Elevated D-Dimer Levels in Older Medical Emergency Department Patients: Real-Life Data on Associations with Severe Acute Medical Problems and Occult Malignancy

Background: D-dimers are frequently elevated in older Emergency Department (ED) patients and often lead to diagnostic dilemmas as specific underlying causes remain unclear. We aimed to investigate the association of elevated D-dimer levels with serious diseases with special focus on occult malignancy in the following 6 months. Methods: In this Dutch prospective cohort study in older (≥65 years) medical ED patients, D-dimer levels were routinely measured upon ED arrival but blinded to clinicians. Associations with serious medical conditions were evaluated using Cox regression, in a real-life clinical context. Results: Among 407 patients (median age 79 years), 69.8% had elevated age-adjusted D-dimers (AADD). Sepsis, ischemia, and venous thromboembolism (VTE) were all associated with AADD, although VTE was present in only 4.2% of patients. In 336 patients without active malignancy, occult malignancy was diagnosed in 9.2% within 6 months, with a time to diagnosis of 5 days. D-dimer levels ≥2000 µg/L predicted occult malignancy (HR of 2.61) and interval likelihood ratios (LRs) increased with higher D-dimer levels (highest LR 2.88). Low D-dimers (<500 µg/L) had very low LR 0.21. Conclusions: Older ED patients frequently have elevated D-dimer levels, and these levels are often associated with non-thrombotic conditions including sepsis, ischemia, and occult malignancy. While elevated levels are associated with an increased risk of occult malignancy, the absolute risk increment is modest. Consequently, routine screening for occult malignancy solely based on D-dimers is not recommended, as most malignancies were diagnosed within a short timeframe. Interestingly, occult malignancy is extremely unlikely in patients with low D-dimer levels.