PB2438 DEEP‐VEIN THROMBOSIS IN PATIENTS WITH FACTOR XI DEFICIENCY FROM THE SOUTH OF TUNISIA

Abstract

Background:Clotting factor XI (FXI) plays a separate role in hemostasis and in thrombosis. Recently, researches had shown that a FXI plasmatic activity (FXI: Act) greater than 95% could represent a thrombotic risk factor. FXI deficiency belongs to the rare bleeding disorders. However, in some reports, a reduced incidence of deep‐vein thrombosis (DVT) has been noticed in patients with a FXI defect.Aims:The aim of this study was to study the frequency of DVT and to evaluate the incidence of the most common prothrombotic molecular risk factors in FXI deficiency in the South of Tunisia.Methods:This study was carried out in 30 FXI deficient patients. The FXI: Act was performed by the coagulometric method. Genotyping for the G1691A Factor V Leiden (FVL) polymorphism was conducted using PCR‐AS (polymerase chain reaction‐specific allele) and the MTHFR C677T polymorphism was performed by PCR‐RFLP (polymerase chain reaction ‐ Restriction fragment length polymorphism). Our findings were compared to some prominent population‐based reports.Results:The mean age of our series was 36.7 years ± 18 and the sex ratio was about 0.43. 19 cases / 30 patients (63.3%) had a moderate FXI deficiency (FXI: Act between 20 and 59%) while 11 cases (36.6%) had a severe FXI defect (FXI: Act <20%). Our study revealed only two incident cases of DVT (6.6%) comparing to the meta‐analysis of Naess et al. which revealed a DVT's frequency over 10.9% (234 cases /2136 healthy controls). This result was actually lower than expected, leading to a lower risk of thrombosis in our patients. In regard to the prothrombotic molecular profile, the G1691A FVL polymorphism was noticed in four heterozygous patients (13.3%). Being similar to the expected incidence : 13.6% (34 cases /250 healthy blood donors from southern Tunisia (31 heterozygous variants and 3 homozygous variants), the FVL reduced incidence, couldn’t imply a lower risk of having a mutated FVL allele in our patients. Concerning the MTHFR C677T polymorphism, 11 patients had mutated alleles (nine heterozygous (34.6%) and two homozygous variants (7.7%)). The MTHFR C677T heterozygosity was slightly lower than in the controls’ incidence (51 heterozygous variants/ 100 healthy controls from northern Tunisia (51%)). However, two patients had presented the homozygous form of the MTHFR C677T polymorphism (7.7%) without any thrombosis symptom, whereas no homozygous variants were noticed in the controls’ group.Summary/Conclusion:Our study highlighted, as shown in the literature, that the FXI deficiency might protect against the DVT's occurrence. Indeed, the expected incidence of thrombotic events was higher than the results found in our series. Concerning the molecular exploration of the most common prothrombotic risk factors, our findings showed a lower incidence of the C677T MTHFR heterozygous form in FXI deficient patients comparing to the controls’ group, which leads to a lower predisposition to DVT, while the G1691A polymorphism of FVL's incidence was less conclusive. Added to that, the result of the two patients with a homozygous MTHFR genotype that had never presented any thrombotic or stroke accident, may confirm that the FXI deficiency provides a thrombotic protection to the patients. For this reason, the other prothrombotic markers such as the prothrombin G20210A mutation must be explored. Larger data and case‐control studies are mandatory to obtain better statistics especially that experimental studies are focusing on FXI as a new therapeutic target with anticoagulant properties in order to prevent postoperative thrombosis.