Preliminary Evaluation of two New Rapid Immunoturbidimetric D-dimer Assays in Patients with Clinically Suspected Venous Thromboembolism (VTE)

Summary

The practical utility and diagnostic accuracy of two new rapid, automated and quantitative immunoturbidimetric D-dimer methods have been evaluated in a population of 123 randomly selected patients with suspected VTE. The STA Liatest D-dimer and MDA D-dimer methods are based on the photo-optical measurement of the rate of agglutination of antibody-coated latex particles. The VIDAS D-dimer automated Elisa was used as the reference method. Diagnosis was confirmed in 51 patients (29 PE, 19 DVT, 3 DVT+PE). The immunoturbidimetric methods compared favorably with the VIDAS Elisa as judged from the correlation coefficients of linear regression lines (r = 0.82, MDA vs VIDAS; r = 0.75, STA vs VIDAS) and areas under the curve of ROC plots (VIDAS 0.83; STA 0.83; MDA 0.81). At a discriminant value of 500 ng/mL, all three D-dimer assays showed high sensitivity (96-98%), high NPV (93-97%) and moderate specificity (39-42%). Reproducibility of results around the cut-off is an important aspect of the diagnostic utility of D-dimer assays. CV's of duplicate determinations in this critical zone showed average values of 5.4% and 17.0% for MDA and STA, respectively. These data demonstrate that such rapid and automated latex-based methods for the quantitative measurement of D-dimer hold promise as reliable and cost-efficient approaches for the exclusion of VTE. Prospective patient management studies will be required to confirm this.

Key words

Ddimer - deep vein thrombosis - pulmonary embolism

• References

• 1 Bounameaux H, de Moerloose P, Perrier A, Miron MJ. D-dimer testing in suspected venous thromboembolism: an update. QJM 1997; 90: 437-42.
• 2 Cogo A, Lensing AW, Prandoni P, Hirsh J. Distribution of thrombosis in patients with symptomatic deep vein thrombosis Implications for simplifying the diagnostic process with compression ultrasound. Arch Intern Med 1993; 153: 2777-80.
• 3 Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism A statement for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation 1996; 93: 2212-45.
• 4 Lensing AW, Buller HR, Prandoni P, Batchelor D, Molenaar AH, Cogo A, Vigo M, Huisman PM, ten Cate JW. Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement. Thromb Haemost 1992; 67: 8-12.
• 5 Novelline RA, Baltarowich OH, Athanasoulis CA, Waltman AC, Greenfield AJ, McKusick KA. The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram. Radiology 1978; 126: 561-7.
• 6 Ginsberg JS, Kearon C, Douketis J, Turpie AG, Brill-Edwards P, Stevens P, Panju A, Patel A, Crowther M, Andrew M, Massicotte P, Hirsh J, Weitz JI. The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis. Arch Intern Med 1997; 157: 1077-81.
• 7 Perrier A, Desmarais S, Miron MJ, de Moerloose P, Lepage R, Slosman D, Didier D, Unger PF, Patenaude JV, Bounameaux H. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353: 190-5.
• 8 de Groot MR, van Marwijk MKooy, Pouwels JGJ, Engelage AH, Kuipers BF, Büller HR. The use of a rapid D-dimer blood test in the diagnostic work-up for pulmonary embolism: a management study. Thromb Haemost 1999; 82: 1588-92.
• 9 Janssen MC, Wollersheim H, Verbruggen B, Novakova IR. Rapid D-dimer assays to exclude deep venous thrombosis and pulmonary embolism: current status and new developments. Semin Thromb Hemost 1998; 24: 393-400.
• 10 Nieuwenhuizen W. A reference material for harmonisation of D-dimer assays Fibrinogen Subcommittee of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis. Thromb Haemost 1997; 77: 1031-3.
• 11 Farrell S, Hayes T, Shaw M. A negative SimpliRED D-dimer assay result does not exclude diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients. Ann Emerg Med 2000; 35: 121-5.
• 12 van der Graaf F, van den Borne H, van der Kolk M, de Wild PJ, Janssen GWT, van Uum SHM. Exclusion of deep venous thrombosis with D-dimer testing Comparison of 13 D-dimer methods in 99 outpatients suspected of deep venous thrombosis using venography as reference standard. Thromb Haemost 2000; 83: 191-8.
• 13 de Monyé W, Huisman MV, Pattynama MT. Observer dependency of the SimpliRed D-dimer assay in 81 consecutive patients with suspected pulmonary embolism. Thromb Res 1999; 96: 293-8.
• 14 Elms MJ, Bundesen PG, Rowbury D, Goodall S, Wakeham N, Rowell JA, Hillyard CJ, Rylatt DB. Automated determination of cross-linked fibrin derivatives in plasma. Blood Coagul Fibrinolysis 1993; 04: 159-64.
• 15 Kario K, Matsuo T, Kabayashi H, Matsuo M, Yamamoto K, Sakurai G, Baba M. Rapid quantitative evaluation of plasma D-dimer levels in thrombotic states using an automated latex photometric immunoassay. Thromb Res 1992; 66: 179-89.
• 16 Knecht MF, Heinrich F. Clinical evaluation of an immunoturbidimetric D-dimer assay in the diagnostic procedure of deep vein thrombosis and pulmonary embolism. Thromb Res 1997; 88: 413-7.
• 17 Meyer G, Fischer AM, Collignon MA, Benazzouz A, Monge F, Sors H, de Raucourt E. Diagnostic value of two rapid and individual D-dimer assays in patients with clinically suspected pulmonary embolism: comparison with microplate enzyme-linked immunosorbent assay. Blood Coagul Fibrinolysis 1998; 09: 603-8.
• 18 Reber G, Bounameaux H, Perrier A, de Moerloose P. Performances of a new, rapid and automated microlatex D-dimer assay for the exclusion of pulmonary embolism in symptomatic outpatients. Thromb Haemost 1998; 80: 719-20.
• 19 Legnani C, Pancani C, Palareti G, Guazzaloca G, Coccheri S. Contribution of a new, rapid, quantitative and automated method for D- dimer measurement to exclude deep vein thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis 1999; 10: 69-74.
• 20 Qanadli SD, Haddjam ME, Mesurolle B, Barre O, Bruckert F, Joseph F, Mignon F, Vieillard-Baron A, Dubourg O, Lacombe P. Prospective evaluation of dual-slice Helical CT in pulmonary embolism diagnosis. Correlation with selective pulmonary angiography in 157 patients. Radiology. in press
• 21 Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED) The PIOPED Investigators. JAMA 1990; 263: 2753-9.
• 22 Remy-Jardin M, Remy J, Deschildre F, Artaud D, Beregi JP, Hossein-Foucher C, Marchandise X, Duhamel A. Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy. Radiology 1996; 200: 699-706.
• 23 Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA, Vreim CE, Terrin ML, Weg JG. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992; 85: 462-8.
• 24 Lensing AW, Prandoni P, Brandjes D, Huisman PM, Vigo M, Tomasella G, Krekt J, Ten Cate JW, Huisman MV, Büller HR. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989; 320: 342-5.
• 25 Cogo A, Lensing AW, Koopman MM, Piovella F, Siragusa S, Wells PS, Villalta S, Buller HR, Turpie AG, Prandoni P. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ 1998; 316: 17-20.
• 26 Pittet JL, de Moerloose P, Reber G, Durand C, Villard C, Piga N, Rolland D, Comby S, Dupuy G. VIDAS D-dimer: fast quantitative ELISA for measuring D-dimer in plasma. Clin Chem 1996; 42: 410-5.
• 27 de Moerloose P, Desmarais S, Bounameaux H, Reber G, Perrier A, Dupuy G, Pittet JL. Contribution of a new, rapid, individual and quantitative automated Ddimer ELISA to exclude pulmonary embolism. Thromb Haemost 1996; 75: 11-3.
• 28 Legnani C, Pancani C, Palareti G, Guazzaloca G, Fortunato G, Grauso F, Golfieri R, Gianpalma E, Coccheri S. Comparison of new rapid methods for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis 1997; 08: 296-302.
• 29 Bates SM, Grand’Maison A, Johnston M, Kovacs MJ, Naguit I, Ginsberg JS. A latex D-dimer reliably excludes venous thromboembolism [Abstract]. Thromb Haemost 1999; 82 (Suppl.) 258.
• 30 Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 1993; 39: 561-77.
• 31 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44: 837-45.
• 32 Leemis LM, Trivedi KS. A comparison of approximate interval estimators for the Bernouilli parameter. The American Statistician 1996; 50: 63-8.
• 33 Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG, Bormanis J, Weitz J, Chamberlain M, Bowie D, Barnes D, Hirsh J. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998; 129: 997-1005.
• 34 de Moerloose P. D-dimer assays for the exclusion of venous thromboembolism: which test for which diagnostic strategy?. Thromb Haemost 2000; 83: 180-1.
• 35 Büller HR, Lensing AW, Hirsh J, ten Cate JW. Deep vein thrombosis: new non-invasive diagnostic tests. Thromb Haemost 1991; 66: 133-7.