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Thromb Haemost 2003; 90(06): 1198-1203
DOI: 10.1160/TH03-03-0175
New Technologies and Diagnostic Tools
Schattauer GmbH

Exclusion of pulmonary embolism using C-reactive protein and D-dimer

A prospective comparison
Drahomir Aujesky
1   Department of Medicine, University Hospital of Lausanne, Switzerland
,
Daniel Hayoz
2   Division of Angiology, University Hospital of Lausanne, Switzerland
,
Bertrand Yersin
3   Department of Emergency Medicine, University Hospital of Lausanne, Switzerland
,
Arnaud Perrier
4   Department of Medicine, University Hospital of Geneva, Switzerland
,
Ghassan Barghouth
5   Department of Radiology, University Hospital of Lausanne, Switzerland
,
Pierre Schnyder
5   Department of Radiology, University Hospital of Lausanne, Switzerland
,
Angelika Bischof-Delaloye
6   Department of Nuclear Medicine, University Hospital of Lausanne, Switzerland
,
Jacques Cornuz
7   Department of Medicine and Institute of Social and Preventive Medicine, University Hospital of Lausanne, Switzerland
› Author Affiliations
Further Information

Publication History

Received 23 March 2003

Accepted after resubmission 27 August 2003

Publication Date:
05 December 2017 (online)

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Summary

Our goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone or combined with clinical probability assessment in patients with suspected pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We conducted a prospective study in which we performed a common immuno-turbidimetric CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in 259 consecutive outpatients with suspected PE at the emergency department of a teaching hospital. We assessed clinical probability of PE by a validated prediction rule overridden by clinical judgment. Patients with D-dimer levels ≥ 500 µg/l underwent a work-up consisting of lower-limb venous ultrasound, spiral computer-ized tomography, ventilation-perfusion scan, or pulmonary angiography. Patients were followed up for three months. Seventy-seven (30%) of the patients had PE.The CRP alone had a sensitivity of 84% (95% confidence interval [CI).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% CI: 78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE (9%) in this subgroup, the NPV increased to 97% (95% CI: 89 to 100%). The D-dimer (cutpoint 500 µg/l) showed a sensitivity of 100% (95% CI: 95 to 100%) and a NPV of 100% (95% CI: 94 to 100%) irrespective of clinical probability and accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined with clinical probability assessment cannot safely exclude PE.

Keywords

Pulmonary embolism - C-reactive protein - D-dimer - clinical probability assessment
 

  • References

  • 1 Bounameaux H, Cirafici P, de Moerloose P. et al. Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism. Lancet 1991; 337 8736 196-200.
    CrossrefPubMedSearch in Google Scholar
  • 2 Brown MD, Rowe BH, Reeves MJ. et al. The accuracy of the enzyme-linked immunosor-bent assay D-dimer test in the diagnosis of pulmonary embolism: a meta-analysis. Ann Emerg Med 2002; 40 (02) 133-44.
    CrossrefPubMedSearch in Google Scholar
  • 3 Kelly J, Rudd A, Lewis RR. et al. Plasma D-dimers in the diagnosis of venous thromboembolism. Arch Intern Med 2002; 162 (07) 747-56.
    CrossrefPubMedSearch in Google Scholar
  • 4 Perrier A, Desmarais S, Miron MJ. et al. Noninvasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353 9148 190-5.
    CrossrefPubMedSearch in Google Scholar
  • 5 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 (05) 357-61.
    CrossrefPubMedSearch in Google Scholar
  • 6 Wells PS, Anderson DR, Rodger M. 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 (02) 98-107.
    CrossrefPubMedSearch in Google Scholar
  • 7 Maskell NA, Butland RJ. A normal serum CRP measurement does not exclude deep vein thrombosis. Thromb Haemost 2001; 86 (06) 1582-3.
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Thomas EA, Cobby MJ, Rhys Davies E. et al. Liquid crystal thermography and C reactive protein in the detection of deep venous thrombosis. BMJ 1989; 299 6705 951-2.
    CrossrefPubMedSearch in Google Scholar
  • 9 Syrjala H, Haukipuro K, Kiviniemi H. Acute phase response and deep lower limb venous thrombosis. J Clin Pathol 1990; 43 (06) 519-20.
    PubMedSearch in Google Scholar
  • 10 Jossang B, Runde I. Diagnostic value of C-reactive protein and D-dimer in deep venous thrombosis. Tidsskr Nor Laegeforen 1992; 112 (09) 1153-5.
    PubMedSearch in Google Scholar
  • 11 Cooper TJ, Prothero DL, Gillett MG. et al. Laboratory investigation in the diagnosis of pulmonary thromboembolism. Q J Med 1992; 83 (301) 369-79.
    PubMedSearch in Google Scholar
  • 12 Franco JA, Gonzalez-Mangers E, Butler TT. Negative predictive value of C-reactive protein testing. J Nucl Med 1994; 35 (01) 189-90.
    PubMedSearch in Google Scholar
  • 13 Wong NA, Laitt RD, Goddard PR. et al. Serum C reactive protein does not reliably exclude lower limb deep venous thrombosis. Thromb Haemost 1996; 76 (05) 816-7.
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Horney E, Lagerstedt C. Evaluation of analyses for exclusion of suspected thrombosis. Do not rely on the D-dimer test!. Lakartidningen 1997; 94 (50) 4777-9.
    PubMedSearch in Google Scholar
  • 15 Bucek RA, Reiter M, Quehenberger P. et al. C-reactive protein in the diagnosis of deep vein thrombosis. Br J Haematol 2002; 119 (02) 385-9.
    CrossrefPubMedSearch in Google Scholar
  • 16 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 (01) 92-7.
    CrossrefPubMedSearch in Google Scholar
  • 17 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 (04) 269.
    CrossrefPubMedSearch in Google Scholar
  • 18 Wells PS, Anderson DR, Rodger 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 (03) 416-20.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Kearon C, Julian JA, Newman TE. et al. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med 1998; 128 (08) 663-77.
    CrossrefPubMedSearch in Google Scholar
  • 20 Perrier A, Howarth N, Didier D. et al. Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism. Ann Intern Med 2001; 135 (02) 88-97.
    CrossrefPubMedSearch in Google Scholar
  • 21 Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990; 263 (20) 2753-9.
    CrossrefPubMedSearch in Google Scholar
  • 22 Wolfe TR, Hartsell SC. Pulmonary embolism: making sense of the diagnostic evaluation. Ann Emerg Med 2001; 37 (05) 504-14.
    CrossrefPubMedSearch in Google Scholar
  • 23 Bridge PD, Sawilowsky SS. Increasing physicians’ awareness of the impact of statistics on research outcomes: comparative power of the t-test and and Wilcoxon Rank-Sum test in small samples applied research. J Clin Epidemiol 1999; 52 (03) 229-35.
    CrossrefPubMedSearch in Google Scholar
  • 24 Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143 (01) 29-36.
    CrossrefPubMedSearch in Google Scholar
  • 25 Roberts WL, Moulton L, Law TC. et al. Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2. Clin Chem 2001; 47 (03) 418-25.
    PubMedSearch in Google Scholar
  • 26 Kovacs MJ, MacKinnon KM, Anderson D. et al. A comparison of three rapid D-dimer methods for the diagnosis of venous thromboembolism. Br J Haematol 2001; 115 (01) 140-4.
    CrossrefPubMedSearch in Google Scholar