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)