H. Baccouche

Tissue factor over-expression by human pancreatic cancer cells BXPC3 is related to higher prothrombotic potential as compared to breast cancer cells MCF7

Cancer histology influences the risk of venous thromboembolism and tissue factor (TF) is the key molecule in cancer-induced hypercoagulability. We investigated the relation between TF expression by pancreatic and breast cancer cells (BXPC3 and MCF7 respectively) and their capacity to trigger in vitro thrombin generation in normal human plasma. Flow cytometry and Western blot analysis for TF expression were performed using murine IgG1 monoclonal antibody against human TF. Real-time PCR for TFmRNA was also performed. Activity of TF expressed by cancer cells was measured with a specific chromogenic assay. Thrombin generation in PPP was assessed using calibrated automated thrombogram. Cancer cells were added to platelet poor plasma from healthy volunteers. In separate experiments cells were incubated with the anti-TF antibody at concentration that completely neutralized the activity of recombinant human TF on thrombin generation. BXPC3 cells expressed significantly higher amounts of functional TF as compared to MCF7 cells. Incubation of BXPC3 and MCF7 cells with PPP resulted in acceleration of the initiation phase of thrombin generation. BXPC3 cells manifested higher procoagulant potential than MCF7 cells. The incubation of BXPC3 or MCF7 cells with the anti-TF monoclonal antibody which resulted in reversal of their effect on thrombin generation. The present study establishes a link between the amount of TF expressed by cancer cells with their procoagulant activity. Both studied types of cancer cells trigger thrombin generation but they have different procoagulant potential. The procoagulant activity of BXPC3 and MCF7 cells is related to the amount of TF expressed. Kinetic parameters of thrombogram are the most relevant for the detection of the TF-dependent procoagulant activity of cancer cells. TF expression is one of the mechanisms by which cancer cells manifest their procoagulant potential but it is not the unique one. The present experimental model will allow the characterization the procoagulant fingerprint of cell lines from the same or different histological types of cancer.

Cerebral Venous Thrombosis: A Tunisian Monocenter Study on 160 Patients

Objective: Data regarding cerebral venous thrombosis in North Africa are scarce. This study aims to identify the clinical features, risk factors, outcome, and prognosis of cerebral venous thrombosis in Tunisia. Methods: Data of 160 patients with radiologically confirmed cerebral venous thrombosis, hospitalized in Mongi Ben Hmida National Institute of Neurology (Tunis, Tunisia), were retrospectively collected and analyzed. Results: The mean age was 37.3 years with a female predominance (83.1%). The mode of onset was subacute in most cases (56.2%). Headache was the most common symptom (71.3%), and focal neurologic symptoms were the main clinical presentation (41.8%). The most common sites of thrombosis were the superior sagittal sinus (65%) and the lateral sinus (60.6%). More than 1 sinus was involved in 114 (71.2%) patients. Parenchymal lesions observed in 85 (53.1%) patients did not correlate with cerebral venous thrombosis extent. Major risk factors were obstetric causes (pregnancy and puerperium) found in 46 (38.6% of women aged <50 years) patients, followed by anemia (28.1%) and congenital or acquired thrombophilia (16.2%). Mortality rate was of 6.6%. Good outcome at 6 months (modified Rankin Scale ≤2) was observed in 105 (87.5%)of 120 patients available for follow-up. Predictors of poor outcome were altered consciousness and elevated plasma C-reactive protein levels. Conclusion: Clinical and radiologic presentation of cerebral venous thrombosis in Tunisia was quite similar to other parts of the world with, however, a particularly high frequency of obstetric causes. Plasma C-reactive protein level should be considered as a prognostic factor in CVT.

AB0469 Fibrinolytic parameters abnormalities in tunisian patients with behçet’s disease. correlations with clinical presentation, activity, and severity of the disease.

Background The pathogenesis of Behçet’s disease (BD) remains unsolved. Endothelial damage and/or defects in coagulation or fibrinolysis are thought to take a part. Objectives Our aim was to determine d-dimers levels, tissue type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) in Tunisian patients with BD and to compare them with matched healthy controls. We also investigated the relation of these findings to patients’ clinical features, activity and severity. Methods The patient group included 57 BD (International Study Group criteria). According to the Yosipovitch severity scale, patients were divided into three subgroups: mild, moderate and severe disease. The activity index has been elaborated according to the Yazici scale. We excluded all patients with other physiological and pathological situations that may increase d-dimer. The control group consisted of Tunisian healthy individuals matched for age and sex. Levels of d-dimers were determined by a quantitative assay test and Plasma concentrations of t-PA and PAI-1 were determined by enzyme linked immunoabsorbent assay (ELISA). Results We included 57 BD patients (sex ratio M/F: 42/15, mean age: 40 years). One patient was excluded from statistical analysis due to a high rate of d-dimers (10µg/ml). The frequency of positive d-dimer was significantly higher in BD ptients than in healthy controls (17 (30%) vs 8 (13.8%) p=0.03). Table 1 summarizes the variation of d-dimer’s positivity according to demographic characteristics, clinical features, activity scale, and severity in BD patients. Financial limitations allowed us to realize t-Pa determination only in 42 patients and 44 healthy controls. The average rate of t-PA patients (4.85 ± 7.36 ng / ml) was lower than that of controls (5.62 ± 8.49 ng/ml). No significant correlation was found between the average t-PA, clinical manifestations and disease activity. The comparison of the frequencies of the different clinical manifestations depending on the average of PAI-1 showed a significantly lower level during ocular involvement (p=0.03). Average rates of PAI-1 were elevated in active forms of the disease. Conclusions The scarcity of publications on fibrinolytic abnormalities in BD does not help us to an easy interpretation of these results and their implication in the pathogenesis of the disease as a causative agent or a consequence, even if this seems to be most likely. Disclosure of Interest None Declared