VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolismA systematic review of management outcome studiesFinancial support: Marc Carrier is a recipient of a Canadian Institute for Health Research Fellowship. Philip Wells is a recipient of a Canada Research Chair. Marc Rodger is a recipient of a Career Investigator Award from the Heart and Stroke Foundation of Canada. Grégoire Le Gal is a recipient of a University of Ottawa International Fellowship.
23 October 2008
Accepted after major revision: 23 January 2009
24 November 2017 (online)
Clinical outcome studies have shown that it is safe to withhold anticoagulant therapy in patients with suspected pulmonary embolism (PE) who have a negative D-dimer result and a low pre-test probability (PTP) either using a PTP model or clinical gestalt. It was the objective of the present study to assess the safety of the combination of a negative VIDAS© D-dimer result in combination with a non-high PTP using the Wells or Geneva models to exclude PE. A systematic literature search strategy was conducted using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Seven studies (6 prospective management studies and 1 randomised controlled trial) reporting failure rates at three months were included in the analysis. Non-high PTP was defined as “unlikely” using the Wells’ model, or “low/intermediate” PTP using either the Geneva score, the Revised Geneva Score, or clinical gestalt. Two reviewers independently extracted data onto standardised forms. A total of 5,622 patients with low/intermediate or unlikely PTP were assessed using the VIDAS D-dimer. PE was ruled out by a negative D-dimer test in 2,248 (40%, 95% confidence intervals [CI] 38.7 to 41.3%) of them. The three-month thromboembolic risk in patients left untreated on the basis of a low/intermediate or unlikely PTP and a negative D-dimer test was 3/2,166 (0.14%, 95% CI 0.05 to 0.41%). In conclusion, the combination of a negative VIDAS D-dimer result and a non-high PTP effectively and safely excludes PE in an important proportion of outpatients with suspected PE.
- 1 Laupacis Sekar N, Stiell IG. Clinical prediction rules A review and suggested modifications of methodological standards. J Am Med Assoc 1997; 277: 488-494.
- 2 Wells PS, Ginsberg JS, Anderson DR. et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998; 129: 997-1005.
- 3 Wells PS, Anderson DR, Rodger MA. et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: Increasing the models utility with the SimpliRED D-dimer. Thromb Haemost 2000; 83: 416-420.
- 4 Wicki J, Perneger TV, Junod A. et al. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001; 161: 92-97.
- 5 Le Gal G, Righini M, Roy PM. et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006; 144: 165-171.
- 6 Chagnon I, Bounameaux H, Aujesky D. et al. Comparison of two clinical prediction rules and implicit assessment for suspected pulmonary embolism. Am J Med 2002; 113: 269-275.
- 7 Klok FA, Kruisman E, Spaan J. et al. Comparison of the revised Geneva score with the Wells rule for assessing clinical probability of pulmonary embolism. J Thromb Haemost 2008; 06: 40-44.
- 8 Carrier M, Wells PS, Rodger MA. Excluding pulmonary embolism at the bedside with low pre-test probability and D-dimer: Safety and clinical utility of 4 methods to assign pre-test probability. Thromb Res 2006; 117: 469-474.
- 9 Di Nisio M, Squizzato A, Rutjes AWS. et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 05: 296-304.
- 10 Kruip MJHA, Leclercq MGL, van der Heul C. et al. Diagnostic strategies to rule out pulmonary embolism in clinical outcome studies. A systematic review. Ann Int Med 2003; 138: 941-951.
- 11 Moores LK. Diagnosis and management of pulmonary embolism: are we moving toward an outcome standard?. Arch Intern Med 2006; 166: 147-148.
- 12 Wells GA, Shea B, O’Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm
- 13 Higgins JP, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. Br Med J 2003; 327: 557-560.
- 14 Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558.
- 15 Parent F, Maitre S, Meyer G. et al. Diagnostic value of D-dimer in patients with suspected pulmonary embolism: results from a multicentre outcome study. Thromb Res 2007; 120: 195-200.
- 16 Wolf SJ, McCubbin TR, Nordenholz KE. et al. Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department. Am J Emerg Med 2008; 26: 181-185.
- 17 Elias A, Cazanave A, Elias M. et al. Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries. Thromb Haemost 2005; 93: 982-988.
- 18 Wolf SJ, McCubbin TR, Feldhaus KM. et al. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med 2004; 44: 503-510.
- 19 Fünfsinn N, Caliezi C, Demarmels Biasiutti F. et al. Rapid D-dimer testing and pre-test clinical probability in the exclusion of deep venous thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis 2001; 12: 165-170.
- 20 de Monye W, Sanson BJ, Buller HR. et al. The performance of two rapid quantitative D-dimer assays in 287 patients with clinically suspected pulmonary embolism. Thromb Res 2002; 107: 283-286.
- 21 Sijens PE, van Ingen HE, van Beek EJ. et al. Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. A comparison with pulmonary angiography. Thromb Haemost 2000; 84: 156-159.
- 22 Miron MJ, Perrier A, Bounameaux H. et al. Contribution of noninvasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients. Eur Respir J 1999; 13: 1365-1370.
- 23 Perrier A, Desmarais S, Goehring C. et al. D-dimer testing for suspected pulmonary embolism in out-patients. Am J Respir Crit Care Med 1997; 156: 492-496.
- 24 Gibson NS, Sohne M, Kruip MJ. et al. Christopher study investigators. Further validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thromb Haemost 2008; 99: 229-234.
- 25 Righini M, Nendaz M, Le Gal G. et al. Influence of age on the cost-effectiveness of diagnostic strategies for suspected pulmonary embolism. J Thromb Haemost 2007; 05: 1869-1877.
- 26 Kruip MJ, Sohne M, Nijkeuter M. et al. Christopher Study Investigators. A simple diagnostic strategy in hospitalized patients with clinically suspected pulmonary embolism. J Intern Med 2006; 260: 459-466.
- 27 Sohne M, Kruip MJ, Nijkeuter M. et al. The Chris-toper Study Group. Accuracy of clinical decision rule, D-dimer and spiral computed tomography in patients with malignancy, previous venous thromboembolism, COPD or heart failure and in older patients with suspected pulmonary embolism. J Thromb Haemost 2006; 04: 1042-1046.
- 28 Righini M, Le Gal G, De Lucia S. et al. Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism. Thromb Haemost 2006; 95: 715-719.
- 29 Sohne M, Kamphuisen PW, van Mierlo PJ. et al. Diagnostic strategy using a modified clinical decision rule and D-dimer test to rule out pulmonary embolism in elderly in- and outpatients. Thromb Haemost 2005; 94: 206-210.
- 30 Righini M, Aujesky D, Roy PM. et al. Clinical usefulness of D-dimer depending on clinical probability and cutoff value in outpatients with suspected pulmonary embolism. Arch Intern Med 2004; 164: 2483-2487.
- 31 Aujesky D, Hayoz D, Yersin B. et al. Exclusion of pulmonary embolism using C-reactive protein and D-dimer. A prospective comparison. Thromb Haemost 2003; 90: 1198-1203.
- 32 Sanchez O, Wermert D, Faisy C. et al. Clinical probability and alveolar dead space measurement for suspected pulmonary embolism in patients with an abnormal D-dimer test result. J Thromb Haemost 2006; 04: 1517-1522.
- 33 Perrier A, Howarth N, Didier D. et al. Performance of helical computed tomography in unselected out-patients with suspected pulmonary embolism. Ann Intern Med 2001; 135: 88-97.
- 34 Righini M, Le Gal G, Aujesky D. et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet 2008; 371: 1343-1352.
- 35 Goekoop RJ, Steeghs N, Niessen RW. et al. Simple and safe exclusion of pulmonary embolism in outpatients using quantitative D-dimer and Wells’ simplified decision rule. Thromb Haemost 2007; 97: 146-150.
- 36 van Belle A, Buller HR, Huisman MV. et al. Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. J Am Med Assoc 2006; 295: 172-179.
- 37 Perrier A, Roy PM, Sanchez O. et al. Multidetectorrow computed tomography in suspected pulmonary embolism. N Engl J Med 2005; 352: 1760-1768.
- 38 Steeghs N, Goekoop RJ, Niessen RW. et al. C-reactive protein and D-dimer with clinical probability score in the exclusion of pulmonary embolism. Br J Haematol 2005; 130: 614-619.
- 39 Perrier A, Roy PM, Aujesky D. et al. Diagnosing pulmonary embolism in outpatients with clinical assessement, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med 2004; 116: 291-299.
- 40 Perrier A, Desmarais S, Miron MJ. et al. Non-invasive diagnosis of venous thromboembolism in out-patients. Lancet 1999; 353: 190-195.
- 41 Kucher N, Kohler HP, Dornhofer T. et al. Accuracy of D-dimer/fibrinogen ratio to predict pulmonary embolism: a prospective diagnostic study. J Thromb Haemost 2003; 01: 708-713.
- 42 Kruip MJ, Slob MJ, Schijen JH. et al. Use of a clinical decision rule in combination with D-dimer concentration in diagnostic workup of patients with suspected pulmonary embolism: a prospective management study. Arch Intern Med 2002; 162: 1631-1635.
- 43 Schulz KF, Chalmers I, Hayes RJ. et al. Empirical evidence of bias. J Am Med Assoc 1995; 273: 408-412.
- 44 Roy PM, Colombet I, Durieux P. et al. Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism. Br Med J 2005; 331: 259.