What does a D-dimer (Deep vein thrombosis/pulmonary embolism marker) test check for?

What Does D-Dimer Check For?

D-dimer is a fibrin degradation product that measures active blood clot formation and breakdown in the body, serving primarily as a highly sensitive rule-out test for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). 1

Primary Clinical Use

D-dimer testing functions as a rule-out test, not a rule-in test, with high sensitivity (96%) but poor specificity (35%) for VTE. 1 This means:

• A negative D-dimer effectively excludes VTE in patients with low clinical probability, with a negative predictive value of 99-100%, making it safe to withhold anticoagulation without further testing. 2
• A positive D-dimer cannot diagnose VTE and must always be followed by confirmatory imaging (ultrasound for DVT, CT pulmonary angiography for PE). 1, 2

What D-Dimer Measures Physiologically

D-dimer is a specific fibrin degradation product released when crosslinked fibrin (formed during blood clot formation) is broken down by plasmin during fibrinolysis. 3 It has a half-life of approximately 16 hours in circulation. 3 Elevated levels indicate both:

• Active coagulation (clot formation)
• Subsequent fibrinolysis (clot breakdown)

Appropriate Clinical Application Algorithm

For Suspected DVT or PE:

Low Clinical Probability (≤10%): 1

• Order highly sensitive D-dimer test first
• If negative: VTE excluded, no further testing needed (3-month thromboembolic risk <1%)
• If positive: Proceed to imaging (ultrasound for DVT, CTPA for PE)

Intermediate Clinical Probability (~25%): 1

• Highly sensitive D-dimer can safely exclude PE when negative
• If positive: Proceed to imaging

High Clinical Probability (≥40%): 1, 3

• Skip D-dimer testing entirely - proceed directly to imaging
• D-dimer wastes time and resources in this population

Conditions That Cause Elevated D-Dimer

Thrombotic Causes:

• Pulmonary embolism (most common, 32% of extremely elevated D-dimers) 4
• Deep vein thrombosis 1
• Acute aortic dissection (sensitivity 94-100% when measured within 24 hours) 3
• Cerebral venous thrombosis 3

Non-Thrombotic Causes:

• Sepsis and severe infection (24% of extremely elevated D-dimers) 4
• Active malignancy (29% of extremely elevated D-dimers) 4
• Disseminated intravascular coagulation (DIC) 3
• Recent trauma or surgery (24% of cases) 4
• Acute myocardial infarction 3
• Pregnancy (physiologically elevated) 3
• Advanced age (naturally increases with age) 3
• Recent thrombolytic therapy 3

Critical finding: 89% of patients with extremely elevated D-dimer (>5000 μg/L or >10× normal) have VTE, sepsis, and/or cancer. 4

Important Limitations and Populations Where D-Dimer Has Poor Utility

D-dimer testing has severely limited diagnostic value in: 1, 2

• Hospitalized patients (high false-positive rate)
• Post-surgical patients
• Pregnant women (though negative D-dimer still excludes PE) 3
• Cancer patients
• Patients with active infection or sepsis
• Elderly patients >80 years (specificity drops to only 10%) 1

Age-Adjusted Interpretation

For patients >50 years old, use age-adjusted cutoffs (age × 10 μg/L or ng/mL) to improve specificity while maintaining sensitivity >97%. 1, 2 This approach increases the proportion of elderly patients in whom PE can be safely excluded from 6.4% to 30% without additional false-negative findings. 1

Critical Pitfalls to Avoid

• Never use positive D-dimer alone to diagnose VTE - imaging confirmation is mandatory before starting anticoagulation. 1, 2
• Never order D-dimer in high clinical probability patients - it delays definitive imaging and wastes resources. 2
• Never dismiss extremely elevated D-dimer (>5000 μg/L) as nonspecific - this warrants aggressive investigation for VTE, sepsis, or malignancy. 4
• Do not order D-dimer in hospitalized or post-surgical patients where false-positives are extremely common. 1
• Remember that D-dimer levels decline over time from symptom onset, potentially causing false-negatives in delayed presentations. 3

Assay Selection Matters

Highly sensitive assays (ELISA-based, ≥95% sensitivity) are validated for ruling out VTE in low and intermediate probability patients. 2 Moderately sensitive assays (85-90% sensitivity) are safe only for low clinical probability patients. 2 Know which assay your institution uses to ensure accurate interpretation. 1