D-dimer assays are commonly used in clinical practice to exclude a diagnosis of deep vein thrombosis or pulmonary embolism. More recently, they have been also been used to guide patients with unprovoked venous thromboembolism (VTE) when faced with the decision to continue or stop anticoagulation after initial treatment is complete. D-dimer assays vary widely with respect to the antibody used, method of capture, instrumentation required, and calibration standard. These differences have an important influence on the operating characteristics of the assays. Consequently, the evidence available in the literature for one assay cannot simply be extrapolated to another. In this review, we will outline the general properties of D-dimer assays, discuss the concept of raising the D-dimer threshold used in diagnosis of VTE according to pretest probability and age, and provide clinical perspective on the role of D-dimer testing in the diagnosis and prognosis of VTE.

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EssentialsIt is not known if D-dimer testing alone can safely exclude pulmonary embolism (PE). We studied the safety of using a quantitative latex agglutination D-dimer to exclude PE in 808 patients. 52% of patients with suspected PE had a negative D-dimer test and were followed for 3 months. The negative predictive value of D-dimer testing alone was 99.8%, suggesting it may safely exclude PE.Summary. Background: Strategies are needed to exclude pulmonary embolism (PE) efficiently without the need for imaging tests. Although validated rules for clinical probability assessment can be combined with D-dimer testing to safely exclude PE, the rules can be complicated or partially subjective, which limits their use. Objectives: To determine if PE can be safely excluded in patients with a negative D-dimer without incorporating clinical probability assessment. Patients/Methods: We enrolled consecutive outpatients and inpatients with suspected PE from four tertiary care hospitals. All patients underwent D-dimer testing using the MDA D-dimer test, a quantitative latex agglutination assay. PE was excluded in patients with a D-dimer less than 750 lg FEU L À1 without further testing. Patients with D-dimer levels of 750 lg FEU L À1 or higher underwent standardized imaging tests for PE. All patients in whom PE was excluded had anticoagulant therapy withheld and were followed for 3 months for venous thromboembolism (VTE). Suspected events during follow-up were adjudicated centrally. Results: Eight hundred and eight patients were enrolled, of whom 99 (12%) were diagnosed with VTE at presentation. Four hundred and twenty (52%) patients had a negative D-dimer level at presentation and were not treated with anticoagulants; of these, one had VTE during follow-up. The negative predictive value of D-dimer testing for PE was 99.8% (95% confidence interval, 98.7-99.9%). Conclusions: A negative latex agglutination D-dimer assay is seen in about one-half of patients with suspected PE and reliably excludes PE as a stand-alone test.

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.