Leiden Factor V and Pregnancy: Research Review

While pregnant, a person’s risk for blood clots in their veins (venous thromboembolism) increases 5- to 6-fold. If they have hereditary thrombophilia, that risk can increase more than 30-fold. Additionally, thrombophilia increases the chance of blood clots in the placenta, which can increase the likelihood of pregnancy loss.

Factor V has an important role in blood clot formation. The Leiden mutation, or “A” allele, causes factor V to remain active longer, which increases the risk of thrombophilia and pregnancy loss. This test determines if the patient carries the higher risk “A” allele.

Physiology

Factor V (Leiden) mutation 1691 is a common point mutation G→A that causes a resistance of Factor V protein degradation by the activated protein C (APC).

This mutation is associated with increased risk of venous thrombosis (increased risk of developing blood clots) and accounts for many cases of reccurent pregnancy losses^1-2.

While the mutation is present in 5% of the Caucasian women population³, most people with factor V Leiden will not develop abnormal clots.

Nevertheless, this mutation is responsible for 20-25% of the inherited venous thrombosis cases⁴.

Heterozygous individuals (G/A) have 3-8 times more risk of developing thrombosis than the normal population⁵ and homozygous individuals (A/A) have 50 to 100 times greater risk for thrombosis⁶.

Women carrying the factor V Leiden mutation, who are pregnant or on estrogen therapy, have a 30 times higher risk for venous thrombosis⁷.

Published clinical data

Studies comparing Factor V genotype between fertile controls and women experiencing reccurent pregnancy losses (RPL) showed an increased incidence of the 1691 A allele in infertile patients.
The A allele frequency of Factor V Leiden was shown to be significantly higher in RPL patients (7.5%) as compared to fertile controls (1.88%)⁸.

Depending on the studies, the A allele frequency varies from 8 to 32% in RPL patients as compared to 4 to 10% in the fertile control population^9-10.

Further, the presence of the A allele was found to place a patient with RPL at a four times higher risk for another miscarriage¹¹ while a meta-analysis estimates that this risk doubles in RPL patients¹².

Hypercoagulability due to thrombophilic factors is a key event leading to a decreased placental perfusion which induces symptoms of pre-eclampsia.

A meta-analysis including thirty-one studies with 7,522 patients showed that the factor V Leiden polymorphism (1691 G→A) is associated with a 2-fold increased risk for all and severe preeclampsia¹³. Another meta-analysis comparing healthy pregnancy to pre-eclamptic pregnancy showed that factor V Leiden polymorphism (1691 G→A) is associated with a +87% increased risk for pre-eclampsia¹⁴.
Risk for pre-eclampsia has been estimated to double in carrier patients for the allele 1691 A allele¹².