Use of D-dimer to Screen for Cerebral Pathology in ED Patients with Non-traumatic Headache and Normal Neurological Exam

Introduction: Our goal in this study was to evaluate the diagnostic utility of bedside D-dimer testing for identifying secondary headache due to intracranial pathology among patients presenting to the emergency department (ED) with non-traumatic headache and no neurological deficits. Methods: We conducted this prospective, multicenter, cross-sectional study across six tertiary care EDs in Türkiye. Adult patients presenting with non-traumatic headache and no neurological deficits who underwent cranial computed tomography (CT) based on clinical suspicion for intracranial pathology were enrolled. Exclusion criteria were recent trauma, pregnancy, fever, hematologic conditions, and known intracranial pathology. We measured bedside D-dimer using a D-dimer assay with a predefined threshold of 500 nanograms per milliliter. The primary outcome was secondary headache related to intracranial pathologies as determined on the index CT and additional tests as needed or during one-month follow-up. Results: Of the 3,279 patients screened, 1,522 were included in the final analysis. Secondary headache due to intracranial pathology was identified in 57 patients (3.7%). The most common etiologies were subarachnoid hemorrhage (n = 20, 35.1%), ischemic stroke (n = 16, 28.1%), cerebral vein thrombosis (n = 6, 10.5%), and subdural hemorrhage (n=6, 10.5%). Bedside D-dimer demonstrated a sensitivity of 82.5% (95% CI, 70-91%) and specificity of 89.2% (95% CI, 87-91%) for identifying intracranial pathology, with a positive likelihood ratio of 7.6 (95% CI, 6.3-9.2) and negative likelihood ratio of 0.2 (95% CI, 0.1-0.35). Diagnostic accuracy was highest for cerebral venous thrombosis: sensitivity was 100% with a wide CI (95% CI, 54-100%), specificity was 86.8% (95% CI, 85-88%), and positive likelihood ratio was 7.6 (95% CI, 6.7-8.6). For subarachnoid hemorrhage, where sensitivity reached 90% (95% CI, 68-99%), specificity was 87.5% (95% CI, 86-89%), the positive likelihood ratio was 7.2 (95% CI: 5.9–8.8), and the negative likelihood ratio was 0.1 (95% CI: 0.03-0.4). Conclusion: Bedside D-dimer testing showed moderate performance as a screening adjunct in ruling out secondary headache due to intracranial causes in ED patients with non-traumatic headache and no neurological findings.