Age-adjusted versus clinical probability-adjusted D-dimer to exclude pulmonary embolism. Issue 167 (July 2018) - Takach Lapner, Sarah
Abstract: Introduction: A low D-dimer can exclude suspected pulmonary embolism (PE) in cases with low or intermediate clinical probability of disease. Yet D-dimer is nonspecific, so many cases without PE require imaging. D-dimer's specificity is improved by increasing the threshold for a positive test with age (age × 10 ng/mL; age-adjusted D-dimer; AADD) or clinical probability of PE (1000 ng/mL if low and 500 ng/mL if intermediate clinical probability; clinical probability-adjusted D-dimer; CPADD). It is unclear which approach is preferable. Objectives: We report the sensitivity, specificity and negative predictive value (NPV) of AADD compared to CPADD in suspected PE. Materials and methods: A retrospective cohort of 3500 consecutive cases imaged for suspected PE at two U.S. emergency departments was assembled. We analyzed cases with low or intermediate clinical probability of PE (Revised Geneva Score) who had a D-dimer. The outcome was acute PE on imaging at presentation. Results: Of the 3500 cases, 1745 were eligible. 37% were low, and 63% were intermediate clinical probability of PE. PE was present in 145 (8.3%) cases. Sensitivity of CPADD was 87.5% vs. 96.6% for AADD (difference 9.1%; 95% CI 4.3% to 14.0%). NPV of CPADD was 97.1% vs. 99.0% for AADD (difference 1.9%; 95% CI, 0.7% to 3.1%). Specificity of CPADD was 37.5% vs. 30.2% for AADD (difference –7.3%; 95% CI –9.4% to –5.1%). D-dimer was negative in 35.4% of cases using CPADD vs. 28.0% using AADD. Conclusions: CPADD modestly improved the specificity of D-dimer, but had a lower NPV than AADD. AADD appears preferable in this analysis. Highlights: D-dimer is a sensitive test to rule out pulmonary embolism, but is non-specific. A higher D-dimer threshold in low probability patients improves specificity. A higher D-dimer threshold in elderly patients also improves specificity. More pulmonary embolism ruled out if threshold increased with probability versus age. More pulmonary embolism missed if threshold increased with probability versus age.