Maternal Factor V Leiden Mutation Is Associated With HELLP Syndrome in Caucasian Women

Fewer than 1% of live births are complicated by a life-threatening form of preeclampsia known as HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. About 15% of women with eclampsia or preeclampsia exhibit all aspects of HELLP syndrome, signifying an elevated risk of perinatal morbidity and mortality for both the fetus and mother. Evidence is increasing that hypertensive complications of pregnancy are associated with inherited or acquired thrombophilias. Using a case-control design, the investigators retrospectively estimated the prevalence of three inherited thrombophilic mutations (factor V Leiden, the prothrombin 20210G>A mutation, the methylenetetrahydrofolate reductase [MTHFR] 677C>T polymorphism) in 71 Caucasian mother-child pairs with HELLP syndrome and 79 control pairs with uncomplicated pregnancies. The mutations were genotyped using LightCycler technology. Maternal heterozygosity for factor V Leiden was significantly more prevalent in the HELLP group than in the control group. The odds ratio was 4.45, with a 95% confidence interval of 1.31–15.31. In contrast, no significant association with HELLP syndrome was observed for either the maternal prothrombin mutation or the MTHER polymorphism. The fetal genotype was not associated with HELLP syndrome for any of the three mutations. No differences were found when analyzing gene-gene interactions or genotype-phenotype correlation with regard to clinical parameters or perinatal outcomes. The clinical variables examined included gestational age at delivery, birth weight, systolic and diastolic blood pressure, the platelet count, liver enzyme levels, and hemolysis. These results affirm that women who are heterozygous for factor V Leiden, one of the most common inherited thrombophilias, are at increased risk of developing HELLP syndrome. Gene-gene interactions appear not to have major influence on the role of thrombophilic mutations in the causality of HELLP syndrome.