Pulmonary embolism diagnosis and the D-dilemma (2025)

1. http://orcid.org/0000-0002-0400-2017Daniel Horner1,2,
2. Lara N Roberts3,4

1. ¹Emergency Department, Northern Care Alliance NHS Foundation Trust, Salford, UK
2. ²Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Manchester, UK
3. ³King’s Thrombosis Centre, Department of Haematological Medicine, King’s College Hospital NHS Foundation Trust, London, UK
4. ⁴King’s College London, London, England, UK

1. Correspondence to Professor Daniel Horner; daniel.horner{at}nca.nhs.uk

• thrombo-embolic disease
• pulmonary embolism
• Diagnostic Tests

The D-dimer is a stable termination product of fibrin degradation. It was introduced as a biomarker of coagulation activation in the early 1970s and first evaluated as a test to exclude venous thromboembolism (VTE) in the 1980s.1 It has since been widely adopted into diagnostic care pathways across the world, despite well-documented issues with variation across laboratory assays and reporting units.2 D-dimer is often viewed as a dichotomous test (positive or negative) based on the standard threshold of 500 ng/mL fibrinogen equivalent units (FEUs) used in original derivation studies, despite being a continuous variable.3 Like so many tests in medicine, there is potential for more effective use.

Several research groups have worked to this end and evaluated the potential impact of adjusting the D-dimer threshold according to age, clinical pre-test probability or gestalt. This approach has clear merit; the specificity of the test is low at the standard threshold (500 ng/mL FEU); continuous/ordinal biomarkers in other clinical models have been shown to enhance risk prediction4; and patients and clinicians have different levels of risk tolerance. In their EMJ paper, Morris et al5 present a feasibility study evaluating the ‘adjust unlikely’ rule for exclusion of pulmonary embolism (PE) in the ED. This rule asks the treating clinician to determine whether they believe PE to be the most likely diagnosis, using only gestalt. PE can be excluded if it is not considered the most likely diagnosis and the D-dimer value is below an age-adjusted threshold. If PE is considered most likely, a standard threshold is …

Footnotes

• Handling editor Richard Body

• X @Exrcemprof

• Contributors DH conceived the article and prepared the first draft. LNR critically revised the manuscript and provided ongoing support and engagement during the peer review process. DH acts as a guarantor.

• Funding No funding was received for work directly relating to this article. DH is the current recipient of a Senior Clinical Practitioner and Researcher Award (NIHR 304434) which funds a proportion of time for academic work.

• Competing interests DH acted as a topic expert for the 2020 NICE guideline on venous thromboembolic disease and is a co-investigator for the recently funded RCEM study on diagnostic algorithms for VTE assessment. DH and LNR are current topic experts for a guideline in production from the British Society of Haematology titled ‘A British Society for Haematology Guideline on laboratory and clinical aspects of D dimer testing’. LNR has previously received speaker fees from Bayer and Viatris.

• Provenance and peer review Commissioned; internally peer reviewed.

• Original research

  Adjust-Unlikely pulmonary embolism testing using telephone recruitment: a pilot study to assess the feasibility of evaluating its safety and efficiency

  Nicole F MorrisRasha GeorgieChristine L D’ArsignyPaula JamesSameer ParpiaFederico GerminiNatasha ClaytonDavid GoodKerstin de Wit

  Emergency Medicine Journal 2025; - Published Online First: 13 May 2025. doi: 10.1136/emermed-2024-214465