D-dimer assay for diagnosis of deep venous thrombosis
Deep venous thrombosis (DVT) of a lower extremity is a commonly encountered clinical problem that can lead to potentially fatal outcome if pulmonary embolism develops. D-dimers, end products of fibrin clot degradation, have been used as markers for the presence of venous clots. Wells and associates reported on a randomized trial that incorporated the use of a D-dimer assay to risk-stratify the patients who require ultrasonography for assessment of possible DVT.
The investigators recruited 1,285 patients from several academic health centers who presented with symptoms suspicious for DVT, of whom 1,096 (85 percent) consented to enrollment and had no clinical exclusion criteria (e.g., resolution of initial symptoms, suspected pulmonary embolism). Participants were first screened with a clinical prediction model for the likelihood of DVT (see accompanying table on page 2006). Patients with scores of two or more were considered likely to have DVT. Participants were randomized to ultrasonography alone or D-dimer testing followed by ultrasonography if needed. All patients randomized to ultrasonography alone had an initial imaging examination that was repeated one week later if the result of the first ultrasound examination was negative but the clinical model predicted that DVT was likely. Patients randomized to the D-dimer assay–only regimen had ultrasonography if the clinical model predicted an increased risk of DVT or if the assay was positive. All trial participants were then followed for three months to determine if unsuspected DVT developed. Complete follow-up was available in 1,082 patients (99 percent).
Overall, DVT occurred in 15.7 percent of patients. Of the 566 patients randomized to the use of the D-dimer assay who had a negative assay result (and negative ultrasound result if the clinical model predicted increased risk of DVT), a venous clot was later identified during follow-up in two patients (0.4 percent). The rate of subsequently detected DVT was 1.4 percent among those initially deemed negative for clot by ultrasonography alone. Incorporation of the D-dimer assay allowed physicians to arrive at a definitive diagnosis on the initial day of presentation in 82 percent of patients compared with 65 percent of those randomized to ultrasonography alone.
The authors conclude that if their clinical prediction model deems DVT unlikely and the D-dimer assay is negative for clot, the diagnosis of DVT can be excluded safely without the need for ultrasonography.
Clinical Model for Predicting the Pretest Probability
of Deep Venous Thrombosis *
Clinical characteristic Score
Active cancer (patient receiving treatment for cancer within 1
the previous six months or currently receiving palliative
Paralysis, paresis, or recent plaster immobilization of the 1
Recently bedridden for three days or more, or major surgery 1
within the previous 12 weeks requiring general or regional
Localized tenderness along the distribution of the deep 1
Entire leg swollen 1
Calf swelling at least 3 cm larger than that on the 1
asymptomatic side (measured 10 cm below tibial tuberosity)
Pitting edema confined to the symptomatic leg 1
Collateral superficial veins (nonvaricose) 1
Previously documented deep venous thrombosis 1
Alternative diagnosis at least as likely as deep venous -2
*–A score of 2 or higher indicates that the probability of deep
venous thrombosis is likely; a score of less than 2 indicates that
the probability of deep venous thrombosis is unlikely. In patients
with symptoms in both legs, the more symptomatic leg is used.
Adapted with permission from Wells PS, Anderson DR, Rodger M, Forgie M,
Kearon C, Dreyer J, et al. Evaluation of D-dimer in the diagnosis of
suspected deep-vein thrombosis. N Engl J Med 2003;349:1228.
Wells PS, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med September 25, 2003;349:1227-35.
EDITOR’S NOTE: Of the 566 patients randomized to use of the D-dimer test, negative assay results allowed 299 patients (53 percent) to be definitively diagnosed without the need for additional ultrasonography. An accompanying editorial by Bockenstedt (1) notes with caution that a number of different D-dimer assays are available, each with various technical limits. It is not entirely clear that the high negative predictive value of the D-dimer assays employed in this research trial can be extrapolated to use in the general medical community.–B.Z.
(1.) Bockenstedt P. D-dimer in venous thromboembolism. N Engl J Med 2003;349:1203-4.
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