Short- and long-term risk stratification in acutely ill medical patients by implementing D-dimer in the emergency setting – A prospective cohort study

Objective: D-dimer testing is commonly used in emergency departments (EDs) to rule out thromboembolic events. However, elevated D-dimer levels may also be associated with an increased risk of mortality, independent of thromboembolism. Methods: This prospective observational study enrolled acutely ill medical ED patients. D-dimer measurements were conducted as part of biobanking at ED presentation. Survival at 30, 90, and 360 days was analyzed in relation to D-dimer, and Receiver operating characteristic (ROC) curves and logistic regressions were performed. Results: A total of 1035 patients were included (56% male; 61 years [IQR 46–74]). Median follow-up was 764 days (7.7% mortality). Elevated D-dimer (≥0.5 μg/mL) was observed in 46.4% of patients. Thirty-day mortality was 4.8% in patients with elevated D-dimer versus 0.2% with normal D-dimer levels (log-rank p < 0.001), while 360-day mortality was 13.5% versus 2.3% (p < 0.001), respectively. Among discharged patients, 360-day mortality was 9.2% with elevated D-dimer vs. 0.7% with normal values (log-rank p < 0.001).The ROC-derived optimal cut-off for both time points was 0.75 μg/mL (AUC 0.82 and 0.76 for 30- and 360-day mortality). Multivariable analysis adjusted for age, BMI, and comorbidities yielded elevated D-dimer to remain an independent predictor of mortality. Conclusion: In unselected ED patients, D-dimer independently predicts 30- and 360-day mortality. Beyond its diagnostic role for VTE, an elevated D-dimer—particularly in patients with no VTE and discharge from the ED—identifies individuals at increased short- and long-term risk. Incorporating D-dimer (e.g., ≥ 0.75 μg/mL) into routine risk stratification may support targeted follow-up and post-discharge management.