Physicians' Academy for Cardiovascular Education

Broader definition using clinical probability and D-dimer identifies more subjects with low PE risk

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability

Literature - Kearon C, de Wit K, Parpia S, et al. - N Engl J Med 2019;381:2125-34. DOI: 10.1056/NEJMoa1909159

Introduction and methods

Chest imaging with computed tomographic pulmonary angiography to diagnose pulmonary embolism (PE) has disadvantages, such as radiation exposure, contrast reactions, high costs, and can be time-consuming and should therefore be avoided when possible. A method to rule out PE includes assessment of clinical pretest probability (C-PTP) [1-3] and measurement of D-dimer levels. Blood D-dimer levels correlate with the probability of patients’ risk of having pulmonary embolism [4,5], and use of a threshold level of 500 ng/mL gives a high negative predictive value.

It has been established that PE can be ruled out in patients with a low C-PTP and D-dimer level<500 ng/mL [1-3,6,7], but this occurs in only 30% of outpatients. To possibly increase this number, two definitions were used to rule out PE: a D-dimer level <1000 ng/mL in patients with low C-PTP and a D-dimer <500 ng/mL in patients with a moderate C-PTP.

In the Pulmonary Embolism Graduated D-dimer (PEGeD) study, the strategy consisting of two definitions was used to rule out PE. Outpatients with symptoms or signs suggestive of PE were eligible for this prospective management study. Exclusion criteria included anticoagulant therapy for 24 hrs, major surgery within 21 days, known D-dimer level before C-PTP assessment, undergoing chest imaging, ongoing need for anticoagulant therapy. C-PTP was determined by seven item Wells prediction rule and categorized as low (Wells score 0-4.0), moderate (4.5-6.0), or high (≥6.5). D-dimer was measured in patients with a low or moderate C-PTP. The PEGeD algorithm was as follows: patients with low C-PTP and D-dimer<1000 ng/mL or with moderate C-PTP and D-dimer <500 ng/mL had no further testing for PE and did not receive anticoagulant therapy. All other patients underwent chest imaging and received anticoagulant therapy in case of PE. Study outcomes were assessed at 90 days after first diagnostic testing. Primary outcome was symptomatic venous thromboembolism (VT), including PE or deep-vein thrombosis. 2017 Patients were included from Dec 2015 and May 2018.

Main results


This prospective management study of patients with suspected PE showed that applying a strategy of low C-PTP and D-dimer<1000 ng/mL identified a group of individuals with low risk of PE. Also, the strategy of moderate C-PTP and D-dimer level <500 ng/mL to rule out PE was associated with low risk of PE. Moreover, use of the PEGeD algorithm reduced the use of chest imaging.


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