Factor V Leiden and Recurrent Miscarriage
Prospective Outcome of Untreated Pregnancies
Some cases of recurrent first trimesteric miscarriage and later pregnancy complications have a thrombotic basis.
Factor V Leiden is a common thrombophilic mutation (About 4% to 7% of the population is heterozygous for Factor V Leiden. Around 0.06% to 0.25% of the population is homozygous for Factor V Leiden).
Pregnancy is a hypercoagulable state secondary to (i) an increase in coagulation factors, (ii) a reduction in naturally occurring anticoagulants and (iii) an impairment of fibrinolysis. The evolutionary advantage of these changes is thought to be stabilization of haemochorial placentation and reduction in post-partum blood loss.
Since antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies), an acquired thrombophilic defect, have been established as an important and treatable cause for pregnancy loss at all gestational ages, the potential role that other thrombophilic defects may play in adverse pregnancy outcome is now clearly proved. One such thrombophilic defect is Factor V Leiden (a common mutation (G A) at nucleotide position 1691 in the Factor V gene), which is associated with a significant increased risk for systemic venous thrombosis. Factor V Leiden has also been reported in association with uteroplacental thrombosis.
The live birth rate was significantly lower amongst women with a history of recurrent early miscarriage who carried the Factor V Leiden allele compared with that amongst those with a normal Factor V genotype.
There has consequently been a shift in emphasis from the restrictive concept of single, dominant causes of thrombosis to emphasizing the potential role of multiple, inherited risk factors. This concept of the aetiology of systemic thrombosis is also likely to be applicable to placental thrombosis. 52% of women with an obstetric complication (pre-eclampsia, placental abruption or intrauterine growth restriction) carried one or more of three thrombophilic mutations (Factor V Leiden, prothrombin G2021A or methylenetetrahydrofolate reductase C677T) these mutations were also present in 17% of women with normal pregnancies and a successful, uncomplicated live birth at term. Clearly not all women who carry a thrombophilic mutation suffer a pregnancy loss and perhaps it is those who carry multiple thrombophilic defects who are at greatest risk.
Attention should be directed at screening women with recurrent miscarriage associated with placental thrombosis for Factor V Leiden and other thrombophilic disorders and a policy of targeted heparin and/or low dose aspirin thromboprophylaxis during future pregnancies.
Identification of Factor V, Prothrombin and MTHFR gene mutations by Multiplex PCR and Reverse Hybridization is done in Saridar Lab and the result will be after 48 hours.