What is the significance of elevated D-dimers (D-dimer test) in pregnancy?

D-Dimer in Pregnancy: Clinical Significance and Interpretation

Physiologic Elevation During Pregnancy

D-dimer levels increase progressively throughout normal pregnancy, making standard cutoff values unreliable for excluding venous thromboembolism, particularly in the second and third trimesters. 1

• D-dimer rises by approximately 39% with each advancing trimester compared to the previous one 2
• Only 22% of women in the second trimester and 0% in the third trimester have D-dimer levels below the conventional 0.50 mg/L cutoff 3
• By the third trimester, 99% of healthy pregnant women have D-dimer levels above 500 µg/L 4
• Trimester-specific reference ranges have been established: first trimester 169-1202 µg/L, second trimester 393-3258 µg/L, and third trimester 551-3333 µg/L 4

Limited Diagnostic Utility for Pulmonary Embolism

The American Thoracic Society/Society of Thoracic Radiology explicitly recommends against using D-dimer to exclude pulmonary embolism in pregnancy due to poor test performance. 2

• A retrospective study demonstrated only 73% sensitivity and 15% specificity for PE in pregnancy, with a negative likelihood ratio of 1.8—inadequate to rule out disease 2
• The physiologic elevation during pregnancy severely limits the test's specificity, leading to excessive false-positive results 1
• A normal D-dimer retains some exclusion value in early pregnancy but becomes essentially useless in the third trimester when using standard cutoffs 1, 3

Recommended Diagnostic Approach for Suspected VTE in Pregnancy

When D-dimer Testing May Still Be Considered

• In the first trimester, a normal D-dimer may help avoid unnecessary radiation exposure to the fetus 2
• The European Society of Cardiology guidelines acknowledge that normal D-dimer has the same exclusion value in pregnant women as other patients, though it is found more rarely 1

Algorithmic Approach to Suspected Pulmonary Embolism

If D-dimer testing is performed and elevated (which is expected in most pregnant women): 1

1. Proceed immediately to bilateral lower extremity compression ultrasonography 1, 2

   • If proximal DVT is detected, initiate anticoagulation treatment—thoracic imaging becomes unnecessary 1
   • DVT is left-sided in 85% of pregnancy cases due to compression of the left iliac vein 1

2. If compression ultrasound is negative, continue with thoracic imaging 1

   • Perfusion lung scintigraphy may be preferred over CT angiography when available, as it delivers less radiation to maternal breast tissue 1
   • Ventilation scanning is usually unnecessary as chest X-ray is typically normal 1
   • CT pulmonary angiography is acceptable—both modalities are safe for ruling out PE in pregnancy 1

Approach to Suspected Deep Vein Thrombosis

For suspected DVT, initial evaluation with proximal compression ultrasound is recommended over D-dimer testing. 2

• A clinical decision rule incorporating three variables provides risk stratification: left leg presentation, ≥2 cm calf circumference difference, and first trimester presentation 1, 2
• If initial compression ultrasound is negative but suspicion remains high, perform serial ultrasound evaluations at days 0,3, and 7 (negative predictive value 99.5%) 1
• For suspected isolated pelvic or iliac vein thrombosis, magnetic resonance venography should be considered 1, 2

Critical Clinical Pitfalls

• Do not rely on elevated D-dimer alone to diagnose VTE in pregnancy—the test lacks specificity due to physiologic elevation 1
• Do not use a negative D-dimer in the third trimester to exclude VTE—virtually all healthy pregnant women exceed standard cutoffs 3, 4
• Repeated D-dimer measurements during pregnancy are of no clinical value due to large biological fluctuation (up to 50 percentile points in 10% of women) 5
• D-dimer levels increase dramatically after delivery (1 to >10 times normal range), further limiting postpartum interpretation 6

When Imaging Should Be Pursued Directly

In pregnant women with high clinical suspicion for PE, proceed directly to diagnostic imaging without D-dimer testing. 1

• The risk of missing a potentially fatal diagnosis outweighs concerns about fetal radiation exposure 1
• All radiological tests fall well below the 50 mSv danger threshold for fetal injury 1
• Erroneously diagnosing PE unnecessarily exposes mother and fetus to anticoagulation risks and impacts delivery planning and future pregnancy management 1