How are modified D-dimer (D-dimer) values interpreted in pregnancy?

D-dimer Interpretation in Pregnancy

D-dimer levels increase progressively throughout normal pregnancy and cannot be reliably used with standard non-pregnant cutoffs, particularly after the first trimester, requiring either higher pregnancy-specific thresholds or alternative diagnostic approaches when evaluating for venous thromboembolism. 1

Physiologic Changes During Pregnancy

D-dimer concentrations rise substantially as pregnancy advances, with approximately 39% relative increase in each successive trimester 2, 3:

• First trimester: 0.11-0.40 μg/mL (mean 0.58 mg/L) 1, 3
• Second trimester: 0.14-0.75 μg/mL (mean 0.83 mg/L) 1, 3
• Third trimester: 0.16-1.3 μg/mL (mean 1.16 mg/L), with 99% of normal pregnant women exceeding the standard 0.50 mg/L cutoff 1, 4
• Upper limit in third trimester: Up to 2.0 μg/mL can still represent normal pregnancy 1

Critical Limitation for Pulmonary Embolism Diagnosis

The American Thoracic Society/Society of Thoracic Radiology explicitly recommends against using D-dimer to exclude pulmonary embolism in pregnancy. 2, 3 This strong recommendation stems from poor test performance:

• Sensitivity: Only 73% (inadequate for safe exclusion) 2
• Specificity: Only 15% (extremely high false-positive rate) 2
• Negative likelihood ratio: 1.8 (insufficient to rule out disease) 2

The standard D-dimer cutoff of 0.50 mg/L has essentially no utility in the third trimester, as virtually no normal pregnant women fall below this threshold 5.

When D-dimer Testing May Still Have Limited Value

Despite these limitations, D-dimer retains some exclusion value in specific circumstances 1, 2:

• Early pregnancy (first trimester): Normal D-dimer values may help avoid unnecessary fetal radiation exposure 2, 3
• Low clinical probability patients: Combined with clinical prediction rules, a negative D-dimer in early pregnancy provides modest reassurance 2

However, clinicians must recognize that a negative D-dimer cannot completely exclude PE even in these scenarios 2.

Proposed Pregnancy-Specific Thresholds

Research suggests higher cutoffs may improve diagnostic performance, though these require prospective validation 6, 7:

• For suspected PE: Cutoff of 1,447 μg/L (sensitivity 87.5%, specificity 63%) 7
• Combined with Wells criteria:
  • PE unlikely: 1,447 μg/L cutoff 7
  • PE likely: 1,962 μg/L cutoff 7
• For suspected DVT: Higher trimester-specific cutoffs (62-79% specificity while maintaining 80-100% sensitivity) 6

Recommended Diagnostic Algorithm for Suspected PE in Pregnancy

When PE is suspected, proceed directly to objective testing rather than relying on D-dimer 2, 3:

1. Clinical assessment: Recognize that dyspnea and tachycardia may be normal pregnancy findings 2

2. If D-dimer is obtained and elevated (or not performed):

   • Proceed immediately to bilateral compression ultrasonography of lower extremities 2, 3
   • If ultrasound positive for DVT: Initiate anticoagulation without further imaging 2, 3
   • If ultrasound negative: Proceed to chest imaging (CT pulmonary angiography or ventilation-perfusion scan) 2, 3

3. Do not withhold imaging based on negative D-dimer alone 2, 3

Interpretation of Markedly Elevated D-dimer

D-dimer values several-fold above the upper range of normal for pregnancy should raise concern for coagulopathy or thrombosis 1:

• Values substantially exceeding 2.0 μg/mL warrant careful evaluation 1
• In COVID-19 coagulopathy, non-survivors had D-dimer levels of 2.12 μg/mL (range 0.77-5.27 μg/mL) compared to 0.61 μg/mL in survivors, though 2.0 μg/mL can still be normal in pregnancy 1
• Consider pregnancy-modified DIC scoring when coagulopathy is suspected 1

Common Pitfalls to Avoid

• Do not use the standard 0.50 mg/L cutoff in the second or third trimester—it will be positive in virtually all normal pregnancies 4, 5
• Do not rely on D-dimer alone to exclude PE at any stage of pregnancy, as sensitivity is inadequate 2, 3
• Pregnancy decreases D-dimer specificity similar to other conditions like malignancy, advanced age, and hospitalization 1
• Do not delay objective imaging when clinical suspicion is moderate to high, regardless of D-dimer results 2, 3