How do you interpret D-dimer (D-dimer) results in a patient suspected of having a thrombotic disorder, such as deep vein thrombosis (DVT) or pulmonary embolism (PE), and what are the next steps in management?

D-Dimer Interpretation in Suspected Thrombotic Disorders

Primary Recommendation

In patients with suspected DVT or PE, D-dimer should only be used to exclude disease in those with low or intermediate clinical probability—a negative highly sensitive D-dimer (ELISA or equivalent) combined with low pretest probability safely rules out VTE without further imaging, while any positive D-dimer or high clinical probability mandates immediate imaging regardless of D-dimer results. 1

Clinical Probability Assessment Must Precede D-Dimer Testing

• Always calculate a validated clinical probability score before ordering D-dimer using either the Wells score or revised Geneva score to stratify patients into low, intermediate, or high probability categories 1
• The Wells score assigns points for active cancer (1 point), paralysis/recent immobilization (1 point), bedridden >3 days or major surgery within 4 weeks (1 point), localized tenderness along deep venous system (1 point), entire leg swelling (1 point), calf swelling >3 cm (1 point), pitting edema (1 point), collateral superficial veins (1 point), previous DVT (1 point), and alternative diagnosis less likely than PE (3 points) 1
• Never order D-dimer without first assessing clinical probability—this is the most common pitfall 1, 2

D-Dimer Assay Selection and Interpretation

Highly Sensitive Assays (ELISA-based)

• ELISA D-dimer assays have 97-98% sensitivity and negative likelihood ratio of 0.07, making them ideal for ruling out PE 1
• Standard cutoff is <500 ng/mL (or <0.5 μg/mL) for patients under 50 years 1, 2
• For patients >50 years, use age-adjusted cutoff: age × 10 ng/mL to improve specificity from 34% to 46% while maintaining >97% sensitivity 1, 2
• Age-adjusted cutoffs increase the proportion of elderly patients in whom PE can be excluded from 6.4% to 30% without additional false-negative findings 1, 3

Moderately Sensitive Assays

• Latex agglutination and whole blood assays have pooled sensitivity of 70-89% and are inadequate for intermediate probability patients 1
• Point-of-care assays have moderate sensitivity and should only be used in low probability patients 1

Management Algorithm by Clinical Probability

Low Clinical Probability (Wells ≤1 or Geneva 0-3)

• Order highly sensitive D-dimer as first-line test 1, 3
• If D-dimer negative: VTE excluded, no further testing needed—3-month thromboembolic risk <1% 1, 4
• If D-dimer positive: Proceed to imaging (CT pulmonary angiography for PE, compression ultrasound for DVT) 1, 3
• Negative predictive value of this strategy is 99-100% 1, 4

Intermediate Clinical Probability (Wells 2-6 or Geneva 4-10)

• Highly sensitive D-dimer can be used to exclude VTE if negative 1
• If D-dimer positive or unavailable: Proceed directly to imaging 1
• For negative CT pulmonary angiogram in intermediate probability patients with persistent clinical concern, consider additional testing (lower extremity ultrasound, repeat imaging in 5-7 days) 1

High Clinical Probability (Wells >6 or Geneva ≥11)

• Proceed directly to imaging without D-dimer testing—D-dimer has insufficient negative predictive value in this population 1
• For negative CT pulmonary angiogram in high probability patients, perform additional diagnostic testing (lower extremity ultrasound, V/Q scan, or pulmonary arteriography) before excluding VTE 1
• Even with negative multidetector CT, 5.3% of high probability patients had PE on subsequent testing 1

Critical Populations Where D-Dimer Has Limited Utility

Avoid D-Dimer Testing in These Groups

• Hospitalized patients: Specificity drops dramatically, with number needed to test rising from 3 to >10 to exclude one PE 1, 2
• Cancer patients: Specificity only 18-21%, with 29% of patients with D-dimer >5000 ng/mL having malignancy rather than VTE 1, 5
• Post-surgical patients (within 4 weeks): High false-positive rate regardless of VTE status 1, 2
• Pregnant patients: D-dimer increases progressively, reaching 0.16-1.3 μg/mL in third trimester (up to 2 μg/mL may be normal) 2
• Elderly >80 years: Specificity decreases to 10% with standard cutoffs—age-adjusted cutoffs mandatory 1, 2
• Active infection/sepsis: D-dimer elevated 94-100% of the time within 24 hours 2

Management in These Populations

• Proceed directly to imaging based on clinical probability assessment alone 5
• Active cancer automatically adds 2 points to Wells score, placing most patients in intermediate-high probability 5

Markedly Elevated D-Dimer (>2000-5000 ng/mL)

Critical Conditions to Exclude

• D-dimer >2000 ng/mL warrants direct CT pulmonary angiography even in "PE unlikely" patients due to 36% positive predictive value 2
• D-dimer 3-4× upper limit of normal (>1500-2000 ng/mL) warrants hospital admission consideration even without severe symptoms, as this indicates substantial thrombin generation and increased mortality risk 2
• D-dimer >0.5 μg/mL has 94-100% sensitivity for acute aortic dissection—if elevated with chest/back pain or syncope, obtain CT angiography immediately 2
• In COVID-19 patients, D-dimer >2.12 μg/mL associated with mortality (non-survivors: 2.12 vs survivors: 0.61 μg/mL) 2

Secondary Considerations

• Consider occult malignancy if no thrombotic source identified with D-dimer >5000 ng/mL 2
• Evaluate for DIC with complete blood count, coagulation studies, and fibrinogen levels 2

Common Pitfalls to Avoid

• Never use positive D-dimer alone to diagnose VTE—confirmation with imaging always required 3
• Never order D-dimer in high clinical probability patients—proceed directly to imaging 1
• Never skip clinical probability assessment—D-dimer without pretest probability is diagnostically useless 1, 2
• Never use moderately sensitive assays (latex agglutination) for intermediate probability patients—inadequate sensitivity of 70% 1
• Never ignore age-adjusted cutoffs in elderly patients—standard cutoffs yield 90% false-positive rate in patients >80 years 1, 2
• Never dismiss persistent symptoms despite normal imaging—consider serial imaging in 5-7 days for suspected below-knee DVT, as one-sixth extend proximally 3

Imaging Selection After Positive D-Dimer

For Suspected PE

• Multidetector CT pulmonary angiography is the imaging modality of choice 1
• Negative CT pulmonary angiogram alone excludes PE in low and intermediate probability patients 1
• V/Q scanning acceptable only if: facilities available on-site, chest X-ray normal, no significant cardiopulmonary disease, standardized reporting used, and non-diagnostic results followed by further imaging 1

For Suspected DVT

• Proximal compression ultrasound or whole-leg ultrasound 3
• If whole-leg ultrasound negative in low probability patients, no further testing needed 3
• If proximal ultrasound only performed and negative with persistent symptoms, repeat in 5-7 days 3