Evaluation of a New Rapid Quantitative D-dimer Assay in Patients with Clinically Suspected Deep Vein Thrombosis

Summary

The sensitivity and specificity for deep vein thrombosis (DVT) of a new rapid, quantitative and precise (total imprecision < 10%) D-dimer assay suitable for individual measurements (VIDAS D-DIMER, bio-Merieux, France) were evaluated in a consecutive series of 103 in- and out-patients submitted to serial compression ultrasonography (C-US) for the clinical suspicion of DVT (n = 66) or of DVT recurrence (n = 37) and symptoms lasting from 1 to 15 days. DVT was found in 22 patients at baseline testing and no patient with an initially negative C-US developed vein incompressibility at follow up. The time elapsed from the onset of symptoms was negatively associated with D-dimer levels both in patients with and in those without DVT. In the entire series of patients, the sensitivity of a positive D-dimer test (≥1.0 Μg/ml) for the presence of DVT was 96% (21/22 patients, 95% confidence interval 75-100%) with a specificity of 75% (64-84%), a negative predictive value of 98% (90-100%), a positive predictive value of 51% (35-67%), and an overall accuracy of 80% (70-87%). A normal D-dimer value (0.22 Μg/ml) was observed in one patient with DVT and symptoms lasting from 15 days. The approach of withholding C-US testing in patients with symptoms lasting from less than 11 days and D-dimer levels below the cut-off value was compared to serial C-US testing alone in a cost-effectiveness analysis subdividing the 66 patients with a first episode according to their clinical pretest probability of DVT. Thrombosis was detected in 6.7% of the patients in the low probability group (n = 15), 16.7% of the patients in the moderate probability group (n = 24), 51.9% of the patients in the high probability group (n = 27) and 8.1% of patients with suspected DVT recurrence. Calculated cost-savings for each DVT diagnosed ranged from 5% in the high pretest probability group to 55% in the low pretest probability group and to 77% in patients with suspected DVT recurrence.

The safety of avoiding C-US testing in symptomatic patients with a negative D-dimer test should be evaluated in clinical management studies.

• References

• 1 Heaton DC, Billings JD, Hickton CM. Assessment of D dimer assays for the diagnosis of deep vein thrombosis. J Lab Clin Med 1987; 110: 588-591
• 2 Rowbotham BJ, Carroll P, Whitaker AN, Bunce IH, Cobcroft RG, Elms MJ, Masci PP, Bundesen PG, Rylatt DB, Webber AJ. Measurement of crosslinked fibrin derivatives – use in the diagnosis of venous thrombosis. Thromb Haemost 1987; 57: 59-61
• 3 Ott P, Astrup L, Jensen RH, Nyeland B, Pederson B. Assessment of D-dimer in plasma: diagnostic value in suspected deep venous thrombosis of the leg. Acta Med Scand 1988; 224: 263-267
• 4 Bounameaux H, Schneider PA, Reber G, de Moerloose Ph, Krahenbuhl B. Measurement of plasma D-dimer for diagnosis of deep venous thrombosis. Am J Clin Pathol 1989; 91: 82-85
• 5 van Bergen PFMM, Knot EAR, Jonker JJC, de Boer AC, de Maat MPM. Is quantitative determination of fibrin(ogen) degradation products and throm-bin-antithrombin III complexes useful to diagnose deep venous thrombosis in outpatients. Thromb Haemost 1989; 62: 1043-1045
• 6 Chapman CS, Akhtar N, Campbell S, Miles K, O’Connor J, Mitchell VE. The use of D-Dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis. Clin Lab Haemat 1990; 12: 37-42
• 7 Elias A, Aillaud MF, Roul C, Villain Ph, Serradimigni A, Juhan-Vague I. Assessment of D-dimer measurement by ELISA or latex methods in deep vein thrombosis diagnosed by ultrasonic duplex scanning. Fibrinolysis 1990; 4: 237-240
• 8 Boneu B, Bes G, Pelzer H, Sié P, Boccalon H. D-dimers, thrombin-anti-thrombin III complexes and prothrombin fragments 1+2: diagnostic value in clinically suspected deep vein thrombosis. Thromb Haemost 1991; 65: 28-32
• 9 Chang-Liem GS, Lustermans FAT, van Wersch JWJ. Comparison of the appropriateness of the latex and ELISA D-dimer determination for the diagnosis of deep venous thrombosis. Haemostasis 1991; 21: 106-110
• 10 de Boer WA, de Haan MA, Huisman JW, Klaassen CHL. D-dimer latex assay as screening method in suspected deep venous thrombosis of the leg. A clinical study and review of the literature. Neth J Med 1991; 38: 65-69
• 11 Grau E, Linares M, Estany A, Martin F. Utility of D-dimer in the diagnosis of deep vein thrombosis in outpatients. Thromb Haemost 1991; 66: 510
• 12 Heijboer H, Ginsberg JS, Büller HR, Lensing AWA, Colly LP, ten Cate JW. The use of the D-Dimer test in combination with non-invasive testing versus serial non-invasive testing alone for the diagnosis of deep vein thrombosis. Thromb Haemost 1992; 67: 510-513
• 13 Carter CJ, Doyle DL, Dawson N, Fowler S, Devine DV. Investigations into the clinical utility of latex D-dimer in the diagnosis of deep venous thrombosis. Thromb Haemost 1993; 69: 8-11
• 14 Raimondi P, Bongard O, de Moerloose P, Reber G, Waldvogel F, Bounameaux H. D-dimer plasma concentration in various clinical conditions: implication for the use of this test in the diagnostic approach of venous thromboembolism. Thromb Res 1993; 69: 125-130
• 15 Pini M, Quintavalla R, Pattacini C, Manotti C, Poli T, Larini P, Megha A, Tagliaferri A, Dettori AG. Combined use of strain-gauge plethysmography and latex D-dimer Test in clinically suspected deep venous thrombosis. Fibrinolysis 1993; 7: 391-396
• 16 Shaukat N, Rowlands DJ, Cotter L, Walker MG, Douglas JT. The specificity and sensitivity of various ELISA methods for fibrin degradation products in the diagnosis of arterial and venous thrombosis. Thromb Haemost 1993; 69: 839
• 17 Bouman CSC, Ypma ST, Sybesma JPHB. Comparison of the efficacy of D-Dimer, fibrin degradation products and prothrombin fragment 1+2 in clinically suspected deep venous thrombosis. Thromb Res 1995; 77: 225-234
• 18 Bounameaux H, de Moerloose Ph, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994; 71: 1-6
• 19 Büller HR, Lensing AWA, Hirsh J, ten Cate JW. Deep vein thrombosis: new non-invasive diagnostic tests. Thromb Haemost 1991; 66: 133-137
• 20 Sié P. The value of laboratory tests in the diagnosis of venous thromboembolism. Haematologica 1995; 80: 57-60
• 21 Crippa L, Ravasi F, Vigano’D’Angelo S, Varagona R, Milani E, Safa O, Tessari L, D’Angelo A. Diagnostic value of compression ultrasonography and fibrinogen-related parameters for the detection of postoperative deep vein thrombosis following elective Hip replacement: a pilot study. Thromb Haemost 1995; 74: 1235-1239
• 22 Wells PS, Hirsh J, Anderson DR, Lensing AWA, Foster G, Kearon C, Weitz J, D’Ovidio R, Cogo A, Prandoni P, Girolami A, Ginsberg JS. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995; 345: 1326-1330
• 23 Lensing AWA, Prandoni P, Brandjes D, Huisman PM, Vigo M, Tomasella G, Krekt J, ten Cate JW, Huisman MV, Büller H. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989; 320: 342-345
• 24 Reber G, Minazio P, Bounameaux H, De Moerloose Ph, Durand C, Dupuy G, Pittet JL. Vidas D-dimer: a new immunoenzymatic assay for fibrin degradation products (FbDP). Fibrinolysis 1994; 8 (Suppl. 01) 126-353a
• 25 Sackett D, Haynes R, Tugwell P. In: Clinical Epidemiology a Basic Science for Clinical Medicine Little, Brown and Company; Boston: IL 1985. 1st ed 59-138
• 26 Metz CE. Basic principles of ROC analysis. Semin Nucl Med 1978; 8: 283-298
• 27 Dale S, Gogstad GO, Brosstad F, Godal HC, Holtlund J, Mørk E, Brandsnes Ø, Borch SM. Comparison of three D-Dimer assays for the diagnosis of DVT: ELISA, Latex and an immunofiltration assay (NycoCard D-Dimer). Thromb Haemost 1994; 71: 270-274
• 28 Wells PS, Brilledwards P, Stevens P, Panju A, Patel A, Douketis J, Massicotte MP, Hirsh J, Wietz JI, Kearon C, Ginsberg JS. A novel and rapid whole-blood assay for D-Dimer in patients with clinically suspected deep vein thrombosis. Circulation 1995; 91: 2184-2187
• 29 Brenner B, Pery M, Lanir N, Jabareen A, Markel A, Kaftori JK, Gaitini D, Rylatt D. Application of a bedside whole blood D-dimer assay in the diagnosis of deep vein thrombosis. Blood Coag Fibrinol 1995; 6: 219-222
• 30 The DVTENOX Study Group. Markers of hemostatic system activation in acute deep venous thrombosis. Evolution during the first days of heparin treatment. Thromb Haemost 1993 70. 909-914