Double inherited thrombophilias and adverse pregnancy outcomes: fashion or science?

To determine to what extent double inherited thrombophilias are associated with adverse obstetric complications correlated with fetoplacental insufficiency, such as preeclampsia, hemolytic anemia elevated liver enzymes and low platelet count (HELLP) syndrome, gestational hypertension, fetal growth restriction (FGR), intrauterine death (ID), abruptio placentae and disseminated intravascular coagulopathy.

Pregnant women coming to delivery were retrospectively divided into two groups: group A (controls) and group B (cases). Patients belonging to group B had one of the following: severe preeclampsia, HELLP syndrome, gestational hypertension, FGR, intrauterine death, abruptio placentae of disseminated intravascular coagulopathy. We detected methylenetetrahydrofolate reductase (MTHFR) A1298C, MTHFR C677T, factor V Leiden, PAI-1, mutant prothrombin G20210A, plasma homocysteine, antithrombin III, protein S and activated protein C resistance. Normal pregnant women or pregnant women with double defects were enrolled in this study.

The combination of MTHFR C677T mutation with PAI-1 (5G/5G) mutation was significantly linked with the occurrence of ID. HELLP syndrome was significantly related to the simultaneous presence of factor VIII and X mutations. The combination of MTHFR C677T with factor VIII mutation and the combination of factor II and V mutations were significantly related to the occurrence of abruptio placentae. We found an association between double isoforms MTHFR mutation and FGR.

It seems that some thrombophilias and a combination of thrombophilic factors carry a greater risk than others for a given adverse outcome. Further studies are needed to check the link between thrombophilic gene mutations and adverse pregnancy outcomes, such as recurrent miscarriages and deep venous thrombosis.