Biomarkers for the risk of thrombosis in pancreatic adenocarcinoma are related to cancer process
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Dorothée Faille1,2, Marie-Charlotte Bourrienne1,2, Emmanuelle de Raucourt2,3, Luc de Chaisemartin4,5, Vanessa Granger4,5, Romaric Lacroix6,7, Laurence Panicot-Dubois6, Pascal Hammel8,9, Philippe Lévy10, Philippe Ruszniewski9,10, Nadine Ajzenberg1,2 and Vinciane Rebours9,10
1Department of Hematology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
2Laboratory for Vascular Translational Science (LVTS), INSERM U1148, University of Paris Diderot, Sorbonne Paris Cité, Paris, France
3Department of Hematology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
4Department of Immunology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
5Inflammation, Chemokines and Immunopathology, INSERM UMR 996, Paris-Sud University, Châtenay-Malabry, France
6Vascular Research Centre of Marseille (VRCM), INSERM UMR 1076, Aix-Marseille University, Marseille, France
7Haematology and Vascular Biology Laboratory, Conception Hospital, Assistance Publique-Hôpitaux de Marseille, Marseille, France
8Digestive Oncology Unit, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
9Centre de Recherche sur l’Inflammation (CRI), INSERM UMR 1149, University of Paris Diderot, Sorbonne Paris Cité, Paris, France
10Department of Pancreatology and Gastroenterology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, France
Dorothée Faille, email: [email protected]
Keywords: D-dimers; microparticles; pancreatic cancer; thrombosis; tissue factor
Received: April 07, 2018 Accepted: May 07, 2018 Published: May 29, 2018
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.
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