Nick van Es1, Yohei Hisada2, Marcello Di Nisio3, Gabriela Cesarman4, Ankie Kleinjan5, Isabelle Mahé6, Hans-Martin Otten7, Pieter W Kamphuisen8, René J Berckmans9, Harry R Büller5, Nigel Mackman2, Rienk Nieuwland9. 1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: n.vanes@amc.nl. 2. Department of Medicine, University of North Carolina at Chapel Hill, NC, USA. 3. Department of Medicine and Ageing Sciences, G. D'Annunzio University, Chieti, Italy. 4. Department of Hematology, National Cancer Institute Mexico, Mexico City, Mexico. 5. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. 6. Department of Internal Medicine, Hopital Louis Mourier, Paris, France. 7. Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands. 8. Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands; Department of Internal Medicine, Tergooi Hospital, Hilversum, The Netherlands. 9. Laboratory of Experimental Clinical Chemistry, Vesicle Observation Centre, Academic Medical Center, Amsterdam, The Netherlands.
Abstract
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.
INTRODUCTION: The procoagulant activity of extracellular vesicles (EV) exposing tissue factor (TF) is a promising biomarker for venous thromboembolism (VTE) in cancerpatients. 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 cancerpatients. 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 cancerpatients, in particular in those with pancreatic cancer. Future studies should aim to further improve the feasibility and accuracy of EV-TF activity assays.
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