Clinical pre-test probability adjusted versus age-adjusted D-dimer interpretation strategy for DVT diagnosis: A diagnostic individual patient data meta-analysis.

BACKGROUND: To increase the clinical usefulness of the D-dimer test in diagnosis of deep vein thrombosis (DVT), two strategies have been proposed: the age-adjusted, and the clinical pre-test probability (CPTP) adjusted interpretation. However, it is not known which of these strategies is superior. OBJECTIVE: To conduct an individual patient data (IPD) meta-analysis that compares the sensitivity, specificity, negative predictive value (NPV), and utility (the proportion of all patients who have a negative D-dimer test) when the two strategies are used to interpret D-dimer results. METHODS: Using an established IPD database, we conducted a meta-analysis to compare the two strategies. A bivariate random effects regression model was used to estimate and compare the pooled sensitivity and specificity simultaneously. The pooled NPV and utility of the two strategies was compared using a univariate random effects model. RESULTS: Four studies were eligible for this analysis, with a total of 2554 patients. Overall prevalence of DVT was 12% with substantial heterogeneity between studies (P value < .001). Both strategies have high pooled NPVs (99.8%) with a difference of 0% (95% confidence interval [CI]: -0.1, 0.1). The difference between the pooled specificity of the CPTP-adjusted strategy (57.3%) and the age-adjusted strategy (54.7%) was 2.6% (95% CI: -7.7, 12.8). The CPTP-adjusted strategy (49.4%) has a marginally greater pooled utility compared with the age-adjusted approach (47.4%), with a pooled difference of 1.9% (95% CI: -0.1, 3.9). CONCLUSIONS: Both D-dimer interpretation strategies were associated with a high and similar NPV, and similar utility.

Age-adjusted versus clinical probability-adjusted D-dimer to exclude pulmonary embolism.

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.

Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism.

Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7 %) and the age-adjusted strategy (99.6 %) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1 % vs, 50.9 %; difference 5.2 %; 95 % CI 3.5 % to 6.8 %). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.