Extracellular vesicles exposing tissue factor for the prediction of venous thromboembolism in patients with cancer: A prospective cohort study

van Es, N., Hisada, Y., Di Nisio, M., Cesarman, G., Kleinjan, A., Mahe, I., Otten, H-M., Kamphuisen, P. W., Berckmans, R. J., Buller, H. R., Mackman, N. & Nieuwland, R., Jun-2018, In : Thrombosis Research. 166, p. 54-59 6 p.

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  • Extracellular vesicles exposing tissue factor for the prediction of venous thromboembolism in patients with cancer

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  • Nick van Es
  • Yohei Hisada
  • Marcello Di Nisio
  • Gabriela Cesarman
  • Ankie Kleinjan
  • Isabelle Mahe
  • Hans-Martin Otten
  • Pieter W. Kamphuisen
  • Rene J. Berckmans
  • Harry R. Buller
  • Nigel Mackman
  • Rienk Nieuwland

Introduction: The procoagulant activity of extracellular vesicles (EV) exposing tissue factor (TF) is a promising biomarker for venous thromboembolism (VTE) in cancer patients. We evaluated an in-house EV-TF activity assay (the fibrin generation test) for the prediction of cancer-associated VTE. We also compared the results with the fibrin generation tests to an EV-TF-dependent factor Xa generation assay in samples from pancreatic cancer patients.

Materials and methods: Data collected in a multinational, prospective cohort study were used. Patients with various types of advanced cancer were enrolled if chemotherapy was scheduled or started in the previous 3 months. Patients were followed for 6 months for the occurrence of VTE. The fibrin generation test was performed at baseline to measure EV-TF procoagulant activity.

Results: The fibrin generation test was performed in 648 patients with advanced cancer. The mean age was 62 years; 58% had distant metastasis. Forty patients (6.1%) developed VTE. Overall, a high fibrin generation test result was associated with a two-fold increased risk for VTE (HR 2.0; 95%-CI, 1.1-3.6). The association was stronger in patients with pancreatic cancer (HR 4.1; 95%-CI, 0.91-19) than in those with other tumor types (HR 1.5; 95%-CI, 0.72-3.1). Correlation between the FGT and the TF-dependent factor Xa generation assay in patients with pancreatic cancer was poor (Spearman's R = 0.35).

Conclusion: This study shows that a high EV-TF procoagulant activity as measured by the fibrin generation test is associated with an increased risk of VTE in cancer patients, in particular in those with pancreatic cancer. Future studies should aim to further improve the feasibility and accuracy of EV-TF activity assays.

Original languageEnglish
Pages (from-to)54-59
Number of pages6
JournalThrombosis Research
Publication statusPublished - Jun-2018


  • Biomarkers, Blood coagulation, Neoplasms, Predictive value of tests, Pulmonary embolism, Venous thrombosis, CLINICAL-PRACTICE GUIDELINES, PANCREATIC-CANCER, VIENNA CANCER, THROMBOSIS, MICROPARTICLES, ACTIVATION, BIOMARKERS

ID: 74729110