Download PDF
Thromb Haemost 2017; 117(08): 1622-1629
DOI: 10.1160/TH17-02-0076
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Is a normal computed tomography pulmonary angiography safe to rule out acute pulmonary embolism in patients with a likely clinical probability?

A patient-level meta-analysis
Tom van der Hulle
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
,
Nick van Es
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Paul L. den Exter
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
,
Josien van Es
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Inge C. M. Mos
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
,
Renée A. Douma
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Marieke J. H. A. Kruip
3   Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands
,
Marcel M. C. Hovens
4   Department of Internal Medicine, Rijnstate Hospital, Arnhem, the Netherlands
,
Marije ten Wolde
5   Department of Internal Medicine, Flevoziekenhuis Hospital, Almere, the Netherlands
,
Mathilde Nijkeuter
6   Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
,
Hugo ten Cate
7   Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands
8   Department of Internal Medicine and Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands
,
Pieter W. Kamphuisen
9   Department of Vascular Medicine, University Medical Center Groningen, Groningen, the Netherlands
,
Harry R. Büller
2   Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands
,
Menno V. Huisman
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
,
Frederikus A. Klok
1   Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
› Author Affiliations
Further Information

Publication History

Received: 02 February 2017

Accepted after major revision: 20 April 2017

Publication Date:
22 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

A normal computed tomography pulmonary angiography (CTPA) remains a controversial criterion for ruling out acute pulmonary embolism (PE) in patients with a likely clinical probability. We set out to determine the risk of VTE and fatal PE after a normal CTPA in this patient category and compare these risk to those after a normal pulmonary angiogram of 1.7% (95%CI 1.0–2.7%) and 0.3% (95%CI 0.02–0.7%). A patient-level meta-analysis from 4 prospective diagnostic management studies that sequentially applied the Wells rule, D-dimer tests and CTPA to consecutive patients with clinically suspected acute PE. The primary outcome was the 3-month VTE incidence after a normal CTPA. A total of 6,148 patients were included with an overall PE prevalence of 24%. The 3-month VTE incidence in all 4,421 patients in whom PE was excluded at baseline was 1.2% (95%CI 0.48–2.6) and the risk of fatal PE was 0.11% (95%CI 0.02–0.70). In patients with a likely clinical probability the 3-month incidences of VTE and fatal PE were 2.0% (95%CI 1.0–4.1%) and 0.48% (95%CI 0.20–1.1%) after a normal CTPA. The 3-month incidence of VTE was 6.3% (95%CI 3.0–12) in patients with a Wells rule >6 points. In conclusion, this study suggests that a normal CTPA may be considered as a valid diagnostic criterion to rule out PE in the majority of patients with a likely clinical probability, although the risk of VTE is higher in subgroups such as patients with a Wells rule >6 points for which a closer follow-up should be considered.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Pulmonary embolism - computed tomography - diagnosis - safety

 

  • References

  • 1 van Belle A, Buller HR, Huisman MV. et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. J Am Med Assoc 2006; 295: 172-179.
    CrossrefPubMedSearch in Google Scholar
  • 2 Douma RA, Mos IC, Erkens PM. 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: 709-718.
    CrossrefPubMedSearch in Google Scholar
  • 3 Righini M, Van Es J, Den Exter PL. et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. J Am Med Assoc 2014; 311: 1117-1124.
    CrossrefPubMedSearch in Google Scholar
  • 4 Mos IC, Klok FA, Kroft LJ. et al. 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. J Thromb Haemost 2009; 07: 1491-1498.
    CrossrefPubMedSearch in Google Scholar
  • 5 Huisman MV, Klok FA. Diagnostic management of acute deep vein thrombosis and pulmonary embolism. J Thromb Haemost 2013; 11: 412-422.
    CrossrefPubMedSearch in Google Scholar
  • 6 Kooiman J, Klok FA, Mos IC. et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost 2010; 08: 409-411.
    CrossrefPubMedSearch in Google Scholar
  • 7 Sarma A, Heilbrun ME, Conner KE. et al. Radiation and chest CT scan examinations: what do we know?. Chest 2012; 142: 750-760.
    CrossrefPubMedSearch in Google Scholar
  • 8 Konstantinides SV, Torbicki A, Agnelli G. et al. 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35: 3033-3069k.
    CrossrefPubMedSearch in Google Scholar
  • 9 Douma RA, Le Gal G, Sohne M. et al. Potential of an age adjusted D-dimer cutoff value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. Br Med J 2010; 340: c1475.
    CrossrefPubMedSearch in Google Scholar
  • 10 van der Hulle T, Dronkers CE, Klok FA. et al. Recent developments in the diagnosis and treatment of pulmonary embolism. J Intern Med 2015; 279: 16-29.
    PubMedSearch in Google Scholar
  • 11 Pasha SM, Klok FA, Snoep JD. et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res 2010; 125: e123-e127.
    CrossrefPubMedSearch in 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.
    CrossrefPubMedSearch in Google Scholar
  • 13 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.
    CrossrefPubMedSearch in Google Scholar
  • 14 Righini M, Le Gal G, Aujesky D. et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet 2008; 371: 1343-1352.
    CrossrefPubMedSearch in Google Scholar
  • 15 Mos IC, Douma RA, Erkens PM. et al. Diagnostic outcome management study in patients with clinically suspected recurrent acute pulmonary embolism with a structured algorithm. Thromb Res 2014; 133: 1039-1044.
    CrossrefPubMedSearch in Google Scholar
  • 16 Douma RA, Kamphuisen PW, Huisman MV. et al. False normal results on multidetector-row spiral computed tomography in patients with high clinical probability of pulmonary embolism. J Thromb Haemost 2008; 06: 1978-1979.
    CrossrefPubMedSearch in Google Scholar
  • 17 Bates SM, Jaeschke R, Stevens SM. et al. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e351S-e418S.
    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: 416-420.
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Rubin DB. Inference and Missing Data. Biometrika 1976; 63: 581-592.
    CrossrefPubMedSearch in Google Scholar
  • 20 van Beek EJ, Brouwerst EM, Song B. et al. Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism--a critical review. Clin Radiol 2001; 56: 838-842.
    CrossrefPubMedSearch in Google Scholar
  • 21 Dronkers CE, van der Hulle T, Le Gal G. et al. Subcommittee on Predictive and Diagnostic Variables in Thrombotic Disease. Towards a tailored diagnostic standard for future diagnostic studies in pulmonary embolism: communication from the SSC of the ISTH. J Thromb Haemost. 2017 Epub ahead of print.
    PubMedSearch in Google Scholar
  • 22 Heit JA, Silverstein MD, Mohr DN. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815.
    CrossrefPubMedSearch in Google Scholar
  • 23 Blom JW, Doggen CJ, Osanto S. et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. J Am Med Assoc 2005; 293: 715-722.
    CrossrefPubMedSearch in Google Scholar
  • 24 Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012; 09: e1001275.
    CrossrefPubMedSearch in Google Scholar
  • 25 Stein PD, Fowler SE, Goodman LR. et al. Multidetector computed tomography for acute pulmonary embolism. N Eng J Med 2006; 354: 2317-2327.
    CrossrefPubMedSearch in Google Scholar
  • 26 Moores L, Kline J, Portillo AK. et al. Multidetector computed tomographic pulmonary angiography in patients with a high clinical probability of pulmonary embolism. J Thromb Haemost 2016; 14: 114-120.
    CrossrefPubMedSearch in Google Scholar