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

Abstract

Budi Setiawan,1 Widi Budianto,1 Tri Wahyu Sukarnowati,1 Daniel Rizky,1 Eko Adhi Pangarsa,1 Damai Santosa,1 Rahajuningsih Dharma Setiabudy,2 Catharina Suharti1 1Hematology-Medical Oncology Division, Internal Medicine Department, Faculty of Medicine, Diponegoro University/Dr. Kariadi Hospital, Semarang, Indonesia; 2Clinical Pathology Department, Faculty of Medicine, University of Indonesia, Jakarta, IndonesiaCorrespondence: Budi Setiawan, Hematology-Medical Oncology Division, Internal Medicine Department, Faculty of Medicine, Diponegoro University/Dr. Kariadi Hospital, Jl. Dr. Soetomo No. 16, Semarang, Indonesia, Email [email protected]: 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.Keywords: inflammation, activation of coagulation, DVT, high-risk thrombosis, cancer patients

Keywords

• inflammation
• activation of coagulation
• dvt
• high risk thrombosis
• cancer patients