Can D-dimer Be Elevated with Infection?
Yes, D-dimer is frequently elevated in infections including sepsis, pneumonia, and other infectious states, and this elevation is clinically significant for risk stratification and prognosis. 1
Infection as a Cause of D-dimer Elevation
D-dimer elevates in infection through multiple mechanisms related to the inflammatory and coagulation cascade activation that occurs during severe infectious processes:
Sepsis is one of the most common causes of markedly elevated D-dimer levels, with the International Society on Thrombosis and Haemostasis recognizing that coagulopathy development in sepsis from various infectious agents is a key feature associated with poor outcomes 1
Pneumonia specifically causes D-dimer elevation, with research demonstrating that elevated plasma D-dimer in adult community-acquired pneumonia patients correlates with increased inflammatory markers (WBC, hs-CRP, PCT) and predicts ICU admission and 30-day mortality 2
The American College of Cardiology explicitly states that treatment of bacterial superinfections is important when managing elevated D-dimer and coagulopathy, acknowledging infection as a direct cause 1
Clinical Significance in COVID-19 Infection
The COVID-19 pandemic provided extensive evidence of infection-related D-dimer elevation:
D-dimer ≥0.5 mg/L was noted in 46.4% of COVID-19 patients tested, with 60% of patients with severe illness demonstrating this elevation 1
Markedly elevated D-dimer (three- to fourfold increase) in COVID-19 patients warrants hospital admission even without other severe symptoms, as this signifies increased thrombin generation 1
D-dimer >2.12 μg/mL in COVID-19 patients was associated with mortality, compared to 0.61 μg/mL in survivors 1
Magnitude of Elevation Matters
The degree of D-dimer elevation in infection has prognostic implications:
Ultra-high D-dimer levels (>5000 ng/mL) occur in multiple conditions including sepsis, pneumonia, and other infections, with one study showing sepsis in 24% and pneumonia in a significant proportion of patients with these extreme elevations 3, 4
D-dimer >6 times the upper limit of normal is a consistent predictor of thrombotic events and poor overall prognosis in infected patients 1
When D-dimer levels are >15,000 ng/mL without a clear diagnosis, mortality reaches 75%, indicating severe underlying disease often including infection 3
Critical Clinical Pitfall
The major pitfall is assuming elevated D-dimer always indicates thromboembolism and missing the underlying infection:
D-dimer can be elevated in infection, cancer, recent surgery/trauma, pregnancy, advanced age, liver disease, and inflammatory states 5
Even very high D-dimer levels (>5000 ng/mL) in symptomatic patients may not indicate pulmonary embolism, as demonstrated in a case of COPD exacerbation with D-dimer of 5.58 μg/mL where CT angiography ruled out PE 6
89% of patients with extremely elevated D-dimer (>5000 μg/L) had VTE, sepsis, and/or cancer, meaning infection accounts for a substantial proportion alongside thrombosis 4
Practical Management Algorithm
When encountering elevated D-dimer in a patient with suspected or confirmed infection:
Risk stratify based on magnitude: D-dimer 3-4 times normal warrants admission; >6 times normal predicts poor prognosis 1
Monitor coagulation parameters: Check PT, platelet count, and fibrinogen to identify evolving coagulopathy or DIC 1
Don't rule out thrombosis solely based on infection presence: The International Society on Thrombosis and Haemostasis recommends obtaining D-dimer, PTT, platelet count, and fibrinogen for risk stratification in infected patients, as both infection and thrombosis may coexist 1
Initiate prophylactic anticoagulation in hospitalized patients with markedly elevated D-dimer unless contraindicated (active bleeding or platelets <25 × 10⁹/L) 7
Treat the underlying infection aggressively, as the American College of Cardiology emphasizes that treatment of bacterial superinfections is important when managing coagulopathy 1