Tissue Factor As a Predictor of Recurrent Venous Thromboembolism in Malignancy: Biomarker Analyses of the CATCH Trial

J Clin Oncol. 2017 Apr 1;35(10):1078-1085. doi: 10.1200/JCO.2016.67.4564. Epub 2016 Dec 28.


Purpose Circulating tissue factor (TF) has been studied as a biomarker for predicting initial, but not recurrent, venous thromboembolism (VTE) in cancer, a setting in which predictors are incompletely understood. We evaluated the association of TF, clinical risk factors, and other biomarkers measured at the time of initial VTE with recurrent VTE in a prespecified analysis of the CATCH (Comparison of Acute Treatments in Cancer Hemostasis) trial. Methods CATCH was a randomized, multicenter trial that investigated tinzaparin 175 IU/kg once daily or dose-adjusted warfarin for 6 months in patients with cancer and acute, symptomatic VTE. TF ELISA, soluble P-selectin, d-dimer, FVIII, and C-reactive protein were assayed. Fisher's exact test was used to screen for association with VTE; competing risk regression analysis of time to recurrent VTE was conducted, accounting for multiple variables. Results The study population comprised 900 patients (recurrent VTE, n = 76; 8.4%). Of these patients, 805 had samples available for TF assay. Mean and median TF levels were 72.5 pg/mL and 50.3 pg/mL, respectively (range, 15.6 pg/mL to 4,798 pg/mL). Patients in the highest quartile of TF experienced the greatest VTE recurrence (> 64.6 pg/mL; 38 [19%] of 203 patients v 34 [6%] of 602 patients; relative risk, 3.3; 95% CI, 2.1 to 5.1; P < .001). In competing risk regression analysis of time to recurrent VTE, TF remained strongly associated with recurrent VTE (subdistribution hazard ratio [SHR], 3.3; 95% CI, 1.7 to 6.4). Other significant variables included venous compression from mass (SHR, 3.1; 95% CI, 1.4 to 6.5) and hepatobiliary cancer (SHR, 5.5; 95% CI, 2.3 to 13.6). Conclusion This is the first report, to our knowledge, to describe TF as a potential biomarker of recurrent VTE in patients with cancer who are on anticoagulation treatment. A risk-adapted strategy could help identify high-risk patients who may benefit from more intensive anticoagulation approaches.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Factor VIII / metabolism
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinolytic Agents / therapeutic use
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Neoplasms / complications*
  • Neoplasms / therapy
  • P-Selectin / blood
  • Predictive Value of Tests
  • Prospective Studies
  • Recurrence
  • Risk Factors
  • Thromboplastin / metabolism*
  • Time Factors
  • Tinzaparin
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / etiology


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • P-Selectin
  • fibrin fragment D
  • Tinzaparin
  • Factor VIII
  • C-Reactive Protein
  • Thromboplastin