What is the management approach for a pregnant woman with an elevated D-dimer (D-dimer elevation)?

Management of Elevated D-dimer in Pregnant Women

For pregnant women with an elevated D-dimer, further diagnostic testing is required as D-dimer increases physiologically throughout pregnancy and cannot be used alone to rule out venous thromboembolism (VTE). 1, 2

Understanding D-dimer in Pregnancy

• D-dimer levels increase progressively throughout pregnancy, with approximately 39% relative increase in each trimester compared to the previous one 1, 3
• Mean D-dimer concentrations during pregnancy:
  • 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, 4
• By the third trimester, virtually all pregnant women (99%) have D-dimer levels above the conventional cut-off of 0.50 mg/L 4, 3
• D-dimer levels increase even more dramatically during and immediately after delivery 5, 6

Diagnostic Algorithm for Suspected VTE with Elevated D-dimer

1. Initial Assessment:

   • Despite limitations, a negative D-dimer still has some exclusion value, particularly in early pregnancy 2
   • If D-dimer is elevated, proceed with bilateral compression ultrasonography 1, 2

2. Compression Ultrasonography:

   • If ultrasound is positive for DVT: Initiate anticoagulation treatment 1, 2
   • If ultrasound is negative but clinical suspicion for PE remains: Further imaging is required 1

3. Further Imaging (if needed):

   • MRI for suspected iliac vein thrombosis (no radiation exposure) 1, 2
   • CT pulmonary angiography for suspected pulmonary embolism (preferred over ventilation-perfusion scanning due to lower fetal radiation exposure) 1
   • Both imaging modalities deliver radiation doses below dangerous levels for the fetus 1

Treatment When VTE is Confirmed

• LMWH is the drug of choice for treatment of VTE in pregnancy 1
• Dosing is weight-based:
  • Enoxaparin: 1 mg/kg body weight twice daily
  • Dalteparin: 100 IU/kg body weight twice daily 1
• Target 4-6 hour peak anti-Xa values of 0.6-1.2 IU/mL 1
• LMWH has lower risks of heparin-induced thrombocytopenia (HIT) and osteoporosis compared to unfractionated heparin 1

Prophylaxis Based on Risk Assessment

For women with elevated D-dimer but no confirmed VTE, risk assessment should guide management:

• High Risk (previous recurrent VTE, unprovoked/estrogen-related VTE, or VTE with thrombophilia/family history):

  • Antenatal prophylaxis with LMWH
  • Continue prophylaxis for 6 weeks postpartum
  • Add graduated compression stockings 1

• Intermediate Risk (≥3 risk factors or ≥2 risk factors if hospitalized):

  • Consider antenatal prophylaxis with LMWH
  • Prophylaxis for at least 7 days postpartum (longer if >3 risk factors persist)
  • Consider graduated compression stockings 1

• Low Risk (<3 risk factors):

  • Early mobilization
  • Avoid dehydration 1

Important Caveats

• The American Thoracic Society/Society of Thoracic Radiology explicitly recommends against using D-dimer alone to exclude PE in pregnancy due to low specificity (15%) 2
• D-dimer fluctuates significantly within individual pregnant women (up to 50 percentile points in 10% of women), making repeated measurements of limited clinical value 7
• D-dimer levels remain elevated postpartum, with only 79-93% of women returning to levels below 500 ng/mL by 30-45 days after delivery 6