Correlation between tumor necrosis factor-alpha and d-dimer levels in non-small cell lung cancer patients

Abstract

KEYWORDSNon-small-cell lung cancer; Fibrinolysis; Coagulation;Tumor necrosis factor-alpha; D-Dimer; Thrombin-antithrombin complexes Summary The present study was designed to investigate whether a correlation exists between IL-6, TNF-␣ and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n = 65, 53 males, mean age 65 ± 8, adenocarcinoma n = 32, squamous cancer n = 33) or chronic obstructive pulmonary disease (COPD) (n = 65, 51 males, mean age 67 ± 9) were studied. As control group 65 healthy donors (51 males, mean age 61 ± 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 g/ml) compared either to COPD patients (1.1 g/ml, P < 0.05) or controls (0.3 g/ml, P < 0.0001). Positive TNF-␣ levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P < 0.002) and 5% of controls (P < 0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P < 0.001). Median TATc levels were elevated in either NSCLC (6.9 g/l) or COPD (5.7 g/l) patients compared to controls (1.8 g/l, P < 0.0001). Elevated D-dimer levels were significantly associated to positive TNF-␣ levels in patients without distant metastasis (F = 4.3, P < 0.05). Moreover, TNF-␣ levels (P < 0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-␣ might be responsible for an activation of fibrinolysis in patients with NSCLC.

Association of ABO blood groups with von Willebrand factor, factor VIII and ADAMTS-13 in patients with lung cancer

“…Additionally, significant differences in the plasma levels of LDH, CEA, D-dimer, VWF and ADAMTS-13, and FVIII activity were observed between patients with and without distant metastasis. These results are in agreement with those of previous studies, which demonstrated an increased tendency for the development of coagulative and fibrinolytic disorders in patients with metastatic diseases (3,21). Furthermore, these results are similar to the observations of Oleksowicz et al (22), who identified increased VWF levels and ADAMTS-13 deficiencies in patients with metastatic tumors.…”

Predictive value of D-dimer plasma levels in response and progressive disease in patients with lung cancer

“…The process of fibrinolysis involves an enzymatic cascade which helps to break down cross-linked fibrin molecules [13]. The pathogenic mechanisms and the role of cytokines in coagulation regulation are complicated and are considered to be time-dependent and transient [19].…”

“…It has been reported that on a cellular level, tumor necrosis factor (TNF-␣) may directly activate the fibrinolytic system and the administration of TNF-␣ into healthy volunteers results in a transient activation of fibrinolysis [20,21]. It has been proposed that a similar mechanism may occur in the activation of fibrinolytic systems in NSCLC [13]. This is supported by the fact that the key intermediate cytokine, TNF-␣, has been correlated to the disease status of lung cancer patients [22][23][24].…”

“…It has been reported that haemostatic abnormalities contribute to solid tumor organisation, demarcation of the tumor from normal host tissues, the regulation of inflammatory cell accumulation, tumor angiogenesis and tumor stroma generation [12]; however the mechanism underlying these abnormalities is not completely understood. In practice, the elevation of the split products from crosslinked fibrin (D-dimers), was found in lung cancer patients, particularly those with extensive disease [13]. Sub-clinical activation of blood coagulation and fibrinolysis can occur in lung cancer [14,15].…”

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies

“…In fact, D-dimer can be elevated in up to 86% of patients with NSCLC [12]. A normal plasma value can thus exclude with very high probability the existence of venous thromboembolic disease, especially in patients with lung cancer [12,13].…”