Challenges in the evaluation of D-dimer and fibrinogen levels in pregnant women

Thromb Res. 2013 Apr;131(4):e183-7. doi: 10.1016/j.thromres.2013.02.005. Epub 2013 Mar 5.


Introduction: Normal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. The aim of the study was to follow the changes of haemostatic parameters and to establish gestational age-specific reference intervals during normal pregnancy.

Materials and methods: Blood samples of 83 pregnant women were collected at gestational weeks 16, 26 and 36. Fibrinogen, D-dimer, and C-Reactive Protein (CRP) were examined. Reference intervals were calculated for fibrinogen, D-dimer tests with two different methods (mean±2 SD or median and 2.5th and 97.5th percentiles with 90% confidence intervals).

Results: fibrinogen and D-dimer increased progressively throughout pregnancy. Mean fibrinogen levels were higher than the maximum of the conventional reference interval, already in the 16th week of pregnancy. D-dimer levels were at or above the conventional cutoff point (250ng/mL) throughout the pregnancy in 42% of pregnant women, while in the 36th week 98% of them displayed elevated D-dimer levels. CRP did not increase in normal pregnancy.

Conclusions: There seems to be an emerging need to reconsider fibrinogen and D-dimer values from a different aspect in pregnancy compared to non-pregnant reference intervals. New reference ranges are suggested to be established in pregnancy.

MeSH terms

  • Adult
  • Biomarkers / blood
  • C-Reactive Protein / metabolism*
  • Cohort Studies
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Fibrinogen / metabolism*
  • Gestational Age
  • Humans
  • Pregnancy / blood*
  • Pregnancy Complications / blood


  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Fibrinogen
  • C-Reactive Protein