PB2434 GENETIC AND ACQUIRED THROMBOTIC RISK FACTORS IN CEREBRAL VENOUS THROMBOSIS: A STUDY FROM THE SOUTH OF TUNISIA.
Authors: B. Jardak, F. Megdiche, L. Mbarek, F. Kotti, H. Chaabane, H. Masmoudi, Z. Bahloul, C. Kallel
Journal: HemaSphere (2019)

Background: Cerebral Venous Thrombosis (CVT) affecting young adults is considered as an uncommon form of venous thrombosis with a prominent mortality rate (6%). The clinical phenotype may vary among patients as a result of many common prothrombotic risk factors. According to the literature, acquired and inherited thrombophilia should be explored in a constant manner following this thrombotic accident. Aims: Our objectives were to study the incidence of protein S (PS), protein C (PC), antithrombin (AT), factor V Leiden ( FVL ) G1691A polymorphism, prothrombin G20210A mutation, MTHFR C677T polymorphism and standardized antiphospholipid antibodies in 50 young Tunisian adults who suffered from CVT. Methods: 50 patients were carried out in this study and were referred to our laboratory from 2016 to 2018 following the occurrence of a cerebral venous thrombosis. Biological investigation included the PS and PC analysis by coagulometric methods (STACLOT® PROTEIN S ; STACLOT® PROTEIN C) and the AT analysis by a chromogenic method (STA‐CHROM‐AT diagnostica stago).Genotyping for factor V Leiden ( FVL ) G1691A polymorphism and the prothrombinG20210A mutation was detected by PCR‐AS (allele‐specific polymerase chain reaction) while the MTHFR C677T polymorphism was conducted using PCR‐RFLP (polymerase chain reaction ‐Restriction fragment length polymorphism). Lupus anticoagulant (LA) screening was performed by the STA‐R ® using, simultaneously, the PTT‐LA® and the dRVVT Screen®/ dRVVT Confirm® reagents. The anticardiolipin (aCL) and the anti ‐ beta 2 glycoprotein I (aβ2GPI) antibodies’ assays were performed by the immunological ELISA test. Results: The mean age of our patients was 30 ± 17 years old and the sex ratio was about 1.08. Among 50 patients, 11 cases (22 %) had presented thrombophilic abnormalities. Regarding the common congenital thrombophilia markers, our study revealed as follows: PS deficiency (4%), PC deficiency (4%) and none of the patients had an isolated inherited AT defect. Added to that, two patients had combined deficiencies in AT and PC. Molecular genotyping was explored in six patients, the frequencies of the molecular abnormalities were noticed in this manner: one case of ( FVL ) G1691A polymorphism (16.6%), two patients presented MTHFR C677T polymorphism (33.3%), all of them were in the heterozygous state, and a total absence of prothrombin G20210A mutation. Concerning the acquired thrombophilic factors, LA screening was positive in 6 cases /42 (14.3%), whereas, no significant levels of aCL and aβ2GPI antibodies were registered. Summary/Conclusion: According to recent Tunisian reports showing high frequencies of prothrombotic states that have reached 39% in CVT's patients, we consider that thrombophilia in our series is rather frequent in the South of Tunisia. The hereditary and acquired prothrombotic markers, have a presumably serious involvement in CVT's occurrence. The most prominent effect is that of MTHFR C677T and FVL polymorphisms, PS and PC deficiencies, while AT defect and prothrombin G20210A mutation remain to be elucidated. It is worth mentioning that combined defects do exist in our series. In regards to LA's positive results, it may necessitate a second positive confirmation after 12 weeks in order to exclude transient antibodies. It would be then interesting to attest the accountability of all these thrombotic risk factors as predisposing factors in CVT, through case‐control studies, in order to reach objective statistical findings.