Abstract
BackgroundDense fibrin networks resistant to lysis have been reported in patients at high risk of thromboembolism. Little is known about fibrin clot properties in cancer. We investigated fibrin clot properties and their determinants in patients with inoperable lung cancer.MethodsWe enrolled 150 patients with advanced lung cancer prior to therapy and 90 control subjects matched by age, sex, cardiovascular disease, and diabetes. Plasma clot permeability (Ks), turbidimetric analysis of clot formation, clot lysis time (CLT), microparticle-associated tissue factor (MP-TF) activity, thrombin generation, and serum cotinine levels were determined.ResultsLung cancer patients, compared with controls, formed at a faster rate (− 8.1% lag phase) denser plasma fibrin networks (− 27.2% Ks) that displayed impaired lysis (+ 26.5% CLT), along with 19.5% higher MP-TF activity and 100% higher peak thrombin generated, also after adjustment for potential confounders. Cotinine levels were associated with fibrin maximum absorbance (r = 0.20, p = 0.016) and Ks (r = − 0.50, p < 0.0001) in cancer patients. On multivariate regression analysis, an increase in cotinine levels was a predictor of low Ks (the lower quartile, < 5.8 × 10−9 cm2; odds ratio = 1.21 per 10 ng/ml, 95% confidence interval 1.02–1.46), but not CLT.ConclusionAdvanced lung cancer is associated with the prothrombotic plasma clot phenotype largely driven by smoking.
Highlights
Lung cancer is the leading cause of cancer death worldwide [1]
We demonstrated that the prothrombotic plasma clot phenotype, including faster formation of fibrin clots, reduced fibrin network porosity, and impaired clot lysability, characterizes patients with advanced lung cancer
These prothrombotic alterations showed no relationship with increased plasma D-dimer or thrombin generation, except the weak association between clot lysis time (CLT) and endogenous thrombin potential (ETP), suggesting the impact of other factors on fibrin clot structure and function in cancer
Summary
Lung cancer is the leading cause of cancer death worldwide [1]. The 5-year survival rate for stage IIIA, IIIB, and IV nonsmall-cell lung cancer (NSCLC) is about 14%, 5%, and 1%, respectively [2], while 5-year survival rates for stage II, III, and IV small-cell lung cancer (SCLC) are 19%, 8%, and 2%, respectively [3]. Venous thromboembolism (VTE) associated with a 50% higher risk of death occurs in approximately 3% of lung cancer patients [5, 6]. Chemotherapy is associated with threefold higher risk for VTE in lung cancer patients [9]. We investigated fibrin clot properties and their determinants in patients with inoperable lung cancer. Results Lung cancer patients, compared with controls, formed at a faster rate (− 8.1% lag phase) denser plasma fibrin networks (− 27.2% Ks) that displayed impaired lysis (+ 26.5% CLT), along with 19.5% higher MP-TF activity and 100% higher peak thrombin generated, after adjustment for potential confounders. Cotinine levels were associated with fibrin maximum absorbance (r = 0.20, p = 0.016) and Ks (r = − 0.50, p < 0.0001) in cancer patients. Conclusion Advanced lung cancer is associated with the prothrombotic plasma clot phenotype largely driven by smoking
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