D-dimer for the diagnosis of recurrent DVT

Diagnosing recurrent venous thromboembolic disease of the legs is more difficult than diagnosing a first episode of DVT. Patients who have had an initial DVT are often left with some degree of post-phlebitic syndrome, which can mimic the symptoms of recurrent disease. Duplex ultrasound often remains abnormal after a DVT, making the distinction between recurrent disease and old disease problematic.

D-dimer measurement, which is elevated with thromboembolic events, is quite sensitive for the detection of initial DVT. Although not very specific, its sensitivity is such that a negative D-dimer has good negative predictive value. Since imaging studies are problematic for diagnosing recurrent disease, the D-dimer assay should be quite useful in helping to rule out recurrent DVT. This study from Oklahoma, published in the December 7 Annals of Internal Medicine, investigated the utility of a negative D-dimer assay in excluding recurrent venous thromboembolism.

Three hundred consecutive patients with suspected recurrent DVT had D-dimer levels assessed. Those with negative results (<48 mcg/ml) did not undergo any further diagnostic testing. Those with positive results underwent compression ultrasound imaging. For three months after initial presentation, patients were followed up with imaging studies if there were any symptoms of recurrent DVT or PE, and also clinically at three months.

Of the 300 patients, 166 had positive D-dimer studies; one half of these had negative ultrasound studies, one third had positive studies and the remainder were inconclusive.

Of the 300 patients, 134 (45%) had negative D-dimer studies and did not undergo duplex scanning. In this D-dimer negative group, 11 patients returned for symptoms of recurrent thromboembolism. Of these, there were two cases of documented thromboembolism (one DVT and one PE); 4 patients had negative diagnostic tests and 5 had inconclusive studies. There was one death in the D-dimer negative group, a sudden death, which may have been a myocardial infarction. Thus, the rate of documented recurrent thromoembolism was 2/134 (1.5%). Including the sudden death and the 5 inconclusive studies, the recurrence rate was 8/134 (6%).

As the authors state:

The acceptable upper limit for the incidence of venous thromboembolism on follow-up in patients with a negative D-dimer test result remains a clinical judgment in the individual patient. The prognosis on follow-up in our patients with negative D-dimer test results is similar to the prognosis of patients with negative results on combined impedance plethysmography and fibrinogen leg scanning; it is also similar to the prognosis of patients with negative venography results.

These results, though not conclusive, are certainly useful. D-dimer testing is of utility in excluding a first episode of DVT; it is likely to be much more useful in excluding recurrent DVT, since imaging studies and symptoms are more difficult to interpret in this setting.

One aspect of this article that struck me was how often the authors mentioned the specific name of the D-dimer assay used here. It was named not only in the methods, where it is appropriate, but also in the discussion and even twice in the abstract! In the background paragraph, the authors state that the sensitivity of the [assay] … has been reported to be 96% to 100% in patients with suspected first-episode DVT or symptomatic pulmonary embolism”. And they quote two references. In fact, one of these references is a comparison of 13 assays in the diagnosis of DVT. The method used by the authors here is not among the two that were found to be most sensitive!

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