Activated Protein C Resistance (FV:Q506) and Pregnancy

Abstract

SummaryActivated protein C (APC) resistance, due to a point mutation in the factor V gene (FV:Q506), is a major risk factor for venous thromboembolism. To determine the prevalence of APC resistance in a large series of pregnant women, and to elucidate its obstetric consequences, we performed a prospective study in Malmö, Sweden, comprising 2,480 women enrolled in early pregnancy. The presence of APC resistance (the FV:Q506 allele) was determined. The women were interviewed about their medical histories including venous thromboembolic events (VTE) in relatives. The outcome variables were the VTE rate, intrapartum blood loss, and the prevalence of selected pregnancy complications such as fetal loss, pre-eclampsia, and intrauterine growth retardation.The overall prevalence of APC resistance was 11% (270/2480). The APC-resistant subgroup did not differ significantly from the non-APC-resistant subgroup in terms of pregnancy complications, but was characterized by an 8-fold higher risk of VTE (3/270 vs. 3/2210), a lower rate of profuse intrapartum haemorrhage (3.7% vs. 7.9%) (p = 0.02), and less intrapartum blood loss (340 ml vs. 361 ml) (p = 0.04). Despite the high prevalence of APC resistance in this series of gravidae (11%), its presence was unrelated to adverse pregnancy outcome apart from an 8-fold increased risk of VTE.

The effect of low molecular weight heparin (dalteparin) on duration and initiation of labour

“…This finding supports several previous clinical studies where high body weight or high BMI has been classified as independent risk factor for VTE [13,23]. In Sweden, we consider initial BMI [ 28 as an independent risk factor with 5-fold increased risk included in the recommended risk assessment algorithm [11,24].…”

“…There have been suggestions that thrombophilias are related to increased risk of obstetric complications in case-control studies. In large cohorts a prevalent thrombophilia like factor V Leiden has not been significantly related to obstetric complications or prematurity [13,21,22]. To the best of our knowledge women with prior VTE have not been related to premature delivery in large series.…”

“…Preterm delivery was defined as delivery at less than 37 completed weeks of gestation. Gestational age is usually estimated by ultrasonographic measurements of biparietal diameter and femur length in 98% of cases, and from the date of the last menstrual period in the remaining 2% [13].…”

Postpartal Right Ventricular Thrombosis

“…Factor V Leiden is present in 3-15% of the general Caucasian population and in about 15-20% of individuals with thrombosis [7,8]. As for Leiden factor V, heterozygous women have a five to ten times higher risk of thrombosis while homozygous women carry a ten to 75 times higher risk.…”

Genetics in the context of thrombophilia

“…The high prevalence of factor V Leiden among Caucasians suggests that there may be a survival advantage associated with the heterozygous state-a concept that also holds true in other disorders, such as sickle cell trait, which is protective for malaria. It has been speculated that a mild hypercoagulable state may reduce mortality from bleeding associated with childbirth or trauma [5] and this theory has been supported by some research [6][7][8], although it is yet to be conclusively confirmed.…”