The American Journal of Medicine
Volume 121, Issue 7 , Pages 565-571 , July 2008

Challenges in the Diagnosis Acute Pulmonary Embolism

  • Paul D. Stein, MD

      Affiliations

    • Department of Research, St Joseph Mercy Oakland Hospital, Pontiac, Mich
    • Department of Medicine, Wayne State University, Detroit, Mich
    • Corresponding Author InformationRequests for reprints should be addressed to Paul D. Stein, MD, Saint Joseph Mercy Oakland, 44405 Woodward Avenue. Pontiac, MI 48341-5023.
    • ,
  • H. Dirk Sostman, MD

      Affiliations

    • Office of the Dean, Weill Cornell Medical College and Methodist Hospital, Houston, Tex
    • ,
  • Henri Bounameaux, MD

      Affiliations

    • Department of Medicine, University of Geneva, Geneva, Switzerland
    • ,
  • Harry R. Buller, MD

      Affiliations

    • Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
    • ,
  • Thomas L. Chenevert, PhD

      Affiliations

    • Department of Radiology, University of Michigan, Ann Arbor
    • ,
  • James E. Dalen, MD

      Affiliations

    • College of Medicine and College of Public Health, University of Arizona, Tucson
    • ,
  • Lawrence R. Goodman, MD

      Affiliations

    • Department of Radiology, Medical College of Wisconsin, Milwaukee
    • ,
  • Alexander Gottschalk, MD

      Affiliations

    • Department of Radiology, Michigan State University, East Lansing
    • ,
  • Russell D. Hull, MBBS, MSc

      Affiliations

    • Department of Medicine, University of Calgary, Calgary, Alberta, Canada
    • ,
  • Kenneth V. Leeper Jr, MD

      Affiliations

    • Department of Medicine, Emory University, Atlanta, Ga
    • ,
  • Massimo Pistolesi, MD

      Affiliations

    • Department of Critical Care, University of Florence, Florence, Italy
    • ,
  • Gary E. Raskob, PhD

      Affiliations

    • Department of Epidemiology and Medicine, University of Oklahoma Health Sciences Center, Oklahoma City
    • ,
  • Philip S. Wells, MD

      Affiliations

    • Department of Medicine, University of Ottawa and Ottawa Health Research Institute, Ottawa, Canada
    • ,
  • Pamela K. Woodard, MD

      Affiliations

    • Department of Radiology, Washington University, St Louis, Mo.

References 

  1. Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of deep venous thrombosis and acute pulmonary embolism: a systematic review. Ann Intern Med. 2004;140:589–602
  2. Di Nisio M, Squizzato A, Rutjes AW, et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost. 2007;5:296–304
  3. Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med. 2006;119:1048–1055
  4. van Belle A, Büller 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. JAMA. 2006;295:172–179
  5. 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;116:291–299
  6. Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med. 2005;28:1760–1768
  7. 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
  8. Galle C, Papazyan JP, Miron MJ, et al. Prediction of pulmonary embolism extent by clinical findings, D-dimer level and deep vein thrombosis shown by ultrasound. Thromb Haemost. 2001;86:1156–1160
  9. 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;49:1483–1490
  10. Le Gal G, Righini M, Roy PM, et al. Value of D-dimer testing for the exclusion of pulmonary embolism in patients with previous venous thromboembolism. Arch Intern Med. 2006;166:176–180
  11. Chabloz P, Reber G, Boehlen F, et al. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol. 2001;115:150–152
  12. Righini M, Goehring C, Bounameaux H, et al. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med. 2000;109:357–361
  13. Barro C, Bosson JL, Pernod G, et al. Plasma D-dimer testing improves the management of thromboembolic disease in hospitalized patients. Thromb Res. 1999;95:263–269
  14. ten Wolde M, Kraaijenhagen RA, Prins MH, et al. The clinical usefulness of D-dimer testing in cancer patients with suspected deep venous thrombosis. Arch Intern Med. 2002;162:1880–1884
  15. Lee AY, Julian JA, Levine MN, et al. Clinical utility of a rapid whole-blood D-dimer assay in patients with cancer who present with suspected acute deep venous thrombosis. Ann Intern Med. 1999;131:417–423
  16. Di Nisio M, Sohne M, Kamphuisen PW, et al. D-Dimer test in cancer patients with suspected acute pulmonary embolism. J Thromb Haemost. 2005;3:1239–1242
  17. Le Gal G, Bounameaux H. Diagnosing pulmonary embolism: running after the decreasing prevalence of cases among suspected patients. J Thromb Haemost. 2004;2:1244–1246
  18. Morpurgo M, Schmid C. Clinico-pathological correlations in pulmonary embolism: a posteriori evaluation. Progr Respir Res. 1980;13:8–15
  19. Karwinski B, Svendsen E. Comparison of clinical and post-mortem diagnosis of pulmonary embolism. J Clin Pathol. 1989;42:135–139
  20. Sperry KL, Key CR, Anderson RE. Toward a population-based assessment of death due to pulmonary embolism in New Mexico. Hum Pathol. 1990;21:159–165
  21. Stein PD, Henry SW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest. 1995;108:978–981
  22. Task Force Report of the European Society of Cardiology. Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J. 2000;21:1301–1336
  23. Wenger NK, Stein PD, Willis PW. Massive acute pulmonary embolism: the deceivingly non-specific manifestations. JAMA. 1972;220:843–844
  24. Bell WR, Simon TL, DeMets DL. The clinical features of submassive and massive pulmonary emboli. Am J Med. 1977;62:355–360
  25. Stein PD, Willis PW, DeMets DL. History and physical examination in acute pulmonary embolism in patients without pre-existing cardiac or pulmonary disease. Am J Cardiol. 1981;47:218–223
  26. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax. 2003;58:470–484
  27. Qaseem A, Snow V, Barry P, et al. Joint American Academy of Family Physicians/American College of Physicians Panel on Deep venous Thrombosis/Pulmonary Embolism Current Diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of family physicians and the American College of physicians. Ann Intern Med. 2007;146:454–458
  28. Remy-Jardin M, Pistolesi M, Goodman LR, et al. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement of the Fleischner Society. Radiology. 2007;245:315–329
  29. Ranji SR, Shojania KG, Trowbridge RL, et al. Impact of reliance on CT Pulmonary Angiography on diagnosis of pulmonary embolism: a Bayesian analysis. J Hosp Med. 2006;1:81–87
  30. PIOPED Investigators. Value of the ventilation-perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA. 1990;263:2753–2759
  31. Miniati M, Pistolesi M, Marini C, et al. Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Am J Respir Crit Care Med. 1996;154:1387–1393
  32. Chunilal SD, Eikelboom JW, Attia J, et al. Does this patient have pulmonary embolism?. JAMA. 2003;290:2849–2858
  33. Rodger MA, Maser E, Stiell I, et al. The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism. Thromb Res. 2005;116:101–107
  34. Wells PS, Anderson DR, Rodger MA, et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med. 2001;135:98–107
  35. 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
  36. Sanson BJ, Lijmer JG, Mac Gillavry MR, et al. 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
  37. Wells PS, Anderson DR, Marc R, 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
  38. 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;113:269–275
  39. 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;161:92–97
  40. Le Gal G, Righini M, Roy P-M, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med. 2006;144:165–171
  41. Miniati M, Prediletto R, Formichi B, et al. Accuracy of clinical assessment in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med. 1999;159:864–871
  42. Miniati M, Monti S, Bottai M. A structured clinical model for predicting the probability of pulmonary embolism. Am J Med. 2003;114:173–179
  43. Miniati M, Monti S, Bauleo C, et al. A diagnostic strategy for pulmonary embolism based on standardised pretest probability and perfusion lung scanning: a management study. Eur J Nucl Med Mol Imaging. 2003;30:1450–1456
  44. Ollenberg GP, Worsley DF. Effect of patient location on the performance of clinical models to predict pulmonary embolism. Thromb Res. 2006;118:685–690
  45. Miniati M, Bottai M, Monti S. Comparison of 3 clinical models for predicting the probability of pulmonary embolism. Medicine. 2005;84:107–114(Baltimore)
  46. Kline JA, Mitchell AM, Kaberhel C, et al. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost. 2004;2:1247–1255
  47. Rodger MA, Raymond F, Stiell I, et al. Development and validation of a simple clinical prediction rule to exclude pulmonary embolism. Blood. 1999;94(Suppl):27;Abstract
  48. Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997;350:1795–1798
  49. Gibson NS, Sohne M, Kruip MJ, et al. on behalf of the Christopher study investigators (Further validation and simplification of the Wells clinical decision rule in pulmonary embolism). Thromb Haemost. 2008;99:229–234
  50. Miller AC, Boldy DA. Pulmonary embolism guidelines: will they work?. Thorax. 2003;58:463
  51. Stein PD, Fowler SE, Goodman LR, et al. PIOPED II Investigators Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354:2317–2327
  52. Stein PD, Kayali F, Hull RD. Spiral CT, for the diagnosis of acute pulmonary embolism. Thromb Haemost. 2007;98:713–720
  53. Anderson DR, Kovacs MJ, Dennie C, et al. Use of spiral computed tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department. J Emerg Med. 2005;29:399–404
  54. Musset D, Parent F, Meyer G, et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet. 2002;360:1914–1920
  55. Kalva SP, Jagannathan JP, Hahn PF, Wicky ST. Venous thromboembolism: indirect CT venography during CT pulmonary angiography—should the pelvis be imaged?. Radiology. 2008;246:605–611
  56. Stein PD, Beemath A, Goodman LR, et al. Outcome studies of pulmonary embolism versus accuracy: they do not equate. Thromb Haemost. 2006;96:107–108
  57. Brenner DJ, Hall EJ. Computed tomography-an increasing source of radiation exposure. N Engl J Med. 2007;357:2277–2284
  58. Goodman LR, Stein PD, Beemath A, et al. CT venography: continuous helical images versus reformatted discontinuous images using PIOPED II data. Am J Roentgenol. 2007;189:409–412
  59. Goodman LR, Stein PD, Matta F, et al. CT Venography and compression ultrasound are diagnostically equivalent: data from PIOPED II. Am J Roentgenol. 2007;189:1071–1076
  60. Amis ES, Butler PF, Applegate KE, et al. American College of Radiology (American College of Radiology white paper on radiation dose in medicine). J Am Coll Radiol. 2007;4:272–284
  61. Parker MS, Hui FK, Camacho MA. Female breast radiation exposure during CT pulmonary angiography. Am J Roentgenol. 2005;185:1228–1233
  62. Einstein AJ, Henzlova MJ, Rajagopalan S. Estimating risk of cancer associated with radiation exposure from 64-slice computed tomography coronary angiography. JAMA. 2007;298:317–323
  63. Milne ENC. Female breast radiation exposure. Am J Roentgenenol. 2006;186:E24
  64. Radiation dose to patients from radiopharmaceuticals. (addendum 2 to ICRP publication 53) Ann ICRP. 1998;28:1–126
  65. Anderson DR, Kahn SR, Rodger MA, et al. Computerized tomographic pulmonary angiography versus ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. J Am Med Assoc. 2007;298:2743–2753
  66. Sostman HD, Stein PD, Gottschalk A, et al. Acute pulmonary embolism: sensitivity and specificity of ventilation-perfusion scintigraphy in PIOPED II. Radiology. 2008;246:941–946Epub 2008 Jan 14
  67. Gottschalk A, Stein PD, Goodman LR, et al. Overview of prospective investigation of pulmonary embolism diagnosis II. Semin Nucl Med. 2002;32:173–182
  68. Forbes KP, Reid JH, Murchison JT. Do preliminary chest x-ray findings define the optimum role of pulmonary scintigraphy in suspected pulmonary embolism?. Clin Radiol. 2001;56:397–400
  69. Goldberg SN, Palmer EL, Scott JA, et al. Pulmonary embolism: prediction of the usefulness of initial ventilation–perfusion scanning with chest radiographic findings. Radiology. 1994;193:801–805
  70. Stein PD, Alavi A, Gottschalk A, et al. Usefulness of non-invasive diagnostic tools for diagnosis of acute pulmonary embolism in patients with a normal chest radiograph. Am J Cardiol. 1991;67:1117–1120
  71. Gottschalk A, Stein PD, Sostman HD, et al. Very low probability interpretation of ventilation-perfusion lung scans in combination with low probability clinical assessment reliably excludes pulmonary embolism: Data from PIOPED II. J Nucl Med. 2007;48:1411–1415
  72. Kipper MS, Moser KM, Kortman KE, et al. Long-term follow-up in patients with suspected pulmonary embolism and a normal lung scan. Chest. 1982;82:411–415
  73. Hull RD, Raskob GE, Coates G, et al. Clinical validity of a normal perfusion lung scan in patients with suspected pulmonary embolism. Chest. 1990;97:23–26
  74. Stein PD, Terrin ML, Gottschalk A, et al. Value of ventilation/perfusion scans compared to perfusion scans alone in acute pulmonary embolism. Am J Cardiol. 1992;69:1239–1241
  75. Meaney JF, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med. 1997;336:1422–1427
  76. Oudkerk M, van Beek EJ, Wielopolski P, et al. Comparison of contrast-enhanced magnetic resonance angiography and conventional pulmonary angiography for the diagnosis of pulmonary embolism: a prospective study. Lancet. 2002;359:1643–1647
  77. Gupta A, Frazer CK, Ferguson JM, et al. Acute pulmonary embolism: diagnosis with MR angiography. Radiology. 1999;210:353–359
  78. Blum A, Bellou A, Guillemin F, et al. GENEPI study group (Performance of magnetic resonance angiography in suspected acute pulmonary embolism). Thromb Haemost. 2005;93:503–511
  79. Obernosterer A, Aschauer M, Portugaller H, et al. Three-dimensional gadolinium-enhanced magnetic resonance angiography used as a “one-stop shop” imaging procedure for venous thromboembolism: a pilot study. Angiology. 2005;56:423–430
  80. U.S.Food and Drug Administration, Healthcare professional sheet. Gadolinium-containing contrast agents for magnetic resonance imaging (MRI). (marketed as Omniscan, OptiMARK, Magnevist, ProHance and Multihance) http://www.fda.gov/cder/drug/InfoSheets/HCP/gccaHCP.htmAccessed June 23, 2006
  81. Cowper SE. International Center for Nephrogenic Fibrosing Dermopathy Research (ICNFDR). http://www.pathmax.com/dermweb/Accessed March 27, 2007
  82. Kanal E, Barkovich AJ, Bell C, et al. ACR Blue Ribbon Panel on MR Safety ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol. 2007;188:1447–1474
  83. Krueger JJ, Ewert P, Yilmaz S, et al. Magnetic resonance imaging-guided balloon angioplasty of coarctation of the aorta: a pilot study. Circulation. 2006;113:1093–1100
  84. Moody AR, Liddicoat A, Krarup K. Magnetic resonance pulmonary angiography and direct imaging of embolus for the detection of pulmonary emboli. Invest Radiol. 1997;32:431–440
  85. Schiebler ML, Holland GA, Hatabu H, et al. Suspected pulmonary embolism: prospective evaluation with pulmonary MR angiography. Radiology. 1993;189:125–131
  86. Grist TM, Sostman HD, MacFall JR, et al. Pulmonary angiography with MR imaging: preliminary clinical experience. Radiology. 1993;189:523–530
  87. Sostman HD, Layish DT, Tapson VF, et al. Prospective comparison of helical CT and MR imaging in clinically suspected acute pulmonary embolism. J Magn Reson Imaging. 1996;6:275–281
  88. Winer-Muram HT, Rydberg J, Johnson MS, et al. Suspected acute pulmonary embolism: evaluation with multi-detector row CT versus digital subtraction pulmonary arteriography. Radiology. 2004;233:806–815
  89. Wittram C, Waltman AC, Shepard JA, et al. Discordance between CT and angiography in the PIOPED II study. Radiology. 2007;244:883–889

PII: S0002-9343(08)00253-2

doi: 10.1016/j.amjmed.2008.02.033

The American Journal of Medicine
Volume 121, Issue 7 , Pages 565-571 , July 2008

Article Tools