What is the next diagnostic step for an elderly female patient with elevated D-dimer (D-dimer) and no evidence of deep vein thrombosis (DVT) or pulmonary embolism (PE)?

From the Guidelines

The next diagnostic step for an elderly female patient with an elevated D-dimer but no evidence of DVT or pulmonary embolism would be to consider alternative causes for the D-dimer elevation, as the specificity of this test is low in elderly patients, making false positives common in this population. I recommend conducting a comprehensive evaluation for other conditions that commonly cause D-dimer elevation in elderly patients, including infection, inflammation, malignancy, and recent surgery or trauma. Specific tests should include a complete blood count with differential, comprehensive metabolic panel, C-reactive protein, and age-appropriate cancer screenings if not recently performed.

Key Considerations

• In elderly patients, D-dimer levels naturally increase with age, which reduces the specificity of this test 1.
• The Wells criteria or Geneva score can be used to reassess the pre-test probability of venous thromboembolism.
• If clinical suspicion remains despite negative initial imaging, consider alternative imaging modalities such as CT venography for DVT or V/Q scan for PE, particularly if the patient has renal insufficiency limiting contrast use.

Diagnostic Approach

• Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered 1.
• Clinicians should use age-adjusted d-dimer thresholds (age × 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted 1.
• Clinicians should not obtain any imaging studies in patients with a d-dimer level below the age-adjusted cutoff 1.

Additional Recommendations

• Remember that while an elevated D-dimer has high sensitivity for thrombotic events, its specificity is low, especially in elderly patients, making false positives common in this population.
• Consider the patient's overall clinical presentation and medical history when interpreting the results of the D-dimer test and other diagnostic evaluations.

From the Research

Next Diagnostic Steps for Elevated D-Dimer without DVT or Pulmonary Embolism

• The patient's elevated D-dimer level without evidence of deep vein thrombosis (DVT) or pulmonary embolism (PE) requires further evaluation to determine the cause of the elevated D-dimer and to rule out other potential conditions 2.
• Clinical evaluation, including assessment of clinical pretest probability (CPTP) for venous thromboembolism (VTE), likelihood of important alternative diagnoses, and probable yield of D-dimer and various imaging tests, can guide the next diagnostic steps 2.
• If the clinical pretest probability is low, a negative D-dimer assay result can exclude DVT or PE 2, 3.
• However, if the D-dimer level is elevated without evidence of DVT or PE, other potential causes of the elevated D-dimer should be considered, such as inflammation, infection, or malignancy 4, 5.
• C-reactive protein (CRP) levels can be elevated in DVT, but its diagnostic utility is limited, and it does not provide additional information for the diagnosis of DVT or PE 4, 5.
• Soluble P-selectin and high-sensitivity CRP levels can be elevated after acute DVT, but their course and diagnostic utility are influenced by treatment with anticoagulants 6.
• Further diagnostic testing, such as compression ultrasonography, impedance plethysmography, contrast venography, or magnetic resonance venography, may be necessary to evaluate for DVT or other conditions 2, 3.
• Multidetector computed tomography angiography or ventilation-perfusion scanning may be considered to evaluate for PE, especially if the clinical suspicion remains high 2, 3.