Hypercoagulability Linked to Breast Cancer Depends On the Stage and the Duration of the Tumor Evolution
Authors: Chaari Mourad , Gerotziafas Grigoris T , Ghorbal Lilia , Galea Vassiliki , Ayadi Ines , Van Dreden Patrick , Adam Mariette , Bouzguenda Racem , Frikha Mounir , Daoud Jamel , Kallel Choumous , Woodhams Barry J , Elalamy Ismail 
Published: October 2019

Abstract
Abstract 3396

Introduction
The risk of venous thromboembolic event (VTE) in patients with cancer is particularly increased compared to normal population. It seems that this risk depends largely on the characteristics of the tumor, such as its site or its stage of evolution, and the anti-neoplasic treatment. The capacity of thrombin generation and D-dimers levels are two biological markers proposed for the stratification of the risk of VTE. We have analyzed thrombin generation and D-dimers levels in patients with breast cancer as markers of a hypercoagulable state, depending on the stage and the period of the tumor evolution.

Materials and methods
It is a prospective study carried out at the day hospital of the carcinology department of the University Hospital H. Bourguiba in Sfax-Tunisia, including patients with breast cancer at different stages of evolution and different period elapsed since cancer diagnosis. At the time of inclusion, a venous citrated blood sampling (3.2%) was made. The test of thrombin generation was carried out according to the technique of Calibrated Automated Thrombogram assay (CAT®, Diagnostica Stago, Asnières, France). The parameters of the thrombogram were analyzed: endogenous thrombin potential (ETP), peak of thrombin (peak) and mean rate index (MRI). D-dimers were measured using the STA®- Liatest® D-Di assay (Diagnostica-Stago).

Results
Sixty one patients were included. Their average age is 51.8 ± 10.9 years old. Depending on the stage of cancer disease, 3 sub-groups of patients were distinguished: early local stage (T1, n=16), advanced local stage (T2-T4; n=25) and metastatic stage (M; n=20). Considering the time passed since diagnosis, we have different periods : inferior to 6 months (n=26), 6 to 12 months (n=7), 12 to 36 months (n=15) and more than 36 months (n=13). The analysis of the different parameters of the thrombogram depending on the cancer stage revealed that patients with an advanced local stage and a period elapsed since cancer diagnosis inferior to 6 months had significantly higher values of ETP and thrombin peak (1708±247 nM.min and 379±80 nM) compared to those with an older cancer (1404±308 nM.min, p<0.05 and 321±52, p<0.05 respectively). The study of D-dimers levels depending on the stage of cancer revealed an increase of this marker according to the severity of the cancer. Patients with metastatic stages have the highest levels (1937 ± 2468 μg/l) compared to patients with an early local stage (615±456 μg/l, p<0.05 ). In addition, the period of time since cancer diagnosis does not have any influence on D-dimers levels.

Conclusion
The evaluation of the capacity of thrombin generation and D-dimers levels showed that these biological parameters are indeed linked to the stage of evolution and the severity of breast cancer. Therefore, these biological tests underlying an hypercoagulable state have a potential and complementary importance to stratify the risk of VTE in this context. This should be confirmed by the prospective follow-up of the thromboembolic risk existing in the patients with breast cancer.

Disclosures:
No relevant conflicts of interest to declare.