Comment on Clinical Presentation and Risk Stratification of Pulmonary Embolism

Dear Editor,

We read with interest Mohammed et al's excellent review regarding clinical presentation and risk stratification of pulmonary embolism (PE) that was recently published in the Journal.[1]

We have, however, concerns about the authors' strategy about the use of D-dimer testing to select which low- and intermediate-risk patients with suspected PE should proceed to imaging. Mohammed et al advocate the use of a single D-dimer cutoff level (500 ng/mL) to help make this decision. However, in recent years, it has been increasingly recognized that D-dimer cutoff levels, adjusted to such clinical factors as age and pretest clinical probability, improve the accuracy of diagnosis of PE.[2] [3] D-dimer levels increase with age and, thus, use of a rigid, fixed D-dimer cutoff level of 500 ng/mL results in a considerable decrease in specificity in older patients. Righini et al suggested adapting D-dimer cutoff levels to the patient's age to overcome this problem.[2] In the Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism trial, for patients ≤50 years, the D-dimer threshold of 500 ng/mL was used. For patients >50 years, the D-dimer cutoff level was calculated as age multiplied by 10 ng/mL. This strategy resulted in a very low rate of missed diagnoses of PE (in only 0.3% of patients). In addition, it was estimated that the use of these age-adjusted D-dimer thresholds resulted in a >20% absolute reduction in imaging studies.[2]

In the Diagnosis of Pulmonary Embolism with D-Dimer Adjusted to Clinical Probability study, an algorithm combining clinical pretest probability and varying D-dimer levels was found to be very useful.[3] A combination of low clinical pretest probability (using the Wells score[4]) and a D-dimer level less than 1,000 ng/mL accurately identified patients at low risk for PE at follow-up and these patients were excluded from chest imaging. This algorithm was associated with a remarkably low (0.05%) rate of missed diagnoses of venous thromboembolism and an absolute reduction of chest imaging of 18%.

We would urge all clinicians involved in the diagnosis and care of patients with suspected PE to be aware of the above studies.

Publication History

Article published online:
01 October 2024

• References

• 1 Mohammed AQI, Berman L, Staroselsky M. et al. Clinical presentation and risk stratification of pulmonary embolism. Int J Angiol 2024; 33 (02) 82-88
• 2 Righini M, Van Es J, Den Exter PL. et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014; 311 (11) 1117-1124
• 3 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
• 4 Wells PS, Anderson DR, Rodger M. et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer. Ann Intern Med 2001; 135 (02) 98-107