Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients

J Thromb Haemost. 2012 Jul;10(7):1363-70. doi: 10.1111/j.1538-7836.2012.04754.x.

Abstract

Background: Tissue factor (TF) expression by tumors contributes to tumor growth. Release of TF-positive microparticles (MPs) may contribute to venous thromboembolism (VTE).

Objectives: To conduct a prospective cohort study to determine whether elevated MP-associated TF (MP-TF) activity is predictive of VTE and mortality in four cancer types.

Patients/methods: We determined MP-TF activity in pancreatic, gastric, colorectal and brain cancer patients. We used a chromogenic endpoint assay for all patients and also a chromogenic kinetic assay for patients with pancreatic and brain cancer.

Results: During follow-up, 12/60 (20%) pancreatic, 6/43 (14%) gastric, 12/126 (10%) colorectal and 19/119 (16%) brain cancer patients developed VTE; 46/60 (77%), 30/43 (70%), 47/126 (37%) and 67/119 (56%), respectively, died. MP-TF activity levels were highest in pancreatic cancer. We did not find a statistically significant association of MP-TF activity with the risk of VTE in any of the four cancer types by using two statistical methods. An association of MP-TF activity with the risk of mortality was detected in pancreatic cancer with the endpoint assay (hazard ratio [HR] 1.8 and 95% confidence interval [CI] 1.4-2.3 per doubling of activity, P < 0.001) and the kinetic assay (HR 1.2, 95% CI 1.1-1.4, P < 0.001); adjustment for type of treatment was not performed. In pancreatic cancer, MP-TF activity correlated with D-dimer level (endpoint assay, r = 0.51; chromogenic assay, r = 0.48), and a correlation between assays (r = 0.61) was found.

Conclusion: MP-TF activity was not associated with future VTE in pancreatic, gastric, colorectal and brain cancer. However, we found a strong association of MP-TF activity with mortality in pancreatic cancer. MP-TF activity might be reflective of an aggressive pancreatic cancer phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Neoplasms / blood*
  • Brain Neoplasms / complications
  • Brain Neoplasms / mortality
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Gastrointestinal Neoplasms / blood*
  • Gastrointestinal Neoplasms / complications
  • Gastrointestinal Neoplasms / mortality
  • Humans
  • Male
  • Middle Aged
  • Probability
  • Prospective Studies
  • Survival Rate
  • Thromboplastin / metabolism*
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / complications
  • Venous Thromboembolism / mortality

Substances

  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Thromboplastin