INTRODUCTION
Pregnancy is a hypercoagulable state secondary to an increase in coagulation factors, a reduction in naturally occurring anticoagulants, and impairment of fibrinolysis. The evolutionary advantage of these changes is thought to be stabilization of hemochorial placentation and reduction in post-partum blood loss.(1)
Since 1965 substantial progress has been made in the identification and understanding of inherited hypercoagulable disorders that promote thrombosis, collectively termed inherited thrombophilia. These include the factor V Leiden (FVL), methylenetetrahydrofolate reductase (MTHFR), and prothrombin mutations.(2)
Although thrombophilia was initially linked to various pregnancy outcomes, most accepted associations have been refuted. The American College of obstetricians and gynecologists (2013) believes that there is not a definitive causal link between these thrombophilia and adverse pregnancy outcomes in general, and abortion in particular.(3)
Pregnancy losses were divided into preclinical, first trimester clinical, and second trimester. A meaningfully increased rate of preclinical pregnancy failure in Leiden mutation carriers was found than in no activated protein C deficiency patients.(4)
The FVL and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debate whether a mutation in the gene encoding MTHFR, an enzyme involved in homocysteine metabolism, A study revealed that increases the risk of venous thrombosis. The relative risks of late fetal loss in carriers of factor V were 3.2. Thirteen percent of the women whose fetuses died and 20 percent of the control women were homozygous for the mutation in the MTHFR gene.(5)
FVL carriage has consistently been shown to increase the risk of early-onset gestational hypertension and HELLP syndrome (Hemolysis, Elevated Liver enzymes, low platelets) in pregnancy. Maternal carriage of FVL is also associated with severe placental abruption and fetal growth disturbance.(6)
Pro-thrombophilic factors have also been proposed as one of the major causes of recurrent miscarriage (RM). In fact, some genetic polymorphisms of prothrombin (FII G 20210A), Factor FVL, and MTHFR, C677T genes were strongly associated with RM. These factors of inherited thrombophilia disturb normal placental vascularization and development leading to fetal growth restrictions, pregnancy failure, placental abruption, and therefore miscarriages or stillbirth.(7)
Another cause of miscarriages is inherited thrombophilia following damage to the maternal factor V gene G1691A (Leiden mutation) and prothrombin gene (G20210A mutation). These alterations are well studied and the test is part of the routine diagnostics of recurrent miscarriages. In the case of factor V, both the Leiden mutation G1691A and the T1328C mutation appear to be important in the pathogenesis of RM, mainly in cases observed before the 7th week of gestation.(8)
The most common causes of inherited thrombophilia are polymorphisms in genes encoding factor V, prothrombin (factor II), factor VII, MTHFR, and plasminogen activator inhibitor, while protein C, protein S and ant thrombin deficiency is less common.(9)
The finding of a link between FVL carrier state and early RPL would have significant implications for clinical practice, as it would provide a scientific rationale for screening for FVL mutation and targeted thromboprophylaxis in affected women.(10)