Gestation-specific D-dimer reference ranges: A cross-sectional study

Objective To establish a gestation-specific reference range for D-dimer in healthy pregnant women with a singleton pregnancy using the Auto-Dimer assay. Design Cross-sectional study Setting Cork University Maternity Hospital, Ireland. Population Healthy pregnant women attending for routine antenatal care. Methods Simultaneous-quantile regression was performed to construct a median, 5th percentile, and 95th percentile, model of normal pregnancy D-dimer concentration versus gestational week, ranging from week 6 to 42. Additionally, pair-wise Mann-Whitney U-tests were performed to compare distributions of D-dimer concentrations for each of the four discrete gestational sampling windows with the distribution of D-dimer concentrations 48 hours postpartum. Main outcome measures D-dimer concentrations (ng/ml) during normal gestation (approximately week 6 to week 42). Results Seven hundred and sixty healthy pregnant women were investigated between gestational age week 5 and 48 hours postpartum. There was a clear steady increase in median D-dimer concentrations over the complete gestational period. Additionally, the 95th centile estimates for all gestational time-points were above the accepted non-pregnancy normal cut-off concentration (224 ng/ml). The results of the Mann-Whitney U-tests suggested that the long-term postnatal return to normal D-dimer concentrations begins in the immediate postpartum period. Conclusions We found that there is a continuous increase in D-dimer concentrations across all gestations. This research is potentially beneficial to future diagnosis of venous thromboembolism (VTE) in pregnancy using the new recommended 95th centile potential cut-offs. Possible further investigation involves an observational study comparing D-dimer concentrations in women with proven DVT with those that don't, generating likelihood ratios.