Elevated d-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019

  1. Siddharth Shah
  2. Kuldeep Shah
  3. Siddharth B. Patel
  4. Foram S. Patel
  5. Mohammed Osman
  6. Poonam Velagapudi
  7. Mohit K. Turagam
  8. Dhanunjaya Lakkireddy
  9. Jalaj Garg

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Abstract

The 2019 novel coronavirus, declared a pandemic, has infected 2.6 million people as of April 27, 2020, and has resulted in the death of 181,938 people. d -dimer is an important prognostic tool, is often elevated in patients with severe coronavirus disease-19 (COVID-19) infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of d -dimer in COVID-19-infected patients. We searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission d -dimer levels in COVID-19 patients and its effect on mortality. Eighteen studies (16 retrospective and 2 prospective) with a total of 3682 patients met the inclusion criteria. The pooled weighted mean difference (WMD) demonstrated significantly elevated d -dimer levels in patients who died versus those who survived (WMD, 6.13 mg/L; 95% confidence interval [CI] 4.16–8.11; P < 0.001). Similarly, the pooled mean d -dimer levels were significantly elevated in patients with severe COVID-19 infection (WMD, 0.54 mg/L; 95% CI 0.28–0.80; P < 0.001). The risk of mortality was fourfold higher in patients with positive d -dimer versus negative d -dimer (risk ratio, 4.11; 95% CI, 2.48–6.84; P < 0.001) and the risk of developing severe disease was twofold higher in patients with positive d -dimer levels versus negative d -dimer (risk ratio, 2.04; 95% CI, 1.34–3.11; P < 0.001). Our meta-analysis demonstrates that patients with COVID-19 infection presenting with elevated d -dimer levels have an increased risk of severe disease and mortality.

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  1. Version published to 10.1097/crd.0000000000000330
  2. ScreenIT

    SciScore for 10.1101/2020.04.29.20085407: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We performed a systematic search, without language restriction, using PubMed, EMBASE, SCOPUS, Google Scholar, and two preprint servers (https://www.medrxiv.org/ and https://www.ssrn.com/index.cfm/en/coronavirus/) from inception to April 16th, 2020, for studies that reported D-dimer levels in COVID-19 patients.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    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: We detected the following sentences addressing limitations in the study:
    Our study has a few important limitations. First, all studies included in our meta-analysis were from China, while the United States and Europe have the majority of COVID-19 cases currently. However, the preliminary reports from the United States and Europe have shown similar trends in COVID-19 infection in terms of clinical presentation and outcomes 5, 49. Our pooled analysis provides the best available data regarding trends of D-dimer levels in patients with COVID-19 infection and the likelihood of developing severe infection or mortality in patients with elevated D-dimer levels. Secondly, all studies included in our analysis were either prospective or retrospective reports, which is currently the best available evidence; and, therefore, subject to potential confounding and publication bias. Third, significant heterogeneity was observed between studies in our pooled analysis. Fourth, details on anticoagulation or trends of D-dimer over the course of hospitalization were not available. Finally, patient-level data to perform additional. detailed analyses are not available.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    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.

  3. Version published to 10.1101/2020.04.29.20085407v1 on medRxiv