Clinical Applications of the D-Dimer Assay in Deep Venous Thrombosis
By Jessica C. Tan
Deep venous thrombosis (DVT) is a common clinical problem made significant by the attendant risk of pulmonary embolism (PE). Unfortunately, clinical diagnosis is difficult, and 95 to 90 percent of all patients examined will have either no DVT or no nonextending calf vein thrombosis and will not require anticoagulant therapy (2).
The D-dimer assay has recently come to attention as a valid noninvasive test to rule out DVT and PE. The serum assay measures cleavage products of fibrin and has been shown in many studies to have a high sensitivity and a high negative predictive value. Although not specific enough to confirm either DVT or PE, a negative D-dimer result can be accepted as sufficient evidence to rule out both disorders. The advantage over compression ultrasound with Doppler imaging is the assay’s lower cost of $45 and rapid turnaround time of less than one hour.
D-dimer fragments can be measured by a variety of assay techniques in the laboratory, including latex agglutination, enzyme-linked immunosorbent assay (ELISA), and whole blood agglutination. The classic ELISA assays provide high sensitivity and negative predictive value for DVT diagnosis, but these methods are not suitable for emergency or for individual determination (1). The latex assays, though quicker, have too low a sensitivity and negative predictive value to be recommended (1). Arrowhead Regional Medical Center (ARMC) currently employs a new and more accurate automated latex agglutination assay, Organon Teknikaa’s MDA assay, combining rapid results with high sensitivity.
In order to investigate the accuracy of the MDA D-dimer assay, Tung V. Huynh, M.D., Jessica C. Tan, and the Department of Medical Imaging at ARMC recently conducted a retrospective study of 181 patients seen between February and September 2000 at ARMC. These patients were examined by both compression ultrasound and D-dimer assay within a 36-hour time period. Of the 18 Doppler-positive patients, none displayed a negative D-dimer level (less than 500 ng/ml). Of the 163 Doppler-negative patients, 58.9 percent had negative and 41.1 percent had positive D-dimer levels. The mean D-dimer level was 2754.2 ng/ml for the Doppler-positive group (range 505-18600) and 881.9 ng/ml for the Doppler-negative group (range 35-18600). Positive D-dimer results in Doppler-negative patients were associated with myocardial infarction, stroke, CHF, infection, renal, hepatic and other inflammatory diseases. The assay demonstrated a sensitivity of 100 percent, specificity of 58.9 percent, positive predictive value of 21.2 percent, and negative predictive value of 100 percent.
In patients with clinically suspected DVT or pulmonary embolism, ARMC encourages San Bernardino County physicians to use the D-dimer assay as the first screening test. A negative D-dimer result excludes DVT and obviates further ultrasound imaging. Use of this assay in both in- and outpatient settings will result in significant savings on costs and imaging time.
Further investigation is underway. For a summary of the research or for more information, please contact Dr. Huynh at (909) 580-2236.
Jessica Tan is a third year undergraduate at Stanford University, where she is studying human biology and preparing to apply to medical school. She undertook the D-dimer research study under the direction of Tung V. Huynh, M.D. while shadowing in Arrowhead Regional Medical Center’s Medical Imaging Department. This summer Jessica also traveled in Venezuela and the Dominican Republic, working with two different medical teams to organize mobile primary-care clinics in communities at risk. Jessica’s previous research experience includes fertilization research at the University of California, Davis and immunology research at California State University, Fullerton. A President’s Scholar at Stanford, Jessica actively participates in student government, music, Christian fellowship, and Peer Health Education.
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