Age-related reduction in D-dimer cut-off specificity: Diagnostic relevance in geriatric patients

Introduction: D-dimer testing is widely used to exclude pulmonary embolism (PE), but its specificity declines sharply with age. Evidence in very old adults is limited, as most validation studies include few patients aged ≥80 years. This study aimed to identify and validate a clinically appropriate D-dimer threshold for geriatric patients. Methods: Two large cohorts of adults evaluated for suspected PE in a Geriatric Emergency Department were included. The derivation cohort included 1617 patients; the validation cohort included 2861 patients. D-dimer performance was assessed using ROC analysis, and specificity was compared across the conventional 500 μg/L FEU cut-off, the age-adjusted threshold, a fixed 1000 μg/L FEU threshold, and the optimized threshold. PE diagnosis was confirmed by CT pulmonary angiography. Results: D-dimer levels increased with age, inflammation, and renal dysfunction. In the derivation cohort, the conventional cut-off showed low specificity, particularly in patients aged ≥90 years. The age-adjusted threshold improved performance but remained insufficient in the oldest age groups. An optimized threshold of 1050 μg/L FEU provided the best balance between sensitivity (100% in the derivation cohort and 97.8% in the validation cohort) and specificity, with a negative predictive value of 99.8%. This threshold correctly reclassified 23% of patients who were false-positive at the 500 μg/L FEU cut-off. Conclusion: In very old adults, the conventional D-dimer cut-off is clinically inadequate, and the age-adjusted threshold remains suboptimal. A threshold of 1050 μg/L FEU, validated in two very old geriatric cohorts, offers a safer and more specific alternative for ruling out PE in geriatric emergency care.