D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review

Ann Intern Med. 2004 Apr 20;140(8):589-602. doi: 10.7326/0003-4819-140-8-200404200-00005.

Abstract

Background: Despite extensive literature, the diagnostic role of d-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple d-dimer assays and concerns about differing sensitivities and variability.

Purpose: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among d-dimer assays.

Data sources: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003.

Study selection: The researchers selected prospective studies that compared d-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies.

Data extraction: Two authors collected data on study-level factors: d-dimer assay used, cutoff value, and whether patients had suspected DVT or PE.

Data synthesis: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings.

Limitations: Although many studies evaluated multiple d-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies.

Conclusion: The ELISAs in general dominate the comparative ranking among the d-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Acute Disease
  • Enzyme-Linked Immunosorbent Assay / standards
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Hemagglutination Tests / standards
  • Humans
  • Latex Fixation Tests / standards
  • Likelihood Functions
  • Predictive Value of Tests
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / diagnosis*
  • Venous Thrombosis / blood
  • Venous Thrombosis / diagnosis*

Substances

  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D