Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries

Antoine Elias; Alain Cazanave; Marie Elias; Valérie Chabbert; Henri Juchet; Hélène Paradis; Philippe Carrière; Françoise Nguyen; Alain Didier; Michel Galinier; Cyrille Colin; Dominique Lauque; Francis Joffre; Hervé Rousseau

doi:10.1160/TH04-11-0734

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(05): 982-988
DOI: 10.1160/TH04-11-0734

New Technologies and Diagnostic Tools

Schattauer GmbH

Diagnostic management of pulmonary embolism using clinical assessment, plasma D-dimer assay, complete lower limb venous ultrasound and helical computed tomography of pulmonary arteries

A multicentre clinical outcome study

Antoine Elias

¹Departments of Vascular Medicine

,

Alain Cazanave

¹Departments of Vascular Medicine

,

Marie Elias

¹Departments of Vascular Medicine

,

Valérie Chabbert

²Radiology, Rangueil University Hospital Centre, Toulouse, France

,

Henri Juchet

³Emergency, Rangueil University Hospital Centre, Toulouse, France

,

Hélène Paradis

⁷Department of Cardiology and Vascular Medicine, General Hospital Centre, Auch, France

,

Philippe Carrière

⁸Department of Cardiology and Vascular Medicine, General Hospital Centre, Rodez, France

,

Françoise Nguyen

⁴Haemostasis, Rangueil University Hospital Centre, Toulouse, France

,

Alain Didier

⁵Pulmonology, Rangueil University Hospital Centre, Toulouse, France

,

Michel Galinier

⁶Cardiology, Rangueil University Hospital Centre, Toulouse, France

,

Cyrille Colin

⁹Department of Medical Information of the Hospices Civils de Lyon, Lyons, France

,

Dominique Lauque

³Emergency, Rangueil University Hospital Centre, Toulouse, France

,

Francis Joffre

²Radiology, Rangueil University Hospital Centre, Toulouse, France

,

Hervé Rousseau

²Radiology, Rangueil University Hospital Centre, Toulouse, France

› Author Affiliations

Abstract

Summary

The objective of the study was to assess the clinical validity of a non-invasive diagnostic strategy for acute pulmonary embolism using clinical assessment combined with both ELISA D-dimer and complete lower limb ultrasound (US) examination of proximal and distal veins, before single-detector helical computed tomography (CT) of pulmonary arteries. We expected the strategy to have a high diagnostic exclusion power and to safely decrease the number of CT scans. This prospective, multicenter outcome study included 274 consecutive outpatients. All underwent a priori clinical probability, D-dimer and bilateral complete lower limb US assessments. Only patients with a high clinical probability and both tests negative, or positive D-dimer and negative US assessments, underwent CT. This was deemed necessary in 114 patients (42%). At baseline, venous thromboembolism (VTE) was detected in 110 patients (40%), either by US showing proximal (n=65) or distal (n=36) thrombosis, or by CT (n=9). Anticoagulant was withheld in the remaining patients with negative results in both D-dimer and US but a non-high clinical probability (n=59), or in both US and CT (n=90), or with negative US (n=6) and inadequate CT (n=9). All patients underwent a three-month clinical follow-up. VTE occurred in one patient with inadequate CT, yielding an incidence of 0.6% [95% confidence interval: 0.1–3.4]. No patient died from VTE or had major bleeding. Using clinical probability, ELISA D-dimer and complete US before helical CT is a safe strategy resulting in a substantial reduction in CT scans.

Keywords

Pulmonary embolism - D-dimer - ultrasound / diagnosis - helical computed tomography - clinical / epidemiological studies

Full Text

References

References
1 Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPEDInvestigators. JAMA 1990; 263: 2753-9.
2 Perrier A, Desmarais S, Miron MJ. et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353: 190-5.
3 Wells PS, Anderson DR, Rodger M. et al. Excluding pulmonary embolismat the bedside without diagnostic imaging: management of patients with suspected pulmonary embolismpresenting to the emergency department byusinga simple clinical model and d-dimer. Ann Intern Med 2001; 135: 98-107.
4 Musset D, Parent F, Meyer G. et al. Diagnostic strategy for patientswith suspected pulmonary embolism: a prospective multicentre outcome study. Lancet 2002; 360: 1914-20.
5 van Strijen MJ, de Monye W, Schiereck J. et al. Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter clinical management study of 510 patients. Ann Intern Med 2003; 138: 307-14.
6 Perrier A, Roy PM, Aujesky D. et al. Diagnosing pulmonary embolism in outpatients with clinical assessment, D-dimer measurement, venous ultrasound, and helical computed tomography: a multicenter management study. Am J Med 2004; 116: 291-9.
7 Saeger W, Genzkow M. Venous thromboses and pulmonary embolisms in post-mortem series: probable causes by correlations of clinical data and basic diseases. Pathol Res Pract 1994; 190: 394-9.
8 Fernandez-Canton G, Lopez Vidaur I, Munoz F. et al. Diagnostic utility of color Doppler ultrasound in lower limb deep vein thrombosis in patients with clinical suspicion of pulmonary thromboembolism. Eur J Radiol 1994; 19: 50-5.
9 Elias A, Colombier D, Victor G. et al. Diagnostic performance of complete lower limbvenous ultrasound in patients with clinically suspected acute pulmonary embolism. Thromb Haemost 2004; 91: 187-95.
10 Hull RD, Hirsh J, Carter CJ. et al. Pulmonary angiography, ventilation lung scanning, and venography for clinically suspected pulmonary embolism with abnormal perfusion lung scan. Ann Intern Med 1983; 98: 891-9.
11 Kruit WH, de Boer AC, Sing AK. et al. The significance of venography in the management of patients with clinically suspected pulmonary embolism. J Intern Med 1991; 230: 333-9.
12 Girard P, Musset D, Parent F. et al. High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism. Chest 1999; 116: 903-8.
13 Ghaye B, Szapiro D, Willems V. et al. Combined CT venography of the lower limbs and spiral CT angiography of pulmonary arteries in acute pulmonary embolism: preliminary results of a prospective study. JBR-BTR 2000; 83: 271-8.
14 Walsh G, Redmond S. Does addition of CT pelvic venography to CT pulmonary angiography protocols contribute to the diagnosis of thromboembolic disease?. Clin Radiol 2002; 57: 462-5.
15 Begemann PG, Bonacker M, Kemper J. et al. Evaluation of the deep venous system in patients with suspected pulmonary embolismwith multi-detector CT: a prospective study in comparison to Doppler sonography. J Comput Assist Tomogr 2003; 27: 399-409.
16 Richman PB, Wood J, Kasper DM. et al. Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments. J Thromb Haemost 2003; 1: 652-7.
17 Stern JB, Abehsera M, Grenet D. et al. Detection of pelvic vein thrombosis by magnetic resonance angiography in patients with acute pulmonary embolism and normal lower limb compression ultrasonography. Chest 2002; 122: 115-21.
18 Kelly J, Hunt BJ, Moody A. Magnetic resonance direct thrombus imaging: a novel technique for imaging venous thromboemboli. Thromb Haemost 2003; 89: 773-82.
19 Giachino A. Relationship between deep-vein thrombosis in the calf and fatal pulmonary embolism. Can J Surg 1988; 31: 129-30.
20 Ohgi S, Tachibana M, Ikebuchi M. et al. Pulmonary embolisminpatientswithisolated soleal vein thrombosis. Angiology 1998; 49: 759-64.
21 Elias A, Cadene A, Elias M. et al. Extended lower limb venous ultrasound for the diagnosis of proximal and distal vein thrombosis in asymptomatic patients after total hip replacement. Eur J Vasc Endovasc Surg 2004; 27: 438-44.
22 Barrellier MT, Somon T, Speckel D. et al. Duplex ultrasonography in the diagnosis of deep vein thrombosis of the legs. Agreement between two operators. J Mal Vasc 1992; 17: 196-201.
23 Elias A, Molinier L, Bauvin E. et al. Integrating complete lower limb venous ultrasound into diagnostic strategies for pulmonary embolism: a cost-effectiveness analysis. Thromb Haemost 2004; 91: 205-7.
24 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.
25 de Moerloose P, Desmarais S, Bounameaux H. et al. Contribution of a new, rapid, individual and quantitative automated D-dimer ELISA to exclude pulmonary embolism. Thromb Haemost 1996; 75: 11-3.
26 Remy-Jardin M, Remy J, Wattinne L. et al. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique-- comparison with pulmonary angiography. Radiology 1992; 185: 381-7.
27 Remy-Jardin M, Remy J, Cauvain O. et al. Diagnosis of central pulmonary embolismwith helical CT: role of two-dimensionalmultiplanar reformations. AJR Am J Roentgenol 1995; 165: 1131-8.
28 Remy-Jardin M, Remy J, Baghaie F. et al. Clinical value of thin collimation in the diagnostic workup of pulmonary embolism. AJR Am J Roentgenol 2000; 175: 407-11.
29 Altman DG, Gardner MJ, Bryant TN. Statistics with confidence : confidence intervals and statistical guidelines. 2nd ed. London: BMJ Books; 2000
30 Kearon C, Ginsberg JS, Douketis J. et al. Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing. Ann Intern Med 2001; 135: 108-11.
31 Brown MD, Rowe BH, Reeves MJ. et al. The accuracy of the enzyme-linked immunosorbent assay D-dimer test in the diagnosis of pulmonary embolism: a meta-analysis. Ann Emerg Med 2002; 40: 133-44.
32 Leclercq MG, Lutisan JG, van Marwijk Kooy M. et al. Ruling out clinically suspected pulmonary embolismby assessment of clinical probability and D-dimer levels: a management study. Thromb Haemost 2003; 89: 97-103.
33 Schutgens RE, Ackermark P, Haas FJ. et al. Combination of a normal D-dimer concentration and a nonhigh pretest clinical probability score is a safe strategy to exclude deep venous thrombosis. Circulation 2003; 107: 593-7.
34 Perrier A, Bounameaux H, Morabia A. et al. Diagnosis of pulmonary embolism by a decision analysisbased strategy including clinical probability, D-dimer levels, and ultrasonography: amanagement study. Arch Intern Med 1996; 156: 531-6.
35 Wicki J, Perneger TV, Junod AF. et al. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001; 161: 92-7.
36 Chagnon I, Bounameaux H, Aujesky D. et al. Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism. Am J Med 2002; 113: 269-75.
37 Perrier A, Bounameaux H. Cost-effective diagnosis of deep vein thrombosis and pulmonary embolism. Thromb Haemost 2001; 86: 475-87.
38 Stein PD, Hull RD, Patel KC. et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004; 140: 589-602.
39 Pinede L, Duhaut P, Cucherat M. et al. Comparison of long versus short duration of anticoagulant therapy after a first episode of venous thromboembolism: a meta-analysis of randomized, controlled trials. J Intern Med 2000; 247: 553-62.
40 Kearon C, Ginsberg JS, Hirsh J.. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med 1998; 129: 1044-9.
41 Stein PD, Woodard PK, Hull RD. et al. Gadoliniumenhanced magnetic resonance angiography for detection of acute pulmonary embolism: an in-depth review. Chest 2003; 124: 2324-8.
42 Kavanagh EC, O'Hare A, Hargaden G. et al. Risk of pulmonary embolismafter negative MDCT pulmonary angiography findings. AJR Am J Roentgenol 2004; 182: 499-504.
43 Hartmann IJ, Prins MH, Buller HR. et al. Acute pulmonary embolism: impact of selection bias in prospective diagnostic studies.ANTELOPE Study Group.Advances in New Technologies Evaluating the Localization of Pulmonary Embolism. Thromb Haemost 2001; 85: 604-8.
44 Kruip MJ, Leclercq MG, van der Heul C. et al. Diagnostic strategies for excluding pulmonary embolism in clinical outcome studies.A systematic review. Ann Intern Med 2003; 138: 941-51.
45 Brotman DJ, Segal JB, Jani JT. et al. Limitations of D-dimer testing in unselected inpatientswith suspected venous thromboembolism. Am J Med 2003; 114: 276-82.
46 Schrecengost JE, LeGallo RD, Boyd JC. et al. Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem 2003; 49: 1483-90.