What is the role of D-dimer (D-dimer test) in diagnosing thromboembolic events during pregnancy?

D-dimer Testing in Pregnancy for Thromboembolic Events

In pregnant women with suspected thromboembolic events, D-dimer testing is not recommended as a standalone test to exclude pulmonary embolism or deep vein thrombosis due to its limited diagnostic accuracy in this population. 1, 2

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 2
• By the third trimester, D-dimer levels are above the conventional cut-off point (500 µg/L) in 99% of pregnant women 3
• This physiologic increase significantly reduces the specificity of D-dimer testing during pregnancy 4, 5

Diagnostic Accuracy in Pregnancy

• Studies have shown that D-dimer testing in pregnancy has poor diagnostic performance:
  • Sensitivity: only 73% (compared to >95% in non-pregnant patients)
  • Specificity: extremely low at 15%
  • Negative likelihood ratio: 1.8 (inadequate to rule out pulmonary embolism) 4, 2
• The American Thoracic Society/Society of Thoracic Radiology explicitly recommends against using D-dimer to exclude pulmonary embolism in pregnancy 1

Recommended Diagnostic Approach for Suspected DVT in Pregnancy

• For pregnant women with suspected DVT, initial evaluation with proximal compression ultrasound (CUS) is recommended over other tests, including D-dimer 1
• If initial proximal CUS is negative but clinical suspicion remains high, serial CUS testing is recommended 1
• For suspected iliac vein DVT (symptoms include whole leg swelling with/without flank, buttock, or back pain), additional imaging with MRI or venography may be necessary 1

Recommended Diagnostic Approach for Suspected PE in Pregnancy

• For pregnant women with suspected PE and signs/symptoms of DVT:

  • Perform bilateral compression ultrasound of lower extremities
  • If positive, begin anticoagulation without further testing
  • If negative, proceed with additional imaging 1

• For pregnant women with suspected PE without signs/symptoms of DVT:

  • Chest X-ray should be the first radiation-associated procedure
  • If CXR is normal, lung scintigraphy is recommended over CT pulmonary angiography 1

Clinical Decision Rules and Risk Assessment

• A clinical prediction model for DVT in pregnancy includes three variables:
  • Left leg symptoms (adjusted OR 44.3)
  • Calf circumference difference ≥2 cm (adjusted OR 26.9)
  • First trimester presentation (adjusted OR 63.4) 1
• With none of these criteria, DVT was not diagnosed in studied populations (0%)
• With one variable, DVT occurred in 16.4% of cases
• With two or three variables, DVT occurred in 58.3% of cases 1

Key Pitfalls to Avoid

• Do not rely on a negative D-dimer to exclude thromboembolic events in pregnant women 1, 2
• Do not assume that thromboprophylaxis with low-molecular-weight heparin prevents the physiologic increase in D-dimer during pregnancy 5
• Avoid unnecessary radiation exposure by using ultrasound as the first-line imaging test when DVT is suspected 1
• Remember that common symptoms of PE (shortness of breath, tachycardia) may be normal in pregnancy, requiring a high index of suspicion 2

Alternative Approaches Under Investigation

• Trimester-specific reference intervals have been proposed but require validation before clinical application:
  • First trimester: 169-1202 µg/L
  • Second trimester: 393-3258 µg/L
  • Third trimester: 551-3333 µg/L 3
• Concomitant use of D-dimer with clinical prediction rules (like Wells' criteria) may have some utility, but this approach requires further validation 6