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Clinical Probability and D-Dimer Testing

  • Chapter
Management of Acute Pulmonary Embolism

Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

In order to address the well-known inadequacies in diagnostic imaging for pulmonary embolism (PE), health care providers can utilize pretest probability estimates in conjunction with the likelihood ratios of diagnostic tests. This approach helps define more accurately the posttest probability of a disease with a given imaging result. In the case of PE, we have the benefit of proven clinical prediction rules to help assess the pretest probability. Furthermore, the D-dimer test, which measures the degradation product of a cross-linked fibrin blood clot, can also be employed in diagnostic algorithms. It is, however, important to keep in mind that although all D-dimer tests lie on the same receiver operating characteristic curve, some have higher sensitivity than others. Thus, when patients are clinically classified as low-probability, moderate-sensitivity D-dimer tests can be performed next, and a negative result will suffice to rule out PE. Because the negative likelihood ratio with these tests is approx 0.20, the patient’s pretest probability of PE must be less than 10% to rule out PE with a negative D-dimer. If, on the other hand, a high-sensitivity D-dimer test is used in patients who have a low or moderate probability of PE, are PE-unlikely by the Wells model, or low- to moderate-probability by the Wicki clinical model, the physician can avoid the need for diagnostic imaging when the D-dimer is negative. In this latter case, the likelihood ratio of 0.06 with the high-sensitivity D-dimer implies that, if patients have a pretest probability of no more than 22%, a negative D-dimer will negate the need for diagnostic imaging. Importantly, combining D-dimer and pretest probability not only allows selection of patients appropriate for diagnostic testing, but also helps interpret the imaging test result as potentially false-negative or false-positive, and thus allows for standardization of the diagnostic workup of PE.

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References

  1. Schluger N, Henschke C, King T, et al. Diagnosis of pulmonary embolism at a large teaching hospital. J Thorac Imaging 1994;9:180–184.

    Article  PubMed  CAS  Google Scholar 

  2. Berghout A, Oudkerk M, Hicks SG, Teng TH, Pillay M, Buller HR. Active implementation of a consenus strategy improves diagnosis and management in suspected pulmonary embolism. Q J Med 2000;93:335–340.

    CAS  Google Scholar 

  3. Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States, 1979–1998. An analysis using multiple-cause mortality data. Arch Intern Med 2003;163:1711–1717.

    Article  PubMed  Google Scholar 

  4. Stein PD, Athanasoulis C, Alavi A, et al. Complications and validity of pulmonary angiography in acute pulmonary embolism. Circulation 1992;85:462–468.

    PubMed  CAS  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. Henry JW, Relyea B, Stein PD. Continuing risk of thromboemboli among patients with normal pulmonary angiograms. Chest 1995;107:1375–1378.

    PubMed  CAS  Google Scholar 

  7. 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;98:891–899.

    PubMed  CAS  Google Scholar 

  8. Remy-Jardin M, Remy J, Artraud D, Fribourg M, Beregi JP. Spiral CT of pulmonary embolism: diagnostic approach, interpretive pitfalls and current indications. Eur Radiol 1998;8:1376–1390.

    Article  PubMed  CAS  Google Scholar 

  9. Rathbun SW, Raskob G, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med 2000;132:227–232.

    PubMed  CAS  Google Scholar 

  10. Forgie MA, Wells PS, Wells G, Millward S. A systematic review of the accuracy of helical CT in the diagnosis of acute pulmonary embolism. Blood 1997;90:3223.

    Google Scholar 

  11. Hayashino Y, Goto M, Noguchi Y, Fukui T. Ventilation-perfusion scanning and helical CT in suspected pulmonary embolism: meta-analysis of diagnostic performance. Radiology 2005;234:740–748.

    Article  PubMed  Google Scholar 

  12. Perrier A, Roy PM, Sanchez O, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med 2005;352:1760–1768.

    Article  PubMed  CAS  Google Scholar 

  13. Mayo JR, Remy-Jardin M, Muller NL, et al. Pulmonary embolism: prospective comparison of spiral CT with ventilation-perfusion scintigraphy. Radiology 1997;205:447–452.

    PubMed  CAS  Google Scholar 

  14. Shah AA, Davis SD, Gamsu G, Intriere L. Parenchymal and pleural findings in patients with and patients without acute pulmonary embolism detected at spiral CT. Radiology 1999;211:147–153.

    PubMed  CAS  Google Scholar 

  15. Stein PD, Saltzman HA, Weg JG. Clinical characteristics of patients with acute pulmonary embolism. Am J Cardiol 1991;68:1723–1724.

    Article  PubMed  CAS  Google Scholar 

  16. Stein PD, Terrin ML, Hales CA, 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.

    Article  PubMed  CAS  Google Scholar 

  17. Susec O, Boudrow D, Kline JA. The clinical features of acute pulmonary embolism in ambulatory patients. Acad Emerg Med 1997;4:891–897.

    Article  PubMed  Google Scholar 

  18. Manganelli D, Palla A, Donnamaria V, Giuntini C. Clinical features of pulmonary embolism. Doubts and certainties. Chest 1996;107(1 Suppl):25S–32S.

    Google Scholar 

  19. Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester study. Arch Intern Med 1991;151:933–938.

    Article  PubMed  Google Scholar 

  20. Anderson FA Jr, Wheeler HB. Venous thromboembolism. Risk factors and prophylaxis. Clin Chest Med 1995;16:235–251.

    PubMed  Google Scholar 

  21. Anderson FA Jr, Wheeler HB. Physician practices in the management of venous thromboembolism: a community-wide survey. J Vasc Surg 1992;15:707–714.

    Google Scholar 

  22. 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.

    PubMed  CAS  Google Scholar 

  23. Hull RD, Raskob G, Carter CJ, et al. Pulmonary embolism in outpatients with pleuritic chest pain. Arch Intern Med 1988;148:838–844.

    Article  PubMed  CAS  Google Scholar 

  24. Stein PD, Dalen JE, McIntyre KM, Sasahara AA, Wenger NK, Willis PW III. The electrocardiogram in acute pulmonary embolism. Prog Cardiovasc Dis 1975;17:247–257.

    Article  PubMed  CAS  Google Scholar 

  25. Ferrari E, Imbert A, Chevalier T, Mihoubi A, Morand P, Baudouy M. The ECG in pulmonary embolism. Predictive value of negative T waves in precordial leads—80 case reports. Chest 1997;111:537–543.

    PubMed  CAS  Google Scholar 

  26. Rodger MA, Makropoulos D, Turek M, et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol 2000;86:807–809.

    Article  PubMed  CAS  Google Scholar 

  27. McFarlane MJ, Imperiale TF. Use of the alveolar-arterial oxygen gradient in the diagnosis of pulmonary embolism. Am J Med 1994;96:57–62.

    Article  PubMed  CAS  Google Scholar 

  28. Stein PD, Goldhaber SZ, Henry JW. Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism. Chest 1995;107:139–143.

    PubMed  CAS  Google Scholar 

  29. Stein PD, Goldhaber SZ, Henry JW, Miller AC. Arterial blood gas analysis in the assessment of suspected acute pulmonary embolism. Chest 1996;109:78–81.

    PubMed  CAS  Google Scholar 

  30. Rodger MA, Carrier MC, Jones GN, et al. Diagnostic value of arterial blood gas measurement in suspected pulmonary embolism. Am J Respir Crit Care Med 2000;162:2105–2108.

    PubMed  CAS  Google Scholar 

  31. 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.

    Article  Google Scholar 

  32. Perrier A, Desmarais S, Miron MJ, et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999;353:190–195.

    Article  PubMed  CAS  Google Scholar 

  33. Richardson WS. Where do pretest probabilities come from? ACP J Club 1999;4:68–69.

    CAS  Google Scholar 

  34. Jackson RE, Rudoni RR, Pascual R. Emergency physician assessment of the pretest probability of pulmonary embolism. Acad Emerg Med 1999;4:891–897.

    Google Scholar 

  35. Rosen MP, Sands DZ, Morris J, Drake W, Davis RB. Does a physician’s ability to accurately assess the likelihood of pulmonary embolism increase with training? Acad Med 2000;75:1199–1205.

    Article  PubMed  CAS  Google Scholar 

  36. Sanson BJ, Lijmer JG, MacGillavry MRM, Turkstra F, Prins MH, Buller HR. Comparison of a clinical probability estimate and two clinical models in patients with suspected pulmonary embolism. Thromb Haemost 2000;83:199–203.

    PubMed  CAS  Google Scholar 

  37. 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.

    PubMed  CAS  Google Scholar 

  38. 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.

    PubMed  CAS  Google Scholar 

  39. Wolf SJ, McCubbin TR, Feldhaus KM, Faragher JP, Adcock DM. Prospective validation of Wells criteria in the evaluation of patients with suspected pulmonary embolism. Ann Emerg Med 2004;44:503–510.

    Article  PubMed  Google Scholar 

  40. Bosson JL, Barro C, Satger B, Carpentier PH, Polack B, Pernod G. Quantitative high D-dimer value is predictive of pulmonary embolism occurrence independently of clinical score in a well-defined low risk factor population. J Thromb Haemost 2005;3:93–99.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  42. Wicki J, Perneger TV, Junod AF, Bounameaux H, Perrier A. Assessing clinical probability of pulmonary embolism in the emergency ward: a simple score. Arch Intern Med 2001;161:92–97.

    Article  PubMed  CAS  Google Scholar 

  43. Wicki J, Perrier A, Pemeger TV, Bounameaux H, Junod AF. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost 2000;84:548–552

    PubMed  CAS  Google Scholar 

  44. 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.

    Article  PubMed  Google Scholar 

  45. Kline JA, Webb WB, Jones AE, Hernandez-Nino J. Impact of a rapid rule-out protocol for pulmonary embolism on the rate of screening, missed cases, and pulmonary vascular imaging in an urban US emergency department. Ann Emerg Med 2004;44:490–502.

    Article  PubMed  Google Scholar 

  46. 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. J Thromb Haemost 2004;2:1247–1255.

    Article  PubMed  CAS  Google Scholar 

  47. Hyers TM. Venous thromboembolism. Am J Respir Crit Care Med 1999;159:1–14.

    PubMed  CAS  Google Scholar 

  48. 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.

    Article  PubMed  Google Scholar 

  49. Bosson JL, Barro C, Satger B, Carpentier PH, Polack B, Pernod G. Quantitative high D-dimer value is predictive of pulmonary embolism occurrence independently of clinical score in a well-defined low risk factor population. J Thromb Haemost 2005;3:93–99.

    Article  PubMed  CAS  Google Scholar 

  50. Bosson JL, Labarere J, Sevestre MA, et al. Deep vein thrombosis in elderly patients hospitalized in sub-acute care facilities. A multicenter cross-sectional study of risk factors, prophylaxis and prevalence. Arch Intern Med 2003;163:2613–2618.

    Article  PubMed  Google Scholar 

  51. 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;109:357–361.

    Article  PubMed  CAS  Google Scholar 

  52. Kovacs MJ, MacKinnon KM, Anderson DR, et al. A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism. Br J Haematol 2001;115:140–144.

    Article  PubMed  CAS  Google Scholar 

  53. 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.

    PubMed  Google Scholar 

  54. Perzanowski C, Dellweg D, Eiger G. Limited use of the SimpliRED assay in confirming pulmonary embolism. Thromb Haemost 2004;91:633–635.

    PubMed  CAS  Google Scholar 

  55. Meyer G, Fischer AM, Collignon MA, et al. Diagnostic value of two rapid and individual D-dimer assays in patients with clinically suspected pulmonary embolism: comparison with microplate enzyme-linked immunosorbent assay. Blood Coagul Fibrinolysis 1998;9:603–608.

    Article  PubMed  CAS  Google Scholar 

  56. de Monye W, Huisman MV, Pattynama PMT. Observer dependency of the Simplired D-Dimer assay in 81 consecutive patients with suspected pulmonary embolism. Thromb Res 1999;96:293–298.

    Article  PubMed  Google Scholar 

  57. Turkstra F, van Beek EJR, Buller HR. Observer and biological variation of a rapid whole blood d-dimer test. Thromb Haemost 1998;79:1–3.

    Google Scholar 

  58. Kraaijenhagen RA, Lijmer JG, Bossuyt PMM, Prins MH, Heisterkamp SH, Buller HR. The accuracy of D-dimer in the diagnosis of venous thromboembolism: a meta-analysis. In: Kraaijenhagen RA, ed. The Etiology, Diagnosis and Treatment of Venous Thromboembolism. Repro Deventer, Deventer, The Netherlands; 2000, pp. 159–183.

    Google Scholar 

  59. Heim SW, Schectman JM, Siadaty MS, Philbrick JT. D-dimer testing for deep venous thrombosis: a metaanalysis. Clin Chem 2004;50:1136–1147.

    Article  PubMed  CAS  Google Scholar 

  60. Henry JW, Relyea B, Stein PD. Continuing risk of thromboemboli among patients with normal pulmonary angiograms. Chest 1995;107:1375–1378.

    PubMed  CAS  Google Scholar 

  61. Hull RD, Raskob GE, Coates G, Panju AA. Clinical validity of a normal perfusion lung scan on patients with suspected pulmonary embolism. Chest 1990;97:23–26.

    Article  PubMed  CAS  Google Scholar 

  62. van Beek EJ, Kuyer PMM, Schenk BE, Brandjes DPM, ten Cate JW, Buller HR. A normal perfusion lung scan in patients with clinically suspected pulmonary embolism: frequency and clinical validity. Chest 1995;108:170–173.

    PubMed  Google Scholar 

  63. Kipper MS, Moser KM, Kortman KE, Ashburn WL. Longterm follow-up of patients with suspected pulmonary embolism and a normal lung scan. Perfusion scans in embolic suspects. Chest 1982;82:411–415.

    Article  PubMed  CAS  Google Scholar 

  64. Gosselin MV, Rubin GD, Leung AN, Huang J, Rizk NW. Unsuspected pulmonary embolism: prospective detection on routine helical CT scans. Radiology 1998;208:209–215.

    PubMed  CAS  Google Scholar 

  65. Storto ML, Di Credico A, Guido F, Larici AR, Bonomo L. Incidental detection of pulmonary emboli on routine MDCT of the chest. AJR Am J Roentgenol 2005;184:264–267.

    PubMed  Google Scholar 

  66. Anderson DR, Kovacs MJ, Dennie C, et al. Use of spiral computerized tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department. (Accepted for publication J Emerg Med 2005;29:399–404.)

    Google Scholar 

  67. Moores LK, Jackson WL Jr, Shorr AF, Jackson JL. Meta-analysis: outcomes in patients with suspected pulmonary embolism managed with computed tomographic pulmonary angiography. Ann Intern Med 2004;141:866–874.

    PubMed  Google Scholar 

  68. Rathbun SW, Raskob G, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med 2000;132:227–232.

    PubMed  CAS  Google Scholar 

  69. Worsley DF, Alavi A. Comprehensive analysis of the results of the PIOPED study. Prospective Investigation of Pulmonary Embolism Diagnosis Study. J Nucl Med 1995;36:2380–2387.

    PubMed  CAS  Google Scholar 

  70. 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;160:293–298.

    Article  PubMed  CAS  Google Scholar 

  71. Cohen J. Statistical Power Analysis for the Behavioural Sciences, 2nd ed. Lawrence Erlbaum Associates: Hillsdale; 1988.

    Google Scholar 

  72. Bayes T. An essay towards solving a problem in the doctrine of chances. Philos Trans R Soc Lon 1763;53:370–418.

    Google Scholar 

  73. Perrier A, Roy P-M, 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.

    Article  PubMed  Google Scholar 

  74. Perrier A, Desmarais S, Miron MJ, et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999;353:190–195.

    Article  PubMed  CAS  Google Scholar 

  75. Goldstein NM, Kollef MH, Ward S, Gage BF. The impact of the introduction of a rapid D-dimer assay on the diagnostic evaluation of suspected pulmonary embolism. Arch Intern Med 2001;161:567–571.

    Article  PubMed  CAS  Google Scholar 

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Wells, P.S. (2007). Clinical Probability and D-Dimer Testing. In: Konstantinides, S.V. (eds) Management of Acute Pulmonary Embolism. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59745-287-8_1

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