Combined Thrombophilia and Obstetric Complications

Gestational vascular complications are a major cause of maternal and fetal morbidity. A growing body of evi- dence suggests significant correlation of inherited and acquired thrombophilia with pregnancy loss, pre-eclampsia, ec- lampsia, placental abruption, intrauterine growth restriction (IUGR), and intra uterine fetal death (IUFD). Placental patho- logical findings in women with thrombophilia are characterized by thrombosis and fibrin deposition to a greater degree than in normal pregnancy (1). The term Combined Thrombophilia is used when more than one prothrombotic conditions exist at the same time. As per definition any added prothrombotic diathesis promotes pregnancy to a combined thrombo- philic state (1, 2). Thrombophilic risk factors are common and can be found in 15% to 25% of Caucasian population. The combination of prothrombotic risk factors is not uncommon. Since pregnancy is an acquired hypercoagulable state, women harboring thrombophilia may present with clinical symptoms of vascular complications for the first time during gestation or at the postpartum period (3, 4). Combined thrombophilia also exists when inherited and/or acquired prothrombotic factors are pooled. Every combination carries a different risk of thrombosis. A scoring system, which is composed of four major categories: obstetrical history, previous thromboembolic events, family history and type of thrombophilia, can help us to stratify universally the thrombotic risk during pregnancy and peripartum and administer the appropriate antithrombotic treatment. BACKGROUND Pregnancy is considered to be an acquired hypercoagula- ble state due to increased levels of coagulation factors, de- creased levels of anticoagulants and decreased fibrinolytic activity. The gradual increase in hypercoagulability during normal pregnancy predisposes to venous thromboembolism (VTE), and to gestational vascular complications, including recurrent pregnancy loss, intrauterine- growth restriction (IUGR), eclampsia, pre-eclampsia and placental abruption. These adverse pregnancy outcomes affect up to 15% of ges- tations and are the major cause of maternal and fetal morbid- ity and mortality (3). In one study, at least one thrombophilic defect was found in 96/145 (66%) of woman with recurrent fetal loss compared to 41/145 (28%) in controls (or=5.0, 95/5 ci: 3.0-8.5 p <0.0001) (4). Inherited thrombophilia is common and can be found in 15% to 25% of Caucasian populations. Thus, a combination of thrombophilic risk factors is not rare and can be detected, regarding Israel, in up to 5% of women with pregnancy loss (4, 5). Factor V Leiden is the most common inherited mutation that is associated with increased risk of VTE. Other com- monly inherited thrombophilia type is the prothrombin (FII G20210A) mutation but also the C677T polymorphism in the methylenetetrahydrofolate- reductase gene, which results in a thermolabile variant of the enzyme predisposing to hyper- homocysteinemia. However, the most thrombogenic *Address correspondence to this author at the Thrombosis and Hemostasis