What is the role of D-dimer (D-dimer test) in diagnosing thromboembolic events in a pregnant woman in her first trimester?

D-Dimer Testing in First Trimester Pregnancy

D-dimer testing has limited but not negligible utility in the first trimester for excluding venous thromboembolism (VTE), though it should never be used as the sole diagnostic test and proximal compression ultrasonography remains the recommended first-line investigation. 1, 2

Physiologic Changes in First Trimester

D-dimer levels begin rising early in pregnancy, with mean concentrations increasing from pre-conception levels of 0.43 mg/L to 0.58 mg/L in the first trimester—representing a 39% relative increase. 1 However, the first trimester represents the period when D-dimer retains its greatest potential utility, as 84% of healthy pregnant women still have normal D-dimer levels using conventional cutoffs during this early gestational period. 3

Diagnostic Performance

The sensitivity of D-dimer testing in pregnancy is acceptable (73-100% depending on the assay used), but specificity is severely limited at only 15%, resulting in a negative likelihood ratio of 1.8—inadequate for reliably excluding pulmonary embolism. 2, 4 Despite these limitations, a negative D-dimer test maintains some exclusion value, particularly in early pregnancy when physiologic elevations are less pronounced. 2, 5

Key Evidence Points:

• The SimpliRED assay demonstrated 100% sensitivity and 60% specificity in pregnancy, with only 24% false-positive rate in the first trimester (compared to 51% in third trimester). 6
• All pregnant women with confirmed thrombosis had D-dimer levels 6.7-7.6 times higher than mean reference values for their trimester. 3
• Trimester-specific cutoffs have been proposed (286 ng/mL for first trimester) to improve diagnostic accuracy. 3

Guideline-Based Recommendations

For suspected deep vein thrombosis (DVT) in first trimester, begin with proximal compression ultrasonography rather than D-dimer testing. 1, 2 The American College of Chest Physicians explicitly recommends proximal CUS over D-dimer (Grade 2C versus moderately sensitive D-dimer; Grade 1B versus highly sensitive D-dimer). 1

For suspected pulmonary embolism, the American Thoracic Society/Society of Thoracic Radiology explicitly recommends against using D-dimer to exclude the diagnosis in pregnancy. 2, 5

Clinical Algorithm for First Trimester VTE Suspicion

If DVT is suspected:

1. Perform proximal compression ultrasonography immediately as first-line test 1, 2
2. If positive: initiate therapeutic anticoagulation with LMWH 5
3. If negative but high clinical suspicion (particularly with left leg symptoms, calf circumference difference ≥2 cm, or first trimester presentation): perform serial CUS on days 3 and 7 1, 7

If pulmonary embolism is suspected:

1. Do not rely on D-dimer alone for exclusion 2, 5
2. If D-dimer is obtained and negative in first trimester: PE is less likely but cannot be completely excluded 2
3. If D-dimer is elevated: proceed to bilateral compression ultrasonography of lower extremities 2, 5
4. If ultrasound positive for DVT: treat with anticoagulation without further imaging 2
5. If ultrasound negative: proceed with appropriate chest imaging (perfusion scan or CT pulmonary angiography) 2

Critical Clinical Caveat

First trimester presentation is itself a high-risk variable for DVT (adjusted OR 63.4), meaning clinical suspicion should be heightened during this period. 1, 7 When combined with left leg symptoms or calf circumference difference ≥2 cm, the probability of DVT reaches 58.3%. 1, 7 This paradoxically makes the first trimester both the period when D-dimer is most physiologically normal AND when clinical risk assessment is most critical.

Practical Approach

If D-dimer testing is performed in the first trimester despite guideline recommendations against it, interpret results as follows:

• Negative result: Provides some reassurance but proceed with imaging if clinical suspicion remains moderate-to-high 2, 6
• Positive result: Proceed immediately to compression ultrasonography—do not use elevated D-dimer alone to diagnose VTE 2, 5
• Consider trimester-specific cutoffs (286 ng/mL for first trimester) if your laboratory has established these reference ranges 3

The fundamental principle remains: imaging with compression ultrasonography, not D-dimer testing, should guide management decisions for suspected VTE in first trimester pregnancy. 1, 2