D-Dimer in Acute Aortic Syndromes
In patients with low or intermediate clinical probability of acute aortic syndrome, a negative D-dimer (<500 ng/mL) measured within 24 hours of symptom onset effectively rules out the diagnosis, but D-dimer testing should NOT be performed in high-risk patients (risk score 2-3) who require immediate imaging regardless of biomarker results. 1, 2
Risk Stratification Framework
The initial approach hinges on calculating a clinical probability score (0-3 points) based on three categories 1:
High-risk conditions (1 point each):
- Marfan syndrome or connective tissue disease
- Family history of aortic disease
- Known aortic valve disease or thoracic aortic aneurysm
- Previous aortic manipulation or cardiac surgery 1
High-risk pain features (1 point each):
- Abrupt onset
- Severe intensity
- Ripping or tearing quality 1
High-risk examination features (1 point each):
- Pulse deficit or systolic blood pressure difference
- Focal neurological deficit with pain
- New aortic diastolic murmur with pain
- Hypotension or shock 1
D-Dimer Testing Algorithm
When to Use D-Dimer
Low probability (score 0-1): Perform D-dimer testing alongside transthoracic echocardiography and chest X-ray 1. A negative D-dimer (<500 ng/mL) rules out acute aortic dissection with a negative likelihood ratio of 0.07 when measured within 24 hours of symptom onset 3.
Intermediate probability: D-dimer may be considered, but positive results require immediate CT angiography 2, 4.
When NOT to Use D-Dimer
High probability (score 2-3): Proceed directly to CT angiography, MRI, or transesophageal echocardiography without D-dimer testing 1, 2. The negative predictive value is inadequate in this population, making D-dimer results clinically irrelevant 2.
Diagnostic Performance
D-dimer demonstrates excellent sensitivity (94-100%) for acute aortic dissection when measured within 24 hours, but specificity ranges only 40-67% 2, 5, 3. The 500 ng/mL cutoff shows 99% sensitivity for acute aortic dissection and intramural hematoma, but only 64% sensitivity for penetrating aortic ulcer 6.
Critical distinction: D-dimer performs differently across acute aortic syndrome subtypes 6:
- Acute aortic dissection: Mean 12.5 mg/L (sensitivity 99%)
- Intramural hematoma: Mean 14.8 mg/L (sensitivity 100%)
- Penetrating aortic ulcer: Mean 1.8 mg/L (sensitivity 64%)
False-Negative Scenarios
D-dimer may be falsely negative in specific high-risk situations 2:
- Thrombosed false lumen: Significantly lowers D-dimer levels
- Intramural hematoma without intimal flap: May produce negative results despite active disease
- Delayed presentation (>24 hours): D-dimer levels decline over time from symptom onset
- Short dissection length and young age: Associated with lower D-dimer values
Never rely on negative D-dimer alone in these scenarios—proceed directly to imaging. 2
Prognostic Value
Beyond diagnosis, D-dimer provides prognostic information 5, 6:
- D-dimer >5200 ng/mL independently predicts in-hospital mortality (OR 5.38) 5
- In-hospital D-dimer ≥9 mg/L independently predicts in-hospital mortality (OR 5.60) 6
- Higher levels correlate with anatomical extension and early complications 5
- Prognostic value does not extend to long-term (3-year) survival 6
Specificity Limitations
D-dimer elevation is non-specific and occurs in multiple acute conditions 2:
- Pulmonary embolism (mean 28.5 mg/mL vs. 32.9 mg/mL in dissection—cannot reliably differentiate)
- Acute myocardial infarction
- Sepsis and disseminated intravascular coagulation
- Recent thrombolytic therapy
- Malignancy, trauma, or recent surgery
D-dimer cannot distinguish between these conditions, making clinical context and imaging essential. 2
Common Pitfalls to Avoid
Never use D-dimer in high-risk patients: The test adds no value when clinical probability is high (score 2-3), and negative results do not exclude disease 1, 2
Never rely on D-dimer alone beyond 24 hours: Sensitivity declines with time from symptom onset 2, 3
Never assume negative D-dimer excludes intramural hematoma or thrombosed dissection: These conditions frequently produce false-negative results 2, 6
Never use D-dimer in hospitalized or acutely ill patients: High frequency of false-positive results renders the test unreliable in this population 2, 7
Never initiate anticoagulation based solely on elevated D-dimer: Confirmatory imaging is always required before treatment decisions 7, 4