Clinical Question

Can differing thresholds of d-dimer testing be used for patients with a low to moderate clinical pretest probability to rule out pulmonary embolism (PE)?

Bottom Line

The Pulmonary Embolism Graduated d-Dimer strategy increases the number of patients in the emergency department and outpatient setting who have PE ruled out via d-dimer testing, thus decreasing the need for chest imaging. The benefit is mostly seen by ruling out PE in patients with low clinical pretest probability and a d-dimer level of 500 ng per mL to 999 ng per mL. Patients with a moderate clinical pretest probability and a d-dimer level of less than 500 ng per mL can also be ruled out; however, this subset represented only 2% of the study population. (Level of Evidence = 2b)

Synopsis

Clinical pretest probability in conjunction with d-dimer testing can be a useful strategy for ruling out PE. Patients with low clinical pretest probability and a d-dimer value of less than 500 ng per mL are considered to be ruled out for PE. This study investigates whether a higher d-dimer cutoff value of less than 1,000 ng per mL in patients with low clinical pretest probability and the usual cutoff value of less than 500 ng per mL in patients with moderate clinical pretest probability can also effectively rule out PE. The investigators enrolled 2,056 patients primarily from emergency departments and outpatient clinics who had symptoms or signs suggestive of PE. The Wells Clinical Prediction Rule was applied to determine a patient's pretest probability of PE.

Using the Pulmonary Embolism Graduated d-Dimer strategy, patients with a low clinical pretest probability and a d-dimer level of less than 1,000 ng per mL or those with a moderate clinical pretest probability and d-dimer level of less than 500 ng per mL did not undergo further diagnostic testing for PE and did not receive anticoagulant therapy. All other patients underwent computed tomography pulmonary angiography or ventilation-perfusion lung scanning and received anticoagulant therapy if a PE was discovered. Patients were assessed at 90 days via telephone or a clinic visit for evidence of venous thromboembolism (VTE).

After excluding 39 enrolled patients who did not meet eligibility criteria, 2,017 patients were analyzed. Their mean age was 52 years, two-thirds were women, 86.9% had a low clinical pretest probability, 10.8% had a moderate clinical pretest probability, and 2.3% had a high clinical pretest probability. Of the 1,325 patients with a low or moderate clinical pretest probability and a negative d-dimer test result, including the subset of 315 patients with a low clinical pretest probability and a d-dimer level of 500 ng per mL to 999 ng per mL, none had VTE at 90-day follow-up. None of the 40 patients who had a moderate clinical pretest probability and d-dimer level of less than 500 ng per mL had evidence of VTE at follow-up. Increasing the d-dimer threshold to less than 1,000 ng per mL for ruling out PE in patients with a low clinical pretest probability decreased the need for chest imaging from 51.9% to 34.3%. d-dimer testing increased from 86.9% to 97.7% by testing patients with a moderate clinical pre-test probability.

Study design: Diagnostic test evaluation

Funding source: Government

Allocation: Uncertain

Setting: Emergency department

Reference: Kearon C, de Wit K, Parpia S, et al.; PEGeD Study Investigators. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med. 2019;381(22):2125–2134.