Download PDF
Hamostaseologie 2018; 38(01): 11-21
DOI: 10.5482/HAMO-17-07-0023
Review
Schattauer GmbH

Diagnosis of acute Pulmonary Embolism

Diagnose der akuten Lungenembolie
Marc Righini
1   Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
,
Helia Robert-Ebadi
1   Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland
› Author Affiliations
Further Information

Publication History

received: 13 July 2017

accepted in revised form: 05 December 2017

Publication Date:
26 February 2018 (online)

Also available at
   Permissions and Reprints

Summary

During the last three decades, considerable advances in the management of patients with suspected pulmonary embolism (PE) have improved diagnostic accuracy and made management algorithms safer, easier to use and well standardized. These diagnostic algorithms are mainly based on the assessment of clinical pretest probability, D-Dimer measurement and imaging tests, mainly computed tomography pulmonary angiography (CTPA). These diagnostic algorithms allow a safe and cost-effective diagnosis for most patients with suspected PE.

In this review, we discuss current existing evidence for PE diagnosis, the challenge of diagnosing PE in special patient populations, as well as novel imaging tests for PE diagnosis.

Zusammenfassung

In den vergangenen drei Jahrzehnten haben erhebliche Fortschritte bei der Diagnostik von Patienten mit Verdacht auf Lungenembolie (LE) zu einer Verbesserung der Diagnosesicherheit geführt. Dadurch wurden die diagnostischen Algorithmen sicherer und einfacher in der Anwendung und sind mittlerweile zuverlässig standardisiert. Diese diagnostischen Algorithmen beruhen vor allem auf der Beurteilung der klinischen Prä-Test-Wahrscheinlichkeit, der D-Dimer-Messung und bildgebenden Untersuchungen, insbesondere der Computertomografie-Pulmonalangiografie (CTPA). Diese diagnostischen Algorithmen erlauben bei den meisten Patienten mit Verdacht auf LE eine sichere und wirtschaftliche Diagnose.

In dieser Übersicht diskutieren wir die aktuell vorliegende Evidenz für die LE Diagnostik, die Herausforderung einer LE-Diagnose in speziellen Patientenkollektiven sowie neuartige bildgebende Verfahren für die LE-Diagnose.

Keywords

Pulmonary embolism - pre-test clinical probability - D-dimer - age-adjusted D-dimer cutoff - computed tomography pulmonary angiography

Schlüsselwörter

Lungenembolie - klinische Prä-Test-Wahrscheinlichkeit - D-Dimer - altersadjustierter D-Dimer-Schwellenwert - Computertomografie-Pulmonalangiografie
 

  • References

  • 1 Le Gal G, Bounameaux H. Diagnosing pulmonary embolism: running after the decreasing prevalence of cases among suspected patients. Journal of thrombosis and haemostasis : JTH 2004; 02 (08) 1244-1246.
    CrossrefPubMedGoogle Scholar
  • 2 Konstantinides SV. Trends in incidence versus case fatality rates of pulmonary embolism: Good news or bad news?. Thrombosis and haemostasis 2016; 115 (02) 233-235.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Archives of internal medicine 2011; 171 (09) 831-837.
    PubMedGoogle Scholar
  • 4 Righini M, Le Gal G, Aujesky D, Roy PM, Sanchez O, Verschuren F. et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. The Lancet 2008; 371 (9621): 1343-1352.
    CrossrefPubMedGoogle Scholar
  • 5 van Belle A, Buller HR, Huisman MV, Huisman PM, Kaasjager K, Kamphuisen PW. et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. Jama 2006; 295 (02) 172-179.
    CrossrefPubMedGoogle Scholar
  • 6 Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. Journal of thrombosis and haemostasis: JTH 2004; 02: 1247-1255.
    CrossrefPubMedGoogle Scholar
  • 7 Kline JA, Courtney DM, Kabrhel C, Moore CL, Smithline HA, Plewa MC. et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. Journal of thrombosis and haemostasis: JTH 2008; 06 (05) 772-780.
    CrossrefPubMedGoogle Scholar
  • 8 Righini M, Le Gal G, Perrier A, Bounameaux H. More on: clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. Journal of thrombosis and haemostasis: JTH 2005; 03 (01) 188-189. author reply 90-91.
    CrossrefPubMedGoogle Scholar
  • 9 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?. Archives of internal medicine 2000; 160 (04) 512-516.
    CrossrefPubMedGoogle Scholar
  • 10 The PIOPED Investigators. Value of the ventilation-perfusion scan in acute pulmonary embolism. JAMA 1990; 263: 2753-2759.
    CrossrefPubMedGoogle Scholar
  • 11 Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H. et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006; 144 (03) 165-171.
    CrossrefPubMedGoogle Scholar
  • 12 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. Thrombosis and haemostasis 2000; 83 (03) 416-420.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Ceriani E, Combescure C, Le Gal G, Nendaz M, Perneger T, Bounameaux H. et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. Journal of thrombosis and haemostasis: JTH 2010; 08 (05) 957-970.
    PubMedGoogle Scholar
  • 14 Lucassen W, Geersing GJ, Erkens PM, Reitsma JB, Moons KG, Buller H. et al. Clinical decision rules for excluding pulmonary embolism: a meta-analysis. Ann Intern Med 2011; 155 (07) 448-460.
    CrossrefPubMedGoogle Scholar
  • 15 Douma RA, Mos IC, Erkens PM, Nizet TA, Durian MF, Hovens MM. et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med 2011; 154 (11) 709-718.
    CrossrefPubMedGoogle Scholar
  • 16 Di Nisio M, Squizzato A, Rutjes AW, Buller HR, Zwinderman AH, Bossuyt PM. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. Journal of thrombosis and haemostasis: JTH 2007; 05: 296-304.
    CrossrefPubMedGoogle Scholar
  • 17 Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R. et al. D-Dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Intern Med 2004; 140 (08) 589-602.
    CrossrefPubMedGoogle Scholar
  • 18 Carrier M, Righini M, Djurabi RK, Huisman MV, Perrier A, Wells PS. et al. VIDAS D-dimer in combination with clinical pre-test probability to rule out pulmonary embolism. A systematic review of management outcome studies. Thrombosis and haemostasis 2009; 101 (05) 886-892.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 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 (9148) 190-195.
    CrossrefPubMedGoogle Scholar
  • 20 Perrier A, Roy PM, Aujesky D, Chagnon I, Howarth N, Gourdier AL. 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 (05) 291-299.
    CrossrefPubMedGoogle Scholar
  • 21 Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL. et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med 2005; 352 (17) 1760-1768.
    CrossrefPubMedGoogle Scholar
  • 22 Le Gal G, Righini M, Wells PS. D-dimer for pulmonary embolism. JAMA 2015; 313 (16) 1668-1669.
    CrossrefPubMedGoogle Scholar
  • 23 Favaloro EJ, Franchini M, Lippi G. Aging hemostasis: changes to laboratory markers of hemostasis as we age-a narrative review. Seminars in thrombosis and hemostasis 2014; 40 (06) 621-633.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 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 (05) 357-361.
    CrossrefPubMedGoogle Scholar
  • 25 Robert-Ebadi H, Bertoletti L, Combescure C, Le Gal G, Bounameaux H, Righini M. Effects of impaired renal function on levels and performance of D-dimer in patients with suspected pulmonary embolism. Thrombosis and haemostasis 2014; 112 (03) 614-620.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Douma RA, le Gal G, Sohne M, Righini M, Kamphuisen PW, Perrier A. et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. Bmj 2010; 340: c1475.
    CrossrefPubMedGoogle Scholar
  • 27 Righini M, Van Es J, Den Exter PL, Roy PM, Verschuren F, Ghuysen A. et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014; 311 (11) 1117-1124.
    CrossrefPubMedGoogle Scholar
  • 28 Raja AS, Greenberg JO, Qaseem A, Denberg TD, Fitterman N, Schuur JD. et al. Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2015; 163 (09) 701-711.
    CrossrefPubMedGoogle Scholar
  • 29 Ercan S, Ozkan S, Yucel N, Orcun A. Establishing reference intervals for D-dimer to trimesters. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet 2015; 28 (08) 983-987.
    PubMedGoogle Scholar
  • 30 Grossman KB, Arya R, Peixoto AB, Akolekar R, Staboulidou I, Nicolaides KH. Maternal and pregnancy characteristics affect plasma fibrin monomer complexes and D-dimer reference ranges for venous thromboembolism in pregnancy. American journal of obstetrics and gynecology 2016; 215 (04) 466 e1–8.
    PubMedGoogle Scholar
  • 31 van der Hulle T, Cheung WY, Kooij S, Beenen LFM, van Bemmel T, van Es J. et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet 2017; 390 (10091) 289-297.
    CrossrefPubMedGoogle Scholar
  • 32 Perrier A, Howarth N, Didier D, Loubeyre P, Unger PF, de Moerloose P. et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med 2001; 135 (02) 88-97.
    CrossrefPubMedGoogle Scholar
  • 33 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 (03) 227-232.
    CrossrefPubMedGoogle Scholar
  • 34 Musset D, Parent F, Meyer G, Maitre S, Girard P, Leroyer C. et al. Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study. Lancet 2002; 360: 1914-1920.
    CrossrefPubMedGoogle Scholar
  • 35 Le Gal G, Righini M, Wells PS. Computed Tomographic Pulmonary Angiography for Pulmonary Embolism. JAMA 2015; 314 (01) 74-75.
    CrossrefPubMedGoogle Scholar
  • 36 Ghaye B, Szapiro D, Mastora I, Delannoy V, Duhamel A, Remy J. et al. Peripheral pulmonary arteries: how far in the lung does multi-detector row spiral CT allow analysis?. Radiology 2001; 219 (03) 629-636.
    CrossrefPubMedGoogle Scholar
  • 37 Anderson DR, Kahn SR, Rodger MA, Kovacs MJ, Morris T, Hirsch A. et al. Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. Jama 2007; 298 (23) 2743-2753.
    CrossrefPubMedGoogle Scholar
  • 38 Mos IC, Klok FA, Kroft LJ, DER A, Dekkers OM, Huisman MV. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. Journal of thrombosis and haemostasis: JTH 2009; 07 (09) 1491-1498.
    CrossrefPubMedGoogle Scholar
  • 39 Moores L, Kline J, Portillo AK, Resano S, Vicente A, Arrieta P. et al. Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism. Journal of thrombosis and haemostasis: JTH 2016; 14 (01) 114-120.
    CrossrefPubMedGoogle Scholar
  • 40 Le Gal G, Righini M, Parent F, van Strijen M, Couturaud F. Diagnosis and management of subsegmental pulmonary embolism. Journal of thrombosis and haemostasis: JTH 2006; 04 (04) 724-731.
    CrossrefPubMedGoogle Scholar
  • 41 Yazdani M, Lau CT, Lempel JK, Yadav R, El-Sherief AH, Azok JT. et al. Historical Evolution of Imaging Techniques for the Evaluation of Pulmonary Embolism. Radiographics: a review publication of the Radiological Society of North America, Inc 2015; 35 (04) 1245-1262.
    CrossrefPubMedGoogle Scholar
  • 42 Bauer RW, Frellesen C, Renker M, Schell B, Lehnert T, Ackermann H. et al. Dual energy CT pulmonary blood volume assessment in acute pulmonary embolism – correlation with D-dimer level, right heart strain and clinical outcome. Eur Radiol 2011; 21 (09) 1914-1921.
    CrossrefPubMedGoogle Scholar
  • 43 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. Journal of Nuclear Medicine 1993; 34: 1119-1126.
    PubMedGoogle Scholar
  • 44 Le Gal G, Righini M, Sanchez O, Roy PM, Baba-Ahmed M, Perrier A. et al. A positive compression ultrasonography of the lower limb veins is highly predictive of pulmonary embolism on computed tomography in suspected patients. Thrombosis and haemostasis 2006; 95 (06) 963-966.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Da Costa JRodrigues, Alzuphar S, Combescure C, Le Gal G, Perrier A. Diagnostic characteristics of lower limb venous compression ultrasonography in suspected pulmonary embolism: a meta-analysis. Journal of thrombosis and haemostasis: JTH 2016; 14 (09) 1765-1772.
    CrossrefPubMedGoogle Scholar
  • 46 Stein PD, Chenevert TL, Fowler SE, Goodman LR, Gottschalk A, Hales CA. et al. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III). Ann Intern Med 2010; 152 (07) 434-443. W142-W143.
    CrossrefPubMedGoogle Scholar
  • 47 Revel MP, Sanchez O, Couchon S, Planquette B, Hernigou A, Niarra R. et al. Diagnostic accuracy of magnetic resonance imaging for an acute pulmonary embolism: results of the ‘IRM-EP’ study. Journal of thrombosis and haemostasis: JTH 2012; 10 (05) 743-750.
    CrossrefPubMedGoogle Scholar
  • 48 Zhou M, Hu Y, Long X, Liu D, Liu L, Dong C. et al. Diagnostic performance of magnetic resonance imaging for acute pulmonary embolism: a systematic review and meta-analysis. Journal of thrombosis and haemostasis: JTH 2015; 13 (09) 1623-1634.
    CrossrefPubMedGoogle Scholar
  • 49 Bajc M, Jonson B. Ventilation/Perfusion SPECT for Diagnosis of Pulmonary Embolism and Other Diseases. International journal of molecular imaging 2011; 2011: 682949.
    PubMedGoogle Scholar
  • 50 Phillips JJ, Straiton J, Staff RT. Planar and SPECT ventilation/perfusion imaging and computed tomography for the diagnosis of pulmonary embolism: A systematic review and meta-analysis of the literature, and cost and dose comparison. European journal of radiology 2015; 84 (07) 1392-1400.
    CrossrefPubMedGoogle Scholar
  • 51 Bajc M, Neilly JB, Miniati M, Schuemichen C, Meignan M, Jonson B. EANM guidelines for ventilation/perfusion scintigraphy : Part 2. Algorithms and clinical considerations for diagnosis of pulmonary emboli with V/P(SPECT) and MDCT. European journal of nuclear medicine and molecular imaging 2009; 36 (09) 1528-1538.
    CrossrefPubMedGoogle Scholar
  • 52 Stein PD, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD. et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med 2006; 354 (22) 2317-2327.
    CrossrefPubMedGoogle Scholar
  • 53 Begemann PG, Bonacker M, Kemper J, Guthoff AE, Hahn KE, Steiner P. et al. Evaluation of the deep venous system in patients with suspected pulmonary embolism with multi-detector CT: a prospective study in comparison to Doppler sonography. Journal of computer assisted tomography 2003; 27 (03) 399-409.
    CrossrefPubMedGoogle Scholar
  • 54 Rademaker J, Griesshaber V, Hidajat N, Oestmann JW, Felix R. Combined CT pulmonary angiography and venography for diagnosis of pulmonary embolism and deep vein thrombosis: radiation dose. Journal of thoracic imaging 2001; 16 (04) 297-299.
    CrossrefPubMedGoogle Scholar
  • 55 Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Perrier A. et al. Value of D-dimer testing for the exclusion of pulmonary embolism in patients with previous venous thromboembolism. Archives of internal medicine 2006; 166 (02) 176-180.
    CrossrefPubMedGoogle Scholar
  • 56 Kahn SR, Shrier I, Julian JA, Ducruet T, Arsenault L, Miron MJ. et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149 (10) 698-707.
    CrossrefPubMedGoogle Scholar
  • 57 Klok FA, Tijmensen JE, Haeck ML, van Kralingen KW, Huisman MV. Persistent dyspnea complaints at long-term follow-up after an episode of acute pulmonary embolism: results of a questionnaire. Eur J Intern Med 2008; 19 (08) 625-629.
    CrossrefPubMedGoogle Scholar
  • 58 Le Gal G, Kovacs MJ, Carrier M, Do K, Kahn SR, Wells PS. et al. Validation of a diagnostic approach to exclude recurrent venous thromboembolism. Journal of thrombosis and haemostasis: JTH 2009; 07 (05) 752-759.
    CrossrefPubMedGoogle Scholar
  • 59 Hamadah A, Alwasaidi T, LEG G, Carrier M, Wells PS, Scarvelis D. et al. Baseline imaging after therapy for unprovoked venous thromboembolism: a randomized controlled comparison of baseline imaging for diagnosis of suspected recurrence. Journal of thrombosis and haemostasis: JTH 2011; 09 (12) 2406-2410.
    CrossrefPubMedGoogle Scholar
  • 60 Stein PD, Matta F. Noninvasive imaging in pulmonary embolism according to age and gender. Clin Appl Thromb Hemost 2014; 20 (02) 143-146.
    CrossrefPubMedGoogle Scholar
  • 61 Carrier M, Righini M, Wells PS, Perrier A, Anderson DR, Rodger MA. et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. Journal of thrombosis and haemostasis: JTH 2010; 08 (08) 1716-1722.
    CrossrefPubMedGoogle Scholar
  • 62 Carrier M, Kimpton M, LEG G, Kahn SR, Kovacs MJ, Wells PS. et al. The management of a sub-segmental pulmonary embolism: a cross-sectional survey of Canadian thrombosis physicians. Journal of thrombosis and haemostasis: JTH 2011; 09 (07) 1412-1415.
    CrossrefPubMedGoogle Scholar
  • 63 den Exter PL, van Es J, Klok FA, Kroft LJ, Kruip MJ, Kamphuisen PW. et al. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood 2013; 122 (07) 1144-1149. quiz 329.
    CrossrefPubMedGoogle Scholar
  • 64 Carrier M, Righini M, Le Gal G. Symptomatic subsegmental pulmonary embolism: what is the next step? Journal of thrombosis and haemostasis. JTH 2012; 10 (08) 1486-1490.
    PubMedGoogle Scholar
  • 65 Remy-Jardin M, Pistolesi M, Goodman LR, Gefter WB, Gottschalk A, Mayo JR. et al. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner Society. Radiology 2007; 245 (02) 315-329.
    CrossrefPubMedGoogle Scholar
  • 66 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149 (02) 315-352.
    CrossrefPubMedGoogle Scholar
  • 67 Klok FA, Mos IC, Nijkeuter M, Righini M, Perrier A, Le Gal G. et al. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Archives of internal medicine 2008; 168 (19) 2131-2136.
    CrossrefPubMedGoogle Scholar
  • 68 Gibson NS, Sohne M, Kruip MJ, Tick LW, Gerdes VE, Bossuyt PM. et al. Further validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thrombosis and haemostasis 2008; 99 (01) 229-234.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 69 Righini M, Perrier A, De Moerloose P, Bounameaux H. D-Dimer for venous thromboembolism diagnosis: 20 years later. Journal of thrombosis and haemostasis: JTH 2008; 06 (07) 1059-1071.
    CrossrefPubMedGoogle Scholar