D-Dimer Shows Promise for Pulmonary Embolism Diagnosis in Adolescents

D-dimer can serve as a sensitive test for pulmonary embolism (PE) in adolescents, and the discriminative value is higher with a cutoff of 750 ng/mL than with 500 ng/mL, according to the results of a study published in Academy of Emergency Medicine.

Pediatric PE is associated with 10% morbidity and mortality. The estimated annual incidence of PE in the pediatric population is 0.9 per 100,000 patients per year, but evidence indicates that the incidence of venous thromboembolism (VTE) is increasing in children. In hospitalized children the prevalence of PE ranges from 8.6 to 57 per 100,000 patients. Although D-dimer is commonly used in the diagnosis of PE in adults, it has not been validated in pediatric populations. To decrease the lifetime risk for malignancy, avoiding unnecessary radiation in children is desirable. However, clinicians must weigh the risk for radiation against the risk for missing a potentially fatal PE in a child.  

Nematullah Sharaf, BS, of the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University in Ohio, and colleagues conducted a case-control chart review of PE-positive patients younger than 22 who were diagnosed with PE by computed tomography (CT) or high-probability ventilation/perfusion (V/Q) scan and seen at emergency departments and hospitals within a 16-hospital system across 2 states between January 1998 and December 2016. Of the 189 PE-positive patients, 88 (46.5%) had a D-dimer test. These were then matched on a one-to-one basis by age, gender, and race to patients suspected of PE but confirmed negative by CT angiogram.

The mean D-dimer was higher in patients with massive or submassive PE (8742 ng/mL) followed by PE in central (4795 ng/mL), lobar (3758 ng/mL), and distal (2327 ng/mL) arteries. Comparison of thresholds of positive D-dimer at ≥500, ≥750, and ≥1000 ng/mL yielded a sensitivity of 90%, 82%, and 67%, respectively, and specificity of 16%, 53%, and 67%, respectively. Negative predictive values were 61%, 75%, and 71%, respectively, and positive likelihood ratios were 1.1, 1.8, and 2.2, respectively.

The researchers pointed out that the finding of a significant association between the location of a PE and the D-dimer level is novel. Using the common adult threshold of ≥500 ng/mL missed 9 patients who were PE and led to further testing in 74 patients who were deemed PE-negative. Increasing the threshold to ≥750 ng/mL increased the number of missed diagnoses to 16, and the number of false positive PE-negative patients decreased to 41. At ≥1000 ng/mL, the number of PE-positive patients missed was 24.

The sensitivity of D-dimer for PE in this adolescent population was similar to the sensitivity demonstrated in adult studies, according to the researchers. They called for prospective studies in adolescent patients with PE to confirm these results.

Reference

Sharaf N, Sharaf VB, Mace SE, Nowacki AS, Stoller JK, Carl JC. D-dimer in adolescent pulmonary embolism [published online July 16, 2018]. Acad Emerg Med. doi:10.1111/acem.13517