Cost-effective Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism

Summary

Suspected acute venous thromboembolism is a frequent and challenging clinical problem. Phlebography and pulmonary angiography are costly and invasive and, hence, ill-suited for diagnosing a disease present in only 20% of patients in whom it is suspected. Novel noninvasive instruments, such as plasma D-dimer measurement, lower limb compression ultrasonography and helical CT scan are important breakthroughs in the management of patients with suspected venous thromboembolism. However, none of these instruments is ideal, and they must be combined in rational and cost-effective diagnostic algorithms including clinical assessment, which is increasingly standardized. Such strategies must be validated in management studies, in which patients without venous thromboembolism are not treated and followed up during 3 months. Suspected massive pulmonary embolism is a distinct clinical situation requiring a specific diagnostic approach, in which echocardiography plays a major role. This paper reviews the performance of clinical evaluation and diagnostic tests for venous thromboembolism, and recently validated diagnostic schemes.

Key words

Pulmonary embolism - deep vein thrombosis - diagnosis - cost-effectiveness analysis - outcome studies

• References

• 1 Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000; 83: 657-60.
• 2 Anderson Jr FA, Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B. et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. Arch Intern Med 1991; 151: 933-8.
• 3 The PIOPED. Investigators. Value of the ventilation-perfusion scan in cute pulmonary embolism. JAMA 1990; 263: 2753-9.
• 4 Wells PS, Anderson DR, Bormani J, Guy F, Mitchell M, Gray L. et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997; 350: 1795-8.
• 5 Wells PS, Ginsberg JS, Anderson DR, Kearon C, Gent M, Turpie AG. et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med 1998; 129: 997-1005.
• 6 Moser KM. Venous thromboembolism. Am Rev Respir Dis 1990; 141: 235-49.
• 7 Sevitt S, Gallagher NG. Venous thrombosis and pulmonary embolism: clinicopathologic study in injured and burned patients. Br J Surg 1961; 48: 475-82.
• 8 Hull RD, Hirsh J, Carter CJ, Jay RM, Dodd PE, Ockelford PA. 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.
• 9 Meignan M, Rosso J, Gauthier H, Brunengo F, Claudel S, Sagnard L. et al. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med 2000; 160: 159-64.
• 10 Moser KM, Fedullo PF, LitteJohn JK, Crawford R. Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis. JAMA 1994; 271: 223-5.
• 11 Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M. 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: 416-20.
• 12 Perrier A, Desmarais S, Miron MJ, de Moerloose P, Lepage R, Slosman D. et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353: 190-5.
• 13 Bounameaux H, de Moerloose P, Perrier A, Miron MJ. D-dimer testing in suspected venous thromboembolism: an update. QJM 1997; 90: 437-42.
• 14 Becker DM, Philbrick JT, Bachhuber TL, Humphries JE. D-dimer testing and acute venous thromboembolism. A shortcut to accurate diagnosis? Arch Intern Med 1996; 156: 939-46.
• 15 Janssen MC, Wollersheim H, Verbruggen B, Novakova IR. Rapid Ddimer assays to exclude deep venous thrombosis and pulmonary embolism: current status and new developments. Semin Thromb Hemost 1998; 24: 393-400.
• 16 Becker DM, Philbrick JT, Abbitt PL. Real-time ultrasonography for the diagnosis of lower extremity deep venous thrombosis. The wave of the future? Arch Intern Med 1989; 149: 1731-4.
• 17 Lensing AWA, Prandoni P, Brandjes D, Huisman PM, Vigo M, Tomasella G. et al. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989; 320: 342-5.
• 18 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.
• 19 Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med 2000; 132: 227-32.
• 20 Mullins MD, Becker DM, Hagspiel KD, Philbrick JT. The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism. Arch Intern Med 2000; 160: 293-8.
• 21 Sanson BJ, Meinders AJ, Kraaijenhagen RA, van Beek EJ, Buller HR. Requirements for appropriate evaluation of diagnostic tests in suspected pulmonary embolism. Haematologica 1999; 84: 78-81.
• 22 Hyers TM, Agnelli G, Hull RD, Weg JG, Morris TA, Samama M. et al. Antithrombotic therapy for venous thromboembolic disease. Chest 1998; 114: 561S-78.
• 23 Zidane M, Schram MT, Planken EW, Molendijk WH, Rosendaal FR, van der Meer FJ. et al. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. Arch Intern Med 2000; 160: 2369-73.
• 24 Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18: 3078-83.
• 25 Hull RD, Raskob GE, Ginsberg JS, Panju AA, Brill-Edwards P, Coates G. et al. A noninvasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med 1994; 154: 289-97.
• 26 Perrier A, Buswell L, Bounameaux H, Didier D, Morabia A, de Moerloose P. et al. Cost-effectiveness of noninvasive diagnostic aids in suspected pulmonary embolism. Arch Intern Med 1997; 157: 2309-16.
• 27 Perone N, Bounameaux H, Perrier A. Comparison of four strategies for diagnosing deep vein thrombosis: a cost-effectiveness analysis. Am J Med 2001; 110: 33-40.
• 28 Perrier A, Sarasin FP, Howarth N, Bounameaux H. Diagnostic strategies for suspected pulmonary embolism including helical computed tomography: a cost-effectiveness analysis. Arch Int Med. 2001 submitted.
• 29 Michel BC, Seerden RJ, Rutten FF, Van Beek EJ, Buller HR. The cost-effectiveness of diagnostic strategies in patients with suspected pulmonary embolism. Health Econ 1996; 5: 307-18.
• 30 Hull RD, Feldstein W, Stein PD, Pineo GF. Cost-effectiveness of pulmonary embolism diagnosis. Arch Intern Med 1996; 156: 68-72.
• 31 Haeger K. Problems of acute deep venous thrombosis. I. The interpretation of signs and symptoms. Angiology 1969; 20: 219-23.
• 32 Barnes RW, Wu KK, Hoak JC. Fallibility of the clinical diagnosis of venous thrombosis. JAMA 1975; 234: 605-7.
• 33 Miron MJ, Perrier A, Bounameaux H. Clinical assessment of suspected deep vein thrombosis: comparison between a score and empirical assessment. J Intern Med 2000; 247: 249-54.
• 34 Bigaroni A, Perrier A, Bounameaux H. Is clinical probability assessment of deep vein thrombosis by a score really standardized?. Thromb Haemost 2000; 83: 788-9.
• 35 Stein PD, Henry JW. Clinical characteristics of patients with acute pulmonary embolism stratified according to their presenting syndromes. Chest 1997; 112: 974-9.
• 36 Stein PD, Terrin ML, Hales CA, Palevsky HI, Saltzman HA, Thompson T. et al. Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease. Chest 1991; 100: 598-603.
• 37 Stein PD, Willis PWd, De Mets DL. History and physical examination in acute pulmonary embolism in patients without preexisting cardiac or pulmonary disease. Am J Cardiol 1981; 47: 218-23.
• 38 Poulose KP, Reba RC, Gilday DL, Deland FH, Wagner HN. Diagnosis of pulmonary embolism. A correlative study of the clinical, scan, and angiographic findings. BMJ 1970; 3: 67-71.
• 39 Elliott CG, Goldhaber SZ, Visani L, DeRosa M. Chest radiographs in acute pulmonary embolism. Results from the International Cooperative Pulmonary Embolism Registry. Chest 2000; 118: 33-8.
• 40 Stein PD, Goldhaber SZ, Henry JW. Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest 1995; 107: 139-43.
• 41 Rodger MA, Carrier M, Jones GN, Rasuli P, Raymond F, Djunaedi H. et al. Diagnostic value of arterial blood gas measurement in suspected pulmonary embolism. Am J Respir Crit Care Med 2000; 162: 2105-8.
• 42 Rodger M, Makropoulos D, Turek M, Quevillon J, Raymond F, Rasuli P. et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol 2000; 86: 807-9.
• 43 Perrier A, Miron MJ, Desmarais S, de Moerloose P, Slosman D, Didier D. et al. Using clinical evaluation and lung scan to rule out suspected pulmonary embolism: Is it a valid option in patients with normal results of lower-limb venous compression ultrasonography?. Arch Intern Med 2000; 160: 512-6.
• 44 Wicki J, Perneger TV, Junod A, Bounameaux H, Perrier A. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001; 161: 92-7.
• 45 Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 1994; 71: 1-6.
• 46 D’Angelo A, D’Alessandro G, Tomasini L, Pittet JL, Dupuy G, Crippa L. Evaluation of a new rapid quantitative D-dimer assay in patients with clinically suspected deep vein thrombosis. Thromb Haemost 1996; 75: 412-6.
• 47 Borg JY, Lévesque H, Cailleux N, Franc C, Hellot MF, Courtois H. Rapid quantitative D-dimer assay and clinical evaluation for the diagnosis of clinicall suspected deep vein thrombosis. Thromb Haemost 1997; 77: 602-3.
• 48 Janssen MCH, Heebels AE, de Metz M, Verbruggen H, Wollersheim H, Janssen S. et al. Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of deep venous thrombosis. Thromb Haemost 1997; 77: 262-6.
• 49 Wells PS, Brill-Edwards P, Stevens P, Panju A, Patel A, Douketis J. et al. A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis. Circulation 1995; 91: 2184-7.
• 50 Turkstra F, van Beek JR, ten Cate JW, Büller HR. Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients. Thromb Haemost 1996; 76: 9-11.
• 51 Brenner B, Pery M, Lanir N, Jabareen A, Markel A, Kaftori JK. et al. Application of a bedside whole bloood D-dimer assay in the diagnosis of deep vein thrombosis. Blood Coag Fibrinolysis 1995; 6: 219-22.
• 52 Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Lewandowski B. SimpliRED D-dimer can reduce the diagnostic tests in suspected deep vein thrombosis. Lancet 1998; 351: 1405-6.
• 53 Perrier A, Desmarais S, Goehring C, de Moerloose P, Morabia A, Unger PF. et al. D-dimer testing for suspected pulmonary embolism in outpatients. Am J Respir Crit Care Med 1997; 156: 492-6.
• 54 de Moerloose P, Desmarais S, Bounameaux H, Reber G, Perrier A, Dupuy G. et al. Contribution of a new, rapid, individual and quantitative automated D-dimer ELISA to exclude pulmonary embolism. Thromb Haemost 1996; 75: 11-3.
• 55 Ginsberg JS, Wells PS, Brill-Edwards Pe. Application of a novel and rapid whole blood assay for D-Dimer in patients with clinically suspected pulmonary embolism. Thromb Haemost 1995; 73: 379-86.
• 56 Ginsberg JS, Wells PS, Kearon C, Anderson D, Crowther M, Weitz JI. et al. Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Intern Med 1998; 129: 1006-11.
• 57 Oger E, Leroyer C, Bressollette L, Nonent M, Le Moigne E, Bizais Y. et al. Evaluation of a new, rapid, and quantitative D-Dimer test in patients with suspected pulmonary embolism. Am J Respir Crit Care Med 1998; 158: 65-70.
• 58 Righini M, Goehring C, Bounameaux H, Perrier A. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 2000; 109: 357-61.
• 59 Le Blanche AF, Siguret V, Settegrana C, Bohus S, Le Masne de Chermont E, Andreux JP. et al. Ruling out acute deep vein thrombosis by ELISA plasma D-dimer assay versus ultrasound in inpatients more than 70 years old. Angiology 1999; 50: 873-82.
• 60 Miron MJ, Perrier A, Bounameaux H, de Moerloose P, Slosman DO, Didier D. et al. Contribution of noninvasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients. Eur Respir J 1999; 13: 1365-70.
• 61 Wells PS, Anderson DR. Diagnosis of deep-vein thrombosis in the year 2000. Curr Opin Pulm Med 2000; 6: 309-13.
• 62 Anderson DR, Lensing AWA, Wells PS, Levine MN, Weitz JR, Hirsh J. Limitations of impedance plethysmography in the diagnosis of clinically suspected deep-vein thrombosis. Ann Intern Med 1993; 118: 25-30.
• 63 Ginsberg JS, Wells PS, Hirsh J, Panju AA, Patel MA, Malone DE. et al. Reevaluation of the sensitivity of impedance plethysmography for the detection of proximal deep vein thrombosis. Arch Intern Med 1994; 154: 1930-3.
• 64 Heijboer H, Büller HR, Lensing AWA, Turpie AGG, Colly LP, ten Cate JW. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med 1993; 329: 1365-9.
• 65 Lensing AW, Doris CI, McGrath FP, Cogo A, Sabine MJ, Ginsberg J. et al. A comparison of compression ultrasound with color Doppler ultrasound for the diagnosis of symptomless postoperative deep vein thrombosis. Arch Intern Med 1997; 157: 765-8.
• 66 Cogo A, Lensing AWA, 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.
• 67 Cogo A, Lensing AWA, Koopman MMW, Piovella F, Siragusa S, Wells PS. et al. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ 1998; 316: 17-20.
• 68 Bernardi E, Prandoni P, Lensing AW, Agnelli G, Guazzaloca G, Scannapieco G. et al. D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. The Multicentre Italian D-dimer Ultrasound Study Investigators Group. BMJ 1998; 317: 1037-40.
• 69 Kakkar VV, Flanc C, Howe CT, Clarke MB. Natural history of postoperative deep-vein thrombosis. Lancet 1969; 2: 230-2.
• 70 Birdwell BG, Raskob GE, Whitsett TL, Durica SS, Comp PC, George JN. et al. The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis. Ann Intern Med 1998; 128: 1-7.
• 71 Killewich LA, Nunnelee JD, Auer AI. Value of lower extremity venous duplex examination in the diagnosis of pulmonary embolism. J Vasc Surg 1993; 17: 934-8.
• 72 Smith LL, Conrad I, Sirr S. Pulmonary embolism: confirmation with venous duplex US as adjunct to lung scanning. Radiology 1994; 191: 143-7.
• 73 Turkstra F, Kuijer PMM, van Beek EJR, Brandjes DPM, ten Cate JW, Büller HR. Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med 1997; 126: 775-81.
• 74 Perrier A, Bounameaux H, Morabia A, de Moerloose P, Slosman D, Didier D. et al. Diagnosis of pulmonary embolism by a decision analysis-based strategy including clinical probability, D-dimer levels, and ultrasonography: a management study. Arch Intern Med 1996; 156: 531-6.
• 75 Wells PS, Lensing AWA, Davidson BL, Prins MH, Hirsh J. Accuracy of ultrasound for the diagnosis of deep venous thrombosis in asymptomatic patients after orthopedic surgery. Ann Intern Med 1995; 122: 47-53.
• 76 Perrier A, Bounameaux H. Ultrasonography of leg veins in patients suspected of having pulmonary embolism. Ann Intern Med 1998; 128: 243.
• 77 Wells PS, Hirsh J, Anderson DR, Lensing AW, Foster G, Kearon C. et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995; 345: 1326-30.
• 78 Alderson PO, Martin EC. Pulmonary embolism: diagnosis with multiple imaging modalities. Radiology 1987; 164: 297-312.
• 79 Gottschalk A, Sostman HD, Coleman RE, Juni JE, Thrall J, McKusick KA. et al. Ventilation-perfusion scintigraphy in the PIOPED study. Part II Evaluation of scintigraphic criteria and interpretations. J Nucl Med 1993; 34: 1119-26.
• 80 Sostman HD, Coleman RE, De Long DM, Newman GE, Paine S. Evaluation of revised criteria for ventilation-perfusion scintigraphy in patients with suspected pulmonary embolism. Radiology 1994; 193: 103-7.
• 81 Hull RD, Raskob GE, Coates G, Panju AA. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism. Chest 1990; 97: 23-6.
• 82 Kipper MS, Moser KM, Kortman KE, Ashburn WL. Longterm follow-up of patients with suspected pulmonary embolism and a normal lung scan. Chest 1982; 82: 411-5.
• 83 de Groot MR, Turkstra F, van Marwijk Kooy M, Oostdijk AH, van Beek EJ, Buller HR. Value of chest X-ray combined with perfusion scan versus ventilation/perfusion scan in acute pulmonary embolism. Thromb Haemost 2000; 83: 412-5.
• 84 Rémy-Jardin M, Rémy J, Wattinne L, Giraud F. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hols technique. Comparison with pulmonary angiography. Radiology 1992; 185: 381-7.
• 85 Remy-Jardin M, Remy J, Deschildre F, Artaud D, Beregi JP, HosseinFoucher C. et al. Diagnosis of pulmonary embolism with spiral CT: comparison with pulmonary angiography and scintigraphy. Radiology 1996; 200: 699-706.
• 86 Goodman LR, Curtin JJ, Mewissen MW, Foley WD, Lipchik RJ, Crain MR. et al. Detection of pulmonary embolism in patients with unresolved clinical and scintigraphic diagnosis: helical CT versus angiography. AJR 1995; 164: 1369-74.
• 87 van Rossum AB, Pattynama PMT, Tjin A, Ton ER, Treurniet FE, Arndt JW, van Eck B. et al. Pulmonary embolism: validation of spiral CT angiography in 149 patients. Radiology 1996; 201: 23-8.
• 88 van Rossum AB, Treurniet FE, Kieft GJ, Smith SJ, Schepers-Bok R. Role of spiral volumetric computed tomographic scanning in the assessment of patients with clinical suspicion of pulmonary embolism and an abnormal ventilation/perfusion lung scan. Thorax 1996; 51: 23-8.
• 89 Sostman HD, Layish DT, Tapson VF, Spritzer CE, DeLong DM, Trotter P. et al. Prospective comparison of helical CT and MR imaging in clinically suspected acute pulmonary embolism. J Magn Reson Imaging 1996; 6: 275-81.
• 90 Mayo JR, Remy-Jardin M, Muller NL, Remy J, Worsley DF, HosseinFoucher C. et al. Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy. Radiology 1997; 205: 447-52.
• 91 Garg K, Welsh CH, Feyerabend AJ, Subber SW, Russ PD, Johnston RJ. et al. Pulmonary embolism: diagnosis with spiral CT and ventilation-perfusion scanning – correlation with pulmonary angiographic results or clinical outcome. Radiology 1998; 208: 201-8.
• 92 Kim KI, Muller NL, Mayo JR. Clinically suspected pulmonary embolism: utility of spiral CT. Radiology 1999; 210: 693-7.
• 93 Drucker EA, Rivitz SM, Shepard JA, Boiselle PM, Trotman-Dickenson B, Welch TJ. et al. Acute pulmonary embolism: assessment of helical CT for diagnosis. Radiology 1998; 209: 235-41.
• 94 Remy-Jardin M, Remy J, Artaud D, Deschildre F, Duhamel A. Peripheral pulmonary arteries: optimization of the spiral CT acquisition protocol. Radiology 1997; 204: 157-63.
• 95 Remy-Jardin M, Remy J, Baghaie F, Fribourg M, Artaud D, Duhamel A. Clinical value of thin collimation in the diagnostic workup of pulmonary embolism. Am J Roentgenol 2000; 175: 407-11.
• 96 Perrier A, Howarth N, Didier D, Unger PF, de Moerloose P, Slosman D. et al. Performances of helical computed tomography in unselected patients with suspected pulmonry embolism. Ann Intern Med. 2001 in Press.
• 97 Dalen JE, Brooks HL, Johnson LW, Meister SG, Szues MM, Dexter L. Pulmonary angiography in acute pulmonary embolism: indications, techniques, and results in 367 patients. Am Heart J 1971; 81: 175-85.
• 98 Mills SR, Jackson DC, Older RA, Heaston DK, Moore AV. The incidence, etiologies, and avoidance of complications of pulmonary angiography in a large series. Radiology 1980; 136: 295-9.
• 99 Perlmutt LM, Braun SD, Newman GE, Oke EJ, Dunnick NR. Pulmonary arteriography in the high risk patient. Radiology 1987; 162: 187-9.
• 100 Stein PD, Athanasoulis C, Alavi A, Greenspan RH, Hales CA, Saltzman HA. et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992; 85: 462-8.
• 101 Hudson ER, Smith TP, McDermott VG, Newman GE, Suhocki PV, Payne CS. et al. Pulmonary angiography performed with iopamidol: complications in 1434 patients. Radiology 1996; 198: 61-5.
• 102 Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386-9.
• 103 Come PC. Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions. Chest 1992; 101: 151S-62.
• 104 Guidelines on diagnosis and management of acute pulmonary embolism.. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21: 1301-36.
• 105 Pruszczyk P, Torbicki A, Pacho R, Chlebus M, Kuch-Wocial A, Pruszynski B. et al. Noninvasive diagnosis of suspected severe pulmonary embolism: transesophageal echocardiography vs spiral CT. Chest 1997; 112: 722-8.
• 106 Vieillard-Baron A, Qanadli SD, Antakly Y, Fourme T, Loubieres Y, Jardin F. et al. Transesophageal echocardiography for the diagnosis of pulmonary embolism with acute cor pulmonale: a comparison with radiological procedures. Intensive Care Med 1998; 24: 429-33.
• 107 Jardin F, Dubourg O, Bourdarias JP. Echocardiographic pattern of acute cor pulmonale. Chest 1997; 111: 209-17.
• 108 McConnell MV, Solomon SD, Rayan ME, Come PC, Goldhaber SZ, Lee RT. Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism. Am J Cardiol 1996; 78: 469-73.
• 109 Perrier A, Tamm C, Unger PF, Lerch R, Sztajzel J. Diagnostic accuracy of Doppler-echocardiography in unselected patients with suspected pulmonary embolism. Int J Cardiol 1998; 65: 101-9.
• 110 Jackson RE, Rudoni RR, Hauser AM, Pascual RG, Hussey ME. Prospective evaluation of two-dimensional transthoracic echocardiography in emergency department patients with suspected pulmonary embolism. Acad Emerg Med 2000; 7: 994-8.
• 111 Nazeyrollas P, Metz D, Chapoutot L, Chabert JP, Maillier B, Maes D. et al. Diagnostic accuracy of echocardiography-Doppler in acute pulmonary embolism. Int J Cardiol 1995; 47: 273-80.
• 112 Steiner P, Lund GK, Debatin JF, Steiner D, Nienaber C, Nicolas V. et al. Acute pulmonary embolism: value of transthoracic and transesophageal echocardiography in comparison with helical CT. AJR 1996; 167: 931-6.
• 113 Bounameaux H, Perrier A. Rapid diagnosis of deep vein thrombosis in symptomatic patients: a comparison between four different diagnostic strategies. Thromb Haemost 1999; 82: 1360-1.
• 114 Pauker SG, Kassirer JP. Clinical application of decision analysis : a detailed illustration. Sem Nucl Med 1978; 8: 324-35.
• 115 van Beek EJ, Schenk BE, Michel BC, van den Ende B, Brandjes DP, van der Heide YT. et al. The role of plasma D-dimers concentration in the exclusion of pulmonary embolism. Br J Haematol 1996; 92: 725-32.
• 116 Morabia A, Steinig-Stamm M, Unger PF, Slosman D, Schneider PA, Perrier A. et al. Applicability of decision analysis to everyday clinical work: a controlled feasibility trial. J Gen Intern Med 1994; 9: 496-502.
• 117 Perrier A, Bounameaux H, Morabia A, de Moerloose P, Slosman D, Unger PF. et al. Contribution of D-dimer plasma measurement and lower-limb venous ultrasound to the diagnosis of pulmonary embolism: a decision analysis model. Am Heart J 1994; 127: 624-35.
• 118 Oudkerk M, van Beek JR, van Putten WLJ, B\’fcller HR. Cost-effectiveness analysis of various strategies in the diagnostic management of pulmonary embolism. Arch Intern Med 1993; 153: 947-54.
• 119 van Erkel AR, van Rossum AB, Bloem JL, Kievit J, Pattynama PM. Spiral CT angiography for suspected pulmonary embolism: a cost-effectiveness analysis. Radiology 1996; 201: 29-36.
• 120 Sanson BJ, Lijmer JG, Mac Gillavry MR, Turkstra F, Prins MH, Buller HR. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. ANTELOPE-Study Group. Thromb Haemost 2000; 83: 199-203.
• 121 Lagerstedt CI, Fagher BO, Olsson CG, Öqvist BW. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet 1985; 2: 515-8.
• 122 Monreal M, Ruiz J, Salvador R, Morera J, Arias A. Recurrent pulmonary embolism. A prospective study. Chest 1989; 95: 976-9.
• 123 Monreal M, Ruiz J, Olazabal A, Aria A, Roca J. Deep venous thrombosis and the risk of pulmonary embolism. A systematic study. Chest 1992; 102: 677-81.
• 124 Philbrick JT, Becker DM. Calf deep venous thrombosis. A wolf in sheep’s clothing ? Arch Intern Med 1988; 148: 2131-8.
• 125 Sijens PE, van Ingen HE, van Beek EJR, Berghout A, Oudkerk M. 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: 156-9.
• 126 Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser K, Rauber K. et al. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997; 96: 882-8.
• 127 Kasper W, Konstantinides S, Geibel A, Olschewski M, Heinrich F, Grosser KD. et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997; 30: 1165-71.
• 128 Goldhaber SZ, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL. et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary reperfusion. Lancet 1993; 341: 507-11.
• 129 Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, Johnsson H, Jorfeldt L. Echocardiography Doppler in pulmonary embolism: right ventricular dysfunction as a predictor of mortality rate. Am Heart J 1997; 134: 479-87.
• 130 Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G. et al. Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation 2000; 101: 2817-22.
• 131 Ribeiro A, Juhlin-Dannfelt A, Brodin LA, Holmgren A, Jorfeldt L. Pulmonary embolism: relation between the degree of right ventricle overload and the extent of perfusion defects. Am Heart J 1998; 135: 868-74.
• 132 Simonneau G, Sors H, Charbonnier B, Page Y, Laaban JP, Azarian R. et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. N Engl J Med 1997; 337: 663-9.
• 133 Low-molecular-weight heparin in the treatment of patients with venous thromboembolism.. The Columbus Investigators. N Engl J Med 1997; 337: 657-62.