How is a D-dimer (D-dimer) level interpreted and managed in pregnancy?

D-dimer Interpretation and Management in Pregnancy

D-dimer levels physiologically increase throughout pregnancy, making conventional cut-off values unsuitable for ruling out venous thromboembolism (VTE) in pregnant women. 1, 2

Normal D-dimer Values During Pregnancy

D-dimer levels progressively increase throughout pregnancy due to physiological changes:

• First trimester: 0.11-0.40 μg/mL 1, 2
• Second trimester: 0.14-0.75 μg/mL 1, 2
• Third trimester: 0.16-1.3 μg/mL (up to 2.0 μg/mL can still be normal) 1, 2

Studies show that by the third trimester, 99% of pregnant women have D-dimer levels above the conventional cut-off point of 500 μg/L (0.5 μg/mL) 3, making standard thresholds ineffective.

Diagnostic Algorithm for Suspected VTE in Pregnancy

1. Clinical assessment and D-dimer testing:

   • Measure D-dimer in patients with suspected pulmonary embolism (PE) 1
   • A negative D-dimer has the same exclusion value for PE in pregnant women as in non-pregnant patients 1
   • However, negative results are less common due to physiological increases 1

2. If D-dimer is negative:

   • VTE is unlikely 1
   • Anticoagulation is not warranted 1

3. If D-dimer is positive:

   • Proceed to bilateral compression ultrasonography of lower limbs 1
   • If ultrasonography is positive → anticoagulation treatment is indicated 1
   • If ultrasonography is negative → further testing is required 1

4. Further imaging if needed:

   • Consider perfusion lung scintigraphy (if chest X-ray is normal) 1
   • CT pulmonary angiography if scintigraphy is inconclusive 1

Clinical Considerations and Pitfalls

Biological Variation

• Significant biological fluctuation occurs within individual pregnant women 4
• D-dimer can fluctuate by approximately 20 percentile points in half of pregnant women 4
• In 10% of women, fluctuations exceed 50 percentile points 4
• Due to this variation, repeated D-dimer measurements have limited clinical utility 4

Postpartum Period

• D-dimer levels are markedly elevated immediately after delivery 5
• All measurements typically remain above 500 ng/mL through day 3 postpartum 5
• A sharp decrease occurs between day 1 and day 3, followed by a slight increase at day 10 5
• D-dimer returns to non-pregnant levels in most women (79-93%) by 4-6 weeks postpartum 5, 6

Treatment Considerations

• If VTE is confirmed, treatment is based on heparin anticoagulation 1
• Low molecular weight heparin (LMWH) is the preferred treatment during pregnancy 1
• Weight-adjusted dosing should be used 1
• Heparin does not cross the placenta and is not found in breast milk in significant amounts 1

Special Situations

Twin Pregnancies

• D-dimer levels are not significantly different between singleton and twin pregnancies in the first trimester 7
• In the third trimester, D-dimer levels are higher in twin pregnancies (3.7 ± 2.5 μg/mL) compared to singleton pregnancies (2.2 ± 1.6 μg/mL) 7

Markedly Elevated D-dimer

• D-dimer levels several-fold above the upper range of normal for pregnancy should be considered indicative of coagulopathy 1
• When D-dimer exceeds 3.2 μg/mL in the third trimester, closer monitoring may be warranted 7

By understanding the physiological changes in D-dimer levels during pregnancy and following a systematic diagnostic approach, clinicians can appropriately interpret results and manage suspected VTE in pregnant women, ultimately improving maternal and fetal outcomes.