Prevalence of thrombophilia-associated mutations and their clinical significance in a large cohort of Lebanese patients

Abstract

Background: Mutations in the Factor V, Factor II and MTHFR genes are very high in the MENA region and have not been linked widely to specific entities in the hypercoagulation spectrum. In addition, the clinical effect of MTHFR alterations remains debatable. Aims: Determining the frequency of mutations in Lebanese patients referred for thrombophilia testing following a thrombotic event or for familial screening and investigating for the presence of a correlation with specific clinical events, location of thrombosis and recurrence rates. Methods: Laboratory results of Lebanese patients referred to the American University of Beirut Medical Center for thrombophilia testing from Jsanuary 2007 until December 2016 were reviewed. Molecular testing for Factor V (Factor V Leiden, G1691A), Factor II (G20210A) and MTHFR (C677T) in our CAP-accredited laboratory is based on the Vienna Lab (Viennalab diagnostics GmbH, Vienna, Austria) FV/PTH/MTHFR Strip Assay. Clinical information including age, gender, reason for testing, risk factors and history of recurrence were collected from the Electronic Health Records. Results: For the 2002 obtained cases, the male: female ratio was 1:2 (male = 32.7%, female = 67.3%). The age ranged from 4 days to 91 years with a median of 34 years. A G1691A mutation of Factor V was present in 36.5% of all patients (heterozygotes: 31.4%, homozygotes: 5.1%). Factor II (G20210A) was found in 11.8% (heterozygotes: 11.4%, homozygotes: 0.4%) and MTHFR (C677T) in 83.3% (heterozygotes: 62.4%, homozygotes: 20.9%). Double mutations were present in 674 cases (33.6%) and triple mutations in 41 cases (2%). Clinical data could be retrieved for 1000 patients, among which 353 (35.3%) presented for workup of infertility/recurrent pregnancy problems, 271 (27.1%) following a venous thromboembolism event (DVT and/or PE), 181 (18.1%) after an arterial stroke and 22.1% (n = 221) for familial screening. Statistically significant correlations were found between the presence of a Factor V or Factor II mutation and presentation for a venous thromboembolism (VTE) or recurrent pregnancy loss. No relation was found between the different types of prothrombotic mutations and VTE location or recurrence rates. Conclusion: This is the first study in the MENA region to evaluate the frequency of all gain of function thrombophilia genes in patients with a personal or familial history of thrombosis. The Lebanese population carries the highest rates of prothrombotic mutations worldwide. This has major implications on the application of proper screening and anticoagulation prophylaxis strategies in our region. © 2021 Elsevier B.V.