Guidelines for Evaluation Hereditary Thrombophilia among Patients with Recurrent Pregnancy Loss and New Diagnostic Test

Recurrent pregnancy loss (RPL) affect up to 5% of women of reproductive age Thrombophilia is a condition associated with an increased tendency to venous thromboembolisim. In recent years, various studies have reported an association between thrombophilia and fetal loss, depending on the type of the thrombophilia (acquired versus hereditary), or the type of fetal loss (e.g. isolated, recurrent; early, late).

In the last two decades, numerous publications have appeared both in favor of and against prescribing anticoagulant drugs to improve the rate of live births and reduce the risk of placenta-mediated complications during pregnancy. While there is also still some controversy over which line to follow, anticoagulants are frequently used in clinical practice, as well as in assisted reproduction. Hereditary thrombophilia comprises both genetic deficit of physiological anticoagulant proteins (antithrombin, protein C and protein S), which decreases thrombin formation, as well as increased or decreased function of distinct coagulation factors due to mutations .In these patients, the genetic causes of underlying thrombotic risk typically include the Factor V Leiden (FVL) and PT G20210 mutations, which are widely known to have a marked functional effect .Furthermore, there is evidence to suggest that some genetic variants increase predisposition to thromboembolism by modifying components of the coagulation cascade. A systematic review confirmed that women with thrombophilia have higher risk of developing thromboembolism and complications during pregnancy.

New genetic markers associated with greater risk of venous thrombosis reported recently They include C46T Mutation in the FXII gene, ABO blood group haplotypes,Arg306Thr (F5 Cambridge) and Arg306Gly (F5 Hong Kong) mutations in the FV gene.R67X Mutation in the Serpin A10 gene, Ala384Ser mutation in the Serpin C1 gene andVal34leu Mutation in the FXIII gen.

Studies have been shown that using the new markers with genetic risk scores provide a better estimate of thromboembolic risk than a model based on FVL and prothrombine. New studies conducted in populations of women with gestational problems including RPL verify the greater clinical utility of this new test over FVL/PT.

In conclusion, now days hereditary thrombophilia evaluation among couples with RPL is not required by the guidelines. However, new tests including more genetic mutations of the coagulation factors along with clinical risk assessment should provide better clinical utility.