interleukin-8 and Venous-Thromboembolism

Background: Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTEs) after major trauma. Objectives : This study aimed to identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients. Methods: We performed a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios (PROPPR) study. Plasma levels of 27 cytokines/chemokines were measured by Bio-Plex at admission and 2, 4, 6, 12, 24, 48, and 72 h later. Patients who died from exsanguination or within 24 h were excluded. Mann-Whitney tests were performed to assess no-VTE and VTE groups at each time point. Multivariable logistic regression was used to determine the adjusted effects of inflammatory mediators on VTE risk. Results: Eighty-six of the 575 patients (15%) included developed VTE. Interleukin (IL)-1ra, IL-6, IL-8, IL-10, eotaxin, granulocyte colony-stimulating factor, interferon-γ-inducible protein, monocyte chemoattractant protein 1 (MCP-1), and chemokine ligand 5 (regulated on activation, normal T cell expressed and secreted) were all significantly increased among VTE patients. Multivariable analyses demonstrated that IL-6, IL-8, interferon-γ-inducible protein, and MCP-1 were independently associated with VTE. Cox proportional hazards modeling identified IL-6, IL-8, and MCP-1 as independent predictors of accelerated VTE development. We identified significant correlations between inflammation and markers of coagulation and endothelial activation. Conclusion: Sustained systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.

Topics: Chemokines; Humans; Inflammation; Inflammation Mediators; Interferon-gamma; Interleukin-6; Interleukin-8; Venous Thromboembolism

Patients with malignancy have higher risk of developing venous thromboembolism. The incidence among different groups of cancer patients varies considerably depending on clinical factors, the most important being tumor entity and stage. The study was approved by the local ethics committee on human research, and written informed consent was obtained from all the study participants. After written informed consent was obtained, a precise medical history was taken, with particular attention to questions about the presence of thrombotic risk factors at the onset of VTE. We retrospectively enrolled 50 patients with Venous Thromboembolism (DVT and PTE) having malignancy and 50 healthy controls from January 2020 to December 2020. DVT were diagnosed using peripheral vascular duplex ultrasonography while PTE was confirmed in all cases by computed tomography. Patients having treatment with anticoagulant therapy, recent surgery less than 8 days previously, refusal or inability to give informed consent, and inability for ascending contrast venography or inadequate results of the venographic examination were excluded from the study. Biomarkers have been specifically investigated for their capacity of predicting venous thromboembolism (VTE) during the course of disease. The relationships between inflammation markers e.g., IL-6, IL-8 and CRP as indicators of the inflammatory process and clinical venous thromboembolism need to be investigated. We investigated IL-6, IL-8 and CRP in 50 patients with venous thromboembolism having malignancy and reported that patients having venous thromboembolism have increased levels of IL-6, IL-8 and CRP (p value < 0.05). Our study concluded that in cancer patients, inflammatory biomarkers play significant role in developing venous thromboembolism. This supports the hypothesis that, markers of systemic inflammatory response are involved in development of thromboembolism in patients with malignancy.

Topics: Biomarkers; Humans; Incidence; Interleukin-6; Interleukin-8; Neoplasms; Pulmonary Embolism; Retrospective Studies; Risk Factors; Systemic Inflammatory Response Syndrome; Thrombosis; Venous Thromboembolism

Cancer immunotherapy is associated with several immune-related adverse events, but the relationship between immunotherapy and venous thromboembolism has not been thoroughly studied.. We conducted a retrospective cohort study of 1,686 patients who received immunotherapy for a variety of malignancies to determine the incidence of venous thromboembolism and the impact of venous thromboembolism on survival. To examine the potential role of inflammation in venous thromboembolism, we also profiled immune cells and plasma cytokines in blood samples obtained prior to initiation of immunotherapy in a sub-cohort of patients treated on clinical trials who subsequently did (N = 15), or did not (N = 10) develop venous thromboembolism.. Venous thromboembolism occurred while on immunotherapy in 404/1686 patients (24%) and was associated with decreased overall survival [HR=1.22 (95% CI 1.06-1.41), p<0.008]. Patients that developed venous thromboembolism had significantly higher pretreatment levels of myeloid-derived suppressor cells (5.382 ± 0.873 vs. 3.341 ± 0.3402, mean ± SEM; p=0.0045), interleukin 8 (221.2 ± 37.53 vs. 111.6 ± 25.36, mean ± SEM; p=0.016), and soluble vascular cell adhesion protein 1 (1210 ± 120.6 vs. 895.5 ± 53.34, mean ± SEM; p=0.0385).. These findings demonstrate that venous thromboembolism is an underappreciated and important immune-related adverse event associated with cancer immunotherapy, and may implicate an interleukin 8 and myeloid-derived suppressor cell-driven pathway in pathogenesis.

Topics: Humans; Immunotherapy; Incidence; Interleukin-8; Neoplasms; Retrospective Studies; Venous Thromboembolism

Venous thromboembolism (VTE) develops via a multicellular process on the endothelial surface. Although widely recognized, the relationship between inflammation and thrombosis, this relationship has been mostly explored in clinical studies by measuring circulating levels of inflammatory cytokines. However, the role of inflammatory cells, such as neutrophils, in the pathogenesis of VTE is not clear in humans.. To evaluate the adhesive properties of neutrophils, erythrocytes and platelets in VTE patients and to correlate findings with inflammatory and hypercoagulability marker levels.. Study group consisted of twenty-nine VTE patients and controls matched according to age, gender and ethnic background. Adhesive properties of neutrophils, erythrocytes and platelets were determined using a static adhesion assay. Neutrophil adhesion molecules expressions were evaluated by flow cytometry. Inflammatory and hypercoagulability marker levels were evaluated by standard methods. Residual vein occlusion (RVO) was evaluated by Doppler ultrasound.. No significant difference could be observed in platelet and erythrocyte adhesion between VTE patients and controls. Interestingly, VTE patients with high levels of D-dimer and RVO, demonstrated a significant increase in neutrophil adhesion, compared to controls and remaining patients. Inflammatory markers (IL-6, IL-8, TNF-α) were also significantly elevated in this subgroup, compared to other VTE patients. Adhesive properties of neutrophils correlated with IL-6 and D-dimer levels. Neutrophils adhesion molecules (CD11a, CD11b and CD18) were not altered in any of the groups.. These findings not only support the hypothesis of an association between inflammation and hypercoagulability, but more importantly, highlight the role of neutrophils in this process.

Topics: Adult; Aged; Biomarkers; Blood Platelets; Case-Control Studies; Cell Adhesion; Erythrocytes; Female; Fibrin Fibrinogen Degradation Products; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutrophils; Tumor Necrosis Factor-alpha; Venous Thromboembolism; Young Adult