Altered fibrin clot properties in advanced lung cancer: strong impact of cigarette smoking

Med Oncol. 2019 Mar 19;36(4):37. doi: 10.1007/s12032-019-1262-4.

Abstract

Background: Dense 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.

Methods: We 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.

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, 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.

Conclusion: Advanced lung cancer is associated with the prothrombotic plasma clot phenotype largely driven by smoking.

Keywords: Clot lysis time; Fibrin clot; Lung cancer; Smoking; Thrombin generation.

MeSH terms

  • Aged
  • Case-Control Studies
  • Cigarette Smoking / blood*
  • Cotinine / blood
  • Female
  • Fibrin / metabolism*
  • Fibrin Clot Lysis Time
  • Humans
  • Lung Neoplasms / blood*
  • Male
  • Middle Aged
  • Phenotype
  • Thrombin / metabolism

Substances

  • Fibrin
  • Thrombin
  • Cotinine