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

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. © 2012 International Society on Thrombosis and Haemostasis.