Is D-dimer (D-dimer) elevated in infections?

D-dimer Elevation in Infections

Yes, D-dimer is commonly elevated in various types of infections, reflecting the activation of both coagulation and fibrinolysis systems during inflammatory processes. 1

Mechanism of D-dimer Elevation in Infections

D-dimer is a fibrin degradation product that results from plasmin-mediated proteolysis of crosslinked fibrin. Its presence indicates both active coagulation (fibrin formation) and subsequent fibrinolysis (fibrin breakdown). In infections:

• Inflammatory cytokines trigger activation of the coagulation cascade
• Endothelial damage occurs during severe infections
• Simultaneous activation of fibrinolysis produces elevated D-dimer levels
• D-dimer has a relatively long half-life (~16 hours) in circulation 1

Types of Infections Associated with D-dimer Elevation

D-dimer elevation has been documented in various infectious conditions:

• Bacterial pneumonia: Community-acquired pneumonia (CAP) shows significant D-dimer elevation that correlates with inflammatory markers and predicts outcomes 2
• COVID-19: Markedly increased D-dimer levels are associated with disease severity and mortality 1
• Sepsis: 24% of patients with extremely elevated D-dimer (>5000 μg/L) have sepsis 3
• Meningococcal infections: N. meningitidis infections show significantly higher D-dimer levels compared to pneumococcal infections 4
• Pneumococcal infections: S. pneumoniae invasive infections show elevated D-dimer levels 4

Clinical Significance of D-dimer Elevation in Infections

The degree of D-dimer elevation correlates with:

• Disease severity: Higher levels indicate more severe infection 2, 5
• Inflammatory response: Direct correlation with inflammatory markers like WBC, CRP, and procalcitonin 2
• Prognosis: Elevated levels predict worse outcomes including ICU admission and mortality 2, 4

In N. meningitidis infections specifically:

• D-dimer <500 ng/mL: 0% mortality
• D-dimer <7,000 ng/mL: 3.5% mortality
• D-dimer >7,000 ng/mL: 26.1% mortality 4

Clinical Applications

• Prognostic value: Extremely elevated D-dimer (>5000 μg/L) is highly specific for serious illness, with 89% of such cases having VTE, sepsis, and/or cancer 3
• Monitoring: Serial D-dimer measurements may be more valuable than single measurements 6
• Treatment decisions: In COVID-19, D-dimer levels >6-fold upper limit of normal may identify patients who benefit from anticoagulation 1

Important Caveats

1. Non-standardized assays: Different D-dimer assays have variable sensitivity and specificity 1
2. Multiple interpretations: Elevated D-dimer reflects both coagulation and fibrinolysis, not just thrombosis 1
3. Other causes of elevation: Age, pregnancy, malignancy, and renal dysfunction can all elevate D-dimer independently 1, 7
4. Age adjustment: For patients >50 years, age-adjusted D-dimer cutoffs (age × 10 μg/L) improve specificity 1

Clinical Approach to Elevated D-dimer in Infections

1. Consider D-dimer elevation as a marker of disease severity in infections
2. Use D-dimer trends rather than absolute values when monitoring disease progression
3. For extremely elevated D-dimer (>5000 μg/L), maintain high suspicion for severe underlying disease including sepsis 3
4. In specific infections like COVID-19, consider D-dimer levels when assessing thrombotic risk and need for anticoagulation 1