What is the approach to a false positive D-dimer (Deep Vein Thrombosis/DVT and Pulmonary Embolism/PE biomarker) result?

Managing False Positive D-dimer Results in DVT/PE Evaluation

When evaluating a patient with a positive D-dimer test but low clinical probability for DVT/PE, proceed with imaging studies such as CT pulmonary angiography to definitively rule out thromboembolism rather than dismissing the result as a false positive. 1, 2

Understanding D-dimer Test Characteristics

D-dimer testing has excellent sensitivity (93-96%) but poor specificity (39-51%) for venous thromboembolism (VTE), making false positive results common 1. This test characteristic profile means:

• Negative predictive value is high (>99%) in low-risk patients
• Positive predictive value is low, especially in certain populations
• False positives occur frequently and require further evaluation

Factors Associated with False Positive D-dimer Results

Several conditions and patient characteristics are associated with elevated D-dimer levels in the absence of VTE:

• Advanced age: D-dimer specificity decreases significantly with age 1, 2
• Pregnancy: Particularly beyond the first trimester 1
• Cancer: Significantly reduces specificity (as low as 18-21%) 1
• Infection/inflammation: Increases D-dimer levels independent of VTE 2
• Recent surgery or trauma: Can elevate D-dimer levels 3
• Hospitalization: Inpatients frequently have elevated D-dimer for reasons other than VTE 2

Algorithmic Approach to Managing False Positive D-dimer Results

Step 1: Risk Stratification

• Use validated clinical prediction tools (Wells score or revised Geneva score) to determine pre-test probability 2, 3
• Document specific risk factors for VTE (immobilization, surgery, cancer, prior VTE, etc.)

Step 2: Interpret D-dimer Result Based on Risk Category

• Low clinical probability + positive D-dimer: Proceed to imaging (CTPA) 1, 2
• Intermediate clinical probability + positive D-dimer: Proceed to imaging (CTPA) 1, 2
• High clinical probability: D-dimer testing not recommended; proceed directly to imaging 1, 2

Step 3: Consider Age-Adjusted D-dimer Cutoffs

• For patients over 50 years: Use age-adjusted cutoff (age × 10 ng/mL) instead of fixed 500 ng/mL value 2
• This approach improves specificity without compromising sensitivity

Special Considerations

Pregnant Patients

• D-dimer has very poor specificity in pregnancy (as low as 6-23%) 1
• A negative D-dimer cannot safely rule out PE in pregnant women (sensitivity only 73%) 1
• Proceed directly to appropriate imaging studies in pregnant patients with suspected VTE

Post-Trauma Patients

• D-dimer may be falsely negative in early post-trauma phase (within first 4 days) 4
• Clinical suspicion should override negative D-dimer results in recently injured patients

Pitfalls to Avoid

1. Dismissing positive D-dimer results in low-risk patients without confirmatory imaging
2. Using D-dimer in high-risk patients where it has limited utility due to high false negative rates 1, 2
3. Failing to use age-adjusted cutoffs in elderly patients, leading to excessive false positives 2
4. Relying on D-dimer in hospitalized patients where it excludes PE in <10% of cases 2
5. Using less sensitive D-dimer assays for patients with intermediate probability 2

Diagnostic Pathway When D-dimer is Positive

When D-dimer is positive in a patient with low or intermediate clinical probability:

1. CT pulmonary angiography (CTPA) is the first-line imaging test 1, 2
2. If CTPA is contraindicated, consider V/Q scan (especially in younger patients to reduce radiation) 2
3. Compression ultrasound of lower extremities may be considered if finding a DVT would change management 1, 2

Remember that while false positive D-dimer results are common, the consequences of missing a PE (significant morbidity and mortality) outweigh the risks of additional imaging in most cases.