Diagnostic accuracy of age-adjusted D-dimer for pulmonary embolism among Emergency Department patients with suspected SARS-COV-2: A Canadian COVID-19 Emergency Department Rapid Response Network study

  1. K Lin
  2. K Xu
  3. R Daoust
  4. J Taylor
  5. R Rosychuk
  6. JP Hau
  7. P Davis
  8. G Clark
  9. A McRae
  10. CM Hohl

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Abstract

Importance

Ruling out pulmonary embolism (PE) among patients presenting to the Emergency Department (ED) with suspected or confirmed SARS-COV-2 is challenging due to symptom overlap, known increased pro-thrombotic risk, and unclear D-dimer test interpretation.

Objective

Our primary objective was to assess the diagnostic accuracy of standard and age-adjusted D-dimer test thresholds for predicting 30-day pulmonary embolism (PE) diagnosis in patients with suspected SARS-COV-2 infection.

Design, Setting, and Participants

This was a retrospective observational study using data from 50 sites enrolling patients into the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry between March 1, 2020 to July 2, 2021. Adults ( ≥ 18 years) with SARS-COV-2 testing performed at index ED visit were included if they had any of the following presenting complaints: chest pain, shortness of breath, hypoxia, syncope/presyncope, or hemoptysis. We excluded patients with duplicate records or no valid provincial healthcare number.

Main Outcomes and Measures

Our primary end point was 30-day PE diagnosis based on a positive computed tomography pulmonary angiogram (CTPA) or hospital discharge diagnosis code of PE. The outcome measure was the diagnostic accuracy of an age adjusted D-dimer strategy as compared to absolute D-dimer thresholds (500 – 5000 ng/mL).

Results

52,038 patients met inclusion criteria. Age-adjusted D-dimer had a sensitivity (SN) of 96% (95% CI 93-98%) and a specificity (SP) of 48% (95% CI 48-49%) which was comparable to the most sensitive absolute threshold of 500 ng/mL (SN 98%, 95% CI 96-99%; SP 41%, 95% CI 40-42%). Other absolute D-dimer thresholds did not perform well enough for clinical reliability (SN <90%). Both age-adjusted and absolute D-dimer performed better in SARS-COV-2 negative patients as compared to SARS-COV-2 positive patients for predicting 30-day PE diagnosis (c-statistic 0.88 vs 0.80).

Conclusions and Relevance

In this large Canadian cohort of ED patients with suspected SARS-COV-2 infection, an age-adjusted D-dimer strategy had similar sensitivity and superior specificity to the most sensitive D-dimer threshold of 500 ng/mL for predicting 30-day PE diagnosis irrespective of SARS-COV-2 infection status. Adopting an age-adjusted D-dimer strategy in patients with suspected SARS-COV-2 may help avoid unnecessary CTPA testing without compromising safety.

Trial Registration

Clinicaltrials.gov , NCT04702945

KEY POINTS

Question

What is the diagnostic accuracy of age-adjusted and absolute D-dimer thresholds for investigating PE in ED patients with suspected SARS-COV-2?

Findings

An age-adjusted D-dimer strategy had comparable sensitivity and higher specificity for 30-day PE diagnosis compared to the most sensitive absolute threshold of 500 ng/mL irrespective of patient’s SARS-COV-2 status.

Meaning

Consider using an age-adjusted D-dimer threshold for PE risk stratification in ED patients with suspected SARS-COV-2.

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  1. ScreenIT

    SciScore for 10.1101/2022.03.07.22272036: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The ethics review boards of all participating sites reviewed and approved the study with a waiver for informed consent for study enrolment.
    Consent: The ethics review boards of all participating sites reviewed and approved the study with a waiver for informed consent for study enrolment.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingResearch assistants were blinded to the objectives of this analysis.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04702945RecruitingCanadian COVID-19 Emergency Department Registry

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2022.03.07.22272036v1 on medRxiv