Unraveling D-Dimer Bias in PE Studies

Reference: Bannelier et al. Failure rate of D-dimer testing in patients with high clinical probability of pulmonary embolism: Ancillary analysis of three European studies. AEM Feb 2025 Date: February 27, 2025 Guest Skeptic: Dr. Lauren Westafer an Assistant Professor in the Department of Emergency Medicine at the University of Massachusetts Medical School – Baystate. She is the cofounder of FOAMcast and a pulmonary embolism and implementation science researcher. Dr. Westafer serves as the Social Media Editor and a research methodology editor for Annals of Emergency Medicine. Case: A 57-year-old woman presents to the emergency department (ED) with pleuritic posterior chest/back pain, shortness of breath, and left leg swelling. Her oxygen saturation is 95% on room air, blood pressure is 125/70, and her heart rate is 106 beats per minute. She has a swollen left leg that is tender but neurovascularly intact, without signs of cellulitis. She is on oral hormone replacement therapy (estrogen), and has a history of hypertension (on lisinopril). Chest x-ray shows no pneumonia or pneumothorax and bedside ultrasound reveals no B-lines or effusion. Background: Pulmonary embolism (PE) is a potentially life-threatening diagnosis that ED physicians must always have on their radar. The challenge, however, lies in balancing the risks of missing a PE with the harms of unnecessary imaging. D-dimer testing has changed how we workup suspected PE patients by serving as a highly sensitive yet non-specific biomarker for venous thromboembolism (VTE). This test has become a crucial component of modern PE diagnostic pathways. There is a need to “right size” testing such that we do not miss clinically important PEs without exposing very low risk patients to risks of imaging (ionizing radiation, contrast, allergic reaction, cost, and misdiagnosis). The principle behind D-dimer testing is its high negative predictive value (NPV) in ruling out PE, particularly in patients with low to moderate pretest probability. Current guidelines suggest that in these groups, a negative D-dimer result (below the defined threshold) can reliably exclude PE without the need for imaging. The Wells Score and Revised Geneva Score (RGS) and YEARS are widely used clinical prediction rules to stratify risk and guide appropriate use of D-dimer testing. However, in high-risk patients, the utility of D-dimer is less clear. The positive predictive value (PPV) of the test is low due to the presence of multiple potential causes of elevated D-dimer. Some of the causes of elevated D-dimers include cancer, infection, trauma, and post-surgical states. Given that a negative D-dimer result is uncommon in high-risk patients and the high prevalence of PE in this group, traditional teaching has recommended skipping the test and proceeding directly to CT pulmonary angiography (CTPA). The CT scanner has been called the "donut of truth" by some physicians.  Despite these long-standing recommendations, recent studies have questioned whether a D-dimer–based approach could still be safe in selected high-risk patients. With age-adjusted D-dimer thresholds and Bayesian approaches refining risk stratification, a re-evaluation of the test’s performance in high-probability patients is warranted. Clinical Question: Can an age-adjusted D-dimer strategy safely exclude PE in patients with a high clinical probability of PE? Reference: Bannelier et al. Failure rate of D-dimer testing in patients with high clinical probability of pulmonary embolism: Ancillary analysis of three European studies. AEM Feb 2025 Population: Patients with a high clinical probability of PE (Wells >6 or Revised Geneva Score >10) and underwent D-dimer testing in the ED. Excluded: Patients with missing D-dimer values, missing data elements for the RGS or Wells score, inconclusive CTPA. Intervention: Age-adjusted or standard (<500) cut off for d-dimer Comparison: None Outcome: