HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Philbrick, J. T. Articles by Heim, S. Search for Related Content PubMed PubMed Citation Articles by Philbrick, J. T. Articles by Heim, S. Related Collections Evidence Based Laboratory Medicine and Test Utilization Hemostasis and Thrombosis Proteomics and Protein Markers Hematology

The D-Dimer Test for Deep Venous Thrombosis: Gold Standards and Bias in Negative Predictive Value

Departments of
¹ Internal Medicine and
² Family Practice, University of Virginia Health Sciences Center, Charlottesville, VA 22908.

^aAddress correspondence to this author at: Box 800744, University of Virginia Health Sciences Center, Charlottesville, VA 22908. Fax 434-924-1138; e-mail jtp9b{at}virginia.edu.

Background: Because venous ultrasound (US) fails to fully image the calf veins, there is the potential for US gold standard studies to classify patients with calf deep venous thrombosis (DVT) in the nondiseased category, causing bias in test index calculations. A false increase in negative predictive value (NPV) is especially likely because calf DVT false-negative tests will be counted in the numerator along with the true-negative tests in NPV calculations. We verified the presence and magnitude of this bias for the d-dimer test.

Methods: We abstracted data on overall (calf and thigh) and thigh-only test sensitivity, specificity, and NPV from the six English language studies published between March 1995 and October 2001 that compared d-dimer to a gold standard (GS) capable of imaging both thigh and calf veins and that also stratified results by thigh and calf location. Thigh specificity and NPV were calculated classifying calf DVT patients as free of disease.

Results: The six studies included 81–214 participants and provided 26 comparisons of 16 different d-dimer assays to the GS. Thigh sensitivity was higher than overall sensitivity in 22 of 26 comparisons (range, -0.3 to 8.6); thigh specificity was lower than overall specificity in all comparisons (range, -0.7 to -7.8); and thigh NPV was higher than overall NPV in 22 of 26 comparisons and unchanged in 4 comparisons (range, 0.0–9.2). NPV was >95% in 20 of the thigh results but >95% in only 8 of the overall results.

Conclusions: Different GS can produce clinically significant differences in test indices. Care must be taken in interpreting DVT studies that evaluate d-dimer as a rule-out test and that use US as a GS, because missed calf DVT can falsely increase the NPV.

The following articles in journals at HighWire Press have cited this article:

				T. L Fancher, R. H White, and R. L Kravitz Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of deep vein thrombosis: systematic review BMJ, October 9, 2004; 329(7470): 821. [Abstract] [Full Text] [PDF]

				S. A. Yablon, W. A. Rock Jr., T. G. Nick, M. Sherer, C. M. McGrath, and K. H. Goodson Deep vein thrombosis: Prevalence and risk factors in rehabilitation admissions with brain injury Neurology, August 10, 2004; 63(3): 485 - 491. [Abstract] [Full Text] [PDF]

				S. W. Heim, J. M. Schectman, M. S. Siadaty, and J. T. Philbrick D-Dimer Testing for Deep Venous Thrombosis: A Metaanalysis Clin. Chem., July 1, 2004; 50(7): 1136 - 1147. [Abstract] [Full Text] [PDF]