of Deep Vein Thrombosis in Cancer Patients with High Risk of Thrombosis

Abstract

Background Deep vein thrombosis (DVT) is a common complication and the second leading cause of death in cancer patients. Pro-inflammatory stimuli in the cancer microenvironment induce nuclear factor kappa B (NF-κB) signaling pathway that plays an integral role in immunothrombosis mechanism. Objective To investigate the role of inflammatory and coagulation biomarkers in the development of DVT in cancer patients with high risk of thrombosis (Khorana score ≥2). Subjects and methods This study was a cross-sectional study at Dr. Kariadi General Hospital. The serum levels of proinflammatory cytokines, ie, NF-κB, interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and coagulation biomarkers, ie, tissue factor (TF), prothrombin fragment F1+2 (F1+2), fibrinogen and D-dimer were measured in newlydiagnosed cancer patients with a highrisk of thrombosis. Color duplex sonography was used for DVT screening. Results From January to November 2021, there were 83 eligible patients. DVT was confirmed in 8 subjects (9.63%). Univariate analysis revealed a significant difference between the median age of patients with DVT compared to non-DVT patients, 49.5 years (range: 23–60 years) and 42 years (range: 19–60 years), with p=0.046. D-dimer level was higher in DVT patients [(6.020 µg/L, range 2.090–20.000) vs (1.940 µg/L, range 270–20.000), p=0.005]. Multivariate analysis revealed age and D-dimer were significantly correlated with DVT incidence. In all patients, there were significant positive correlations between several inflammatory and coagulation activation parameters, which were IL-6 with D-dimer and F1+2, CRP with F1+2 and D-dimer as well as TNF-α with F1+2. However, these findings were not shown in DVT patients. Conclusion In cancer patients with a high risk of thrombosis, age and D-dimer level are the significant variables towards the incidence of DVT. In patients with DVT, there was no significant correlation between inflammatory and coagulation activation parameters.

Development of an algorithm for identifying paraneoplastic ischemic stroke in association with lung, pancreatic, and colorectal cancer

“…Our more detailed analysis revealed that for strokes associated with LPC cancers, but neither breast and prostate cancers nor bacterial endocarditis, steep increases in the average number of ischemic territories depending on both higher CRP and LDH levels were characteristic. Our finding corresponds quite well to observations that CRP positively correlates with D-dimers in paraneoplastic coagulopathy associated with venous thrombosis 43 and higher D-dimer levels in turn with a higher number of ischemic territories in cancer-associated stroke. 19 , 47 In summary, our findings reported here as well as previous reports are compatible with the hypothesis that the extent to which certain tumors, especially LPC cancer, induce inflammation dictates the activation of coagulation and thereby multiple ischemic events typical for paraneoplastic ischemic stroke.…”

“… 28 , 41 In addition, in paraneoplastic venous thrombosis, D-dimers strongly correlate with inflammatory blood markers. 43 Interestingly, high blood levels of some epithelial glycoproteins commonly used as tumor markers for carcinomas, that is, CA-125 aka Mucin-16, are associated with paraneoplastic ischemic stroke. 44 Experimentally, injecting these proteins into the circulation directly activates coagulation through adhesion-dependent, reciprocal activation of neutrophils and platelets.…”

Relationship between systemic inflammatory response and hypercoagulation in patients with immuno-inflammatory rheumatic diseases

“…Thus, there is formed a self-sustaining vicious pathogenetic circle of pathological process, which becomes independent of the damage factors at a certain stage of development. This process, called "thromboinflammation" or "immunothrombosis" is considered today as a universal pathogenetic mechanism of many acute and chronic diseases [1,5,8,10,11]. The results of the present study showed that the risk of hypercoagulation increases with increasing severity of SIR.…”

Deciphering the triad of endothelial glycocalyx, von Willebrand Factor, and P-selectin in inflammation-induced coagulation

“…Cancer patients also experience an increased affinity for thrombosis and concurrent venous inflammation ( Setiawan et al, 2022 ). As an acquired thrombophilia, cancer inflammation in the microenvironment induces a pro-inflammatory response including the release of Tumor Necrosis Factor Alpha (TNF-alpha) and cytokines including interleukins 1a, 6, 17, and 18 ( Setiawan et al, 2022 ). This inflammation is responsible for widespread endothelial cell damage and concurrent risk of thrombotic episodes.…”