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. 2018 May 29;9(41):26453-26465.
doi: 10.18632/oncotarget.25458.

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

Dorothée 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 Lévy  10 , Philippe Ruszniewski  9   10 , Nadine Ajzenberg  1   2 , Vinciane Rebours  9   10
Affiliations

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

Dorothée Faille et al. Oncotarget. .

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.

Keywords: D-dimers; microparticles; pancreatic cancer; thrombosis; tissue factor.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1. Pairwise comparison of baseline biomarker levels according to pancreatic disease subgroup: chronic pancreatitis (CP), intraductal papillary mucinous neoplasm (IPMN), pancreatic ductal adenocarcinoma (PDAC)
P-values for *Mann-Whitney test or Ψlogistic regression analysis adjusted on age, sex, fibrinogen and interleukin-6 levels.
Figure 2
Figure 2. Cumulative incidence of VTE among cancer patients according to levels of D-dimers, MV-TF activity, TAT or CA-19-9 (<75th percentile or ≥75th percentile)
P-values for log-rank test.
See this image and copyright information in PMC

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