How is D-dimer (D-dimer test) interpreted in pregnancy?

D-dimer Interpretation in Pregnancy

D-dimer testing is not reliable for excluding pulmonary embolism (PE) in pregnancy due to physiologic increases throughout gestation and should not be used as the sole diagnostic tool. 1

Physiologic Changes of D-dimer During Pregnancy

• D-dimer levels increase progressively throughout normal pregnancy, with values rising by approximately 39% in each trimester compared to the previous one 1
• Mean D-dimer concentrations during pregnancy have been reported as:
  • Pre-conception: 0.43 mg/L
  • First trimester: 0.58 mg/L
  • Second trimester: 0.83 mg/L
  • Third trimester: 1.16 mg/L 1, 2
• By the third trimester, approximately 99% of pregnant women will have D-dimer levels above the conventional cut-off point (500 µg/L) 2
• D-dimer levels peak during labor and remain elevated in the immediate postpartum period 3, 4

Diagnostic Value in Pregnancy

• A retrospective study showed D-dimer had only 73% sensitivity and 15% specificity for PE in pregnancy, with a negative likelihood ratio of 1.8, making it inadequate to rule out PE 1
• False negative D-dimer results have been documented in pregnant women with confirmed PE 1
• The American Thoracic Society/Society of Thoracic Radiology guidelines recommend against using D-dimer to exclude PE in pregnancy due to these limitations 1

Clinical Approach to Suspected PE in Pregnancy

• Despite limitations, a normal D-dimer value still has some exclusion value for PE in pregnant women, particularly in early pregnancy 1
• If D-dimer testing is performed and results are normal, it may help avoid unnecessary radiation exposure to the fetus 1
• If D-dimer is elevated (which is common in normal pregnancy):
  • Proceed to bilateral compression ultrasonography of lower extremities 1
  • A positive ultrasound finding warrants anticoagulation without further imaging 1
  • If ultrasound is negative, continue with appropriate imaging studies 1

Diagnostic Algorithm for Suspected PE in Pregnancy

1. Clinical assessment with high index of suspicion (common symptoms like dyspnea and tachycardia may be normal in pregnancy) 1
2. Consider D-dimer testing (recognizing limitations):
   • If negative (especially in early pregnancy): PE less likely but cannot be completely excluded 1
   • If positive: Proceed with diagnostic imaging 1
3. Bilateral compression ultrasound of lower extremities:
   • If positive for DVT: Treat with anticoagulation 1
   • If negative: Proceed with chest imaging 1
4. Appropriate imaging based on clinical context and local expertise (perfusion lung scan or CT pulmonary angiography) 1

Important Caveats

• D-dimer fluctuates significantly within individual pregnant women - one study found maximal fluctuation of approximately 20 percentile points in half of women, and more than 50 percentile points in 10% of women 5
• Due to this biological variation, repeated D-dimer measurements during pregnancy have no clinical utility 5
• The usefulness of D-dimer remains limited until approximately 4 weeks postpartum 4
• Some experts have proposed higher trimester-specific reference intervals:
  • First trimester: 169-1202 µg/L
  • Second trimester: 393-3258 µg/L
  • Third trimester: 551-3333 µg/L 2
  • However, these have not been validated in prospective studies of pregnant women with suspected PE 2