Performance of the 4-Level Pulmonary Embolism Clinical Probability Score (4PEPS) in the diagnostic management of pulmonary embolism: An external validation study

Thromb Res. 2023 Nov:231:65-75. doi: 10.1016/j.thromres.2023.09.010. Epub 2023 Sep 20.


Background: The recently published 4-level Pulmonary Embolism Clinical Probability Score (4PEPS) integrates different aspects from currently available diagnostic strategies to further reduce imaging testing in patients with clinically suspected pulmonary embolism (PE).

Aim: To externally validate the performance of 4PEPS in an independent cohort.

Methods: In this post-hoc analysis of the prospective diagnostic management YEARS study, the primary outcome measures were discrimination, calibration, efficiency (proportion of imaging tests potentially avoided), and failure rate (venous thromboembolism (VTE) diagnosis at baseline or follow-up in patients with a negative 4PEPS algorithm). Multiple imputation was used for missing 4PEPS items. Based on 4PEPS, PE was considered ruled out in patients with a very low clinical pre-test probability (CPTP) without D-dimer testing, in patients with a low CPTP and D-dimer <1000 μg/L, and in patients with a moderate CPP and D-dimer below the age-adjusted threshold.

Results: Of the 3465 patients, 474 (14 %) were diagnosed with VTE at baseline or during 3-month follow-up. Discriminatory performance of the 4PEPS items was good (area under ROC-curve, 0.82; 95%CI, 0.80-0.84) as was calibration. Based on 4PEPS, PE could be considered ruled out without imaging in 58 % (95%CI 57-60) of patients (efficiency), for an overall failure rate of 1.3 % (95%CI 0.86-1.9).

Conclusion: In this retrospective external validation, 4PEPS appeared to safely rule out PE with a high efficiency. Nevertheless, although not exceeding the failure rate margin by ISTH standards, the observed failure rate in our analysis appeared to be higher than in the original 4PEPS derivation and validation study. This highlights the importance of a prospective outcome study.

Keywords: D-dimer; Diagnosis; Diagnostic imaging; Pulmonary embolism; Venous thromboembolism.

MeSH terms

  • Fibrin Fibrinogen Degradation Products / analysis
  • Humans
  • Probability
  • Prospective Studies
  • Pulmonary Embolism* / diagnosis
  • Retrospective Studies
  • Venous Thromboembolism* / diagnosis


  • Fibrin Fibrinogen Degradation Products