D-Dimer Testing for Deep Venous Thrombosis: A Metaanalysis

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 50; no. 7; pp. 1136 - 1147
• Main Authors: Heim, Steven W, Schectman, Joel M, Siadaty, Mir S, Philbrick, John T
• Format: Journal Article
• Language: English
• Published: Washington, DC Am Assoc Clin Chem 01.07.2004; American Association for Clinical Chemistry; Oxford University Press
• Subjects: Analytical, structural and metabolic biochemistry; Bibliographic literature; Biological and medical sciences; Biomarkers - blood; Diagnostic tests; Emergency medical care; Fibrin Fibrinogen Degradation Products - analysis; Fibrin Fibrinogen Degradation Products - standards; Fundamental and applied biological sciences. Psychology; Humans; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Molecular biophysics; Patients; Predictive Value of Tests; Quality standards; Reference Standards; Sensitivity and Specificity; Systematic review; Thrombosis; Ultrasonic imaging; Venous Thrombosis - blood; Venous Thrombosis - diagnosis; Vascular disease; Clinical biology; Deep vein thrombosis; Cardiovascular disease; Biochemistry; Molecular biology; D dimer; Medical screening; Venous disease; Metaanalysis
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2004.031765

The use of D-dimer assays as a rule-out test for deep venous thrombosis (DVT) is controversial. To clarify this issue we performed a systematic review of the relevant literature. We identified eligible studies, using MEDLINE entries from February 1995 through October 2003, supplemented by a review of bibliographies of relevant articles. Studies reporting accuracy evaluations comparing D-dimer test results with lower extremity ultrasound or venography in symptomatic patients with suspected acute DVT were selected for review. Two reviewers critically appraised each study independently according to previously established methodologic standards for diagnostic test research. Those studies judged to be of highest quality were designated Level 1. The 23 Level 1 studies reported data on 21 different D-dimer assays. There was wide variation in assay sensitivity, specificity, and negative predictive values, and major differences in methodology of reviewed studies. A multivariate analysis of assay performance, controlling for sample size, DVT prevalence, reference standard, and patient mix, found few differences among the assays in effect on test performance as measured by diagnostic odds ratio. Increasing prevalence of DVT was associated with poorer test performance (P = 0.01), whereas the choice of venography as the reference standard was associated with better test performance (P <0.005). Explanations for the wide variation in assay performance include differences in biochemical and technical characteristics of the assays, heterogeneity and small size of patient groups, and bias introduced by choice of reference standards. Assay sensitivity and negative predictive value were frequently <90%, uncharacteristic of a good rule-out test. General use of D-dimer assays as a stand-alone test for the diagnosis of DVT is not supported by the literature.