Biomarkers for the risk of thrombosis in pancreatic adenocarcinoma are related to cancer process

// Dorothee Faille 1, 2 , Marie-Charlotte Bourrienne 1, 2 , Emmanuelle de Raucourt 2, 3 , Luc de Chaisemartin 4, 5 , Vanessa Granger 4, 5 , Romaric Lacroix 6, 7 , Laurence Panicot-Dubois 6 , Pascal Hammel 8, 9 , Philippe Levy 10 , Philippe Ruszniewski 9, 10 , Nadine Ajzenberg 1, 2 and Vinciane Rebours 9, 10 1 Department of Hematology, Bichat Hospital, Assistance Publique-Hopitaux de Paris, Paris, France 2 Laboratory for Vascular Translational Science (LVTS), INSERM U1148, University of Paris Diderot, Sorbonne Paris Cite, Paris, France 3 Department of Hematology, Beaujon Hospital, Assistance Publique-Hopitaux de Paris, Clichy, France 4 Department of Immunology, Bichat Hospital, Assistance Publique-Hopitaux de Paris, Paris, France 5 Inflammation, Chemokines and Immunopathology, INSERM UMR 996, Paris-Sud University, Châtenay-Malabry, France 6 Vascular Research Centre of Marseille (VRCM), INSERM UMR 1076, Aix-Marseille University, Marseille, France 7 Haematology and Vascular Biology Laboratory, Conception Hospital, Assistance Publique-Hopitaux de Marseille, Marseille, France 8 Digestive Oncology Unit, Beaujon Hospital, Assistance Publique-Hopitaux de Paris, Clichy, France 9 Centre de Recherche sur l’Inflammation (CRI), INSERM UMR 1149, University of Paris Diderot, Sorbonne Paris Cite, Paris, France 10 Department of Pancreatology and Gastroenterology, Beaujon Hospital, Assistance Publique-Hopitaux de Paris, Clichy, France Correspondence to: Dorothee Faille, email: dorothee.faille@aphp.fr Keywords: D-dimers; microparticles; pancreatic cancer; thrombosis; tissue factor Received: April 07, 2018      Accepted: May 07, 2018      Published: May 29, 2018 ABSTRACT Background: Venous thrombo-embolic events (VTE) frequently occur in patients with pancreatic ductal adenocarcinoma (PDAC) and contribute to high morbidity and mortality. Objectives: To determine whether VTE biomarkers are related to cancer, inflammation or precancerous states and to assess their relevance to predict VTE in PDAC. Patients and Methods: We compared VTE biomarkers in patients with PDAC ( n = 42), intraductal papillary mucinous neoplasm of the pancreas (IPMN, n = 48) or chronic pancreatitis ( n = 50). PDAC patients were followed-up for 6 months. Results: Factor VIII, D-dimers, von Willebrand factor, free tissue factor pathway inhibitor and microvesicle-tissue factor (MV-TF) activity were higher in PDAC patients compared to patients with IPMN or chronic pancreatitis. PDAC patients with metastasis presented higher D-dimers and MV-TF activity compared to patients with localized lesions, but elevation of D-dimers was dependent on tumor size. In multivariate analysis, elevated D-dimers (≥2.16 μg/mL) or MV-TF activity (≥2.37 pg/mL) were significant risk factors for VTE in PDAC patients, after adjustment for age and sex (HR 4.9 [1.0–23.1] or HR 10.5 [1.5–72.4], mean [interquartile range], respectively). Cumulative probability of VTE at 6 months was higher in patients with elevated D-dimers (56.3% vs 15.6%, p = 0.009) and in patients with high MV-TF activity (74.3% vs 21.7%, p = 0.01). Conclusions: VTE biomarkers including D-dimers and MV-TF activity are not related to inflammation but rather to cancer process and dissemination. D-dimers and MV-TF activity are associated to future VTE in PDAC patients and could help identify patients who could benefit from thromboprophylaxis.