Coronavirus-19 and coagulopathy: A Systematic Review [COVID-COAG]

  1. Stephanie G Lee
  2. Michael Fralick
  3. Grace Tang
  4. Brandon Tse
  5. Lisa Baumann Kreuziger
  6. Mary Cushman
  7. Peter Juni
  8. Michelle Sholzberg

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Abstract

Background

Understanding the association between Coronavirus Disease 2019 (COVID-19) and coagulopathy may assist clinical prognostication, and influence treatment and outcomes. We aimed to systematically describe the relationship between hemostatic laboratory parameters and important clinical outcomes among adults with COVID-19.

Methods

A systematic review of randomized clinical trials, observational studies and case series published in PubMed (Medline), EMBASE, and CENTRAL from December 1, 2019 to March 25, 2020. Studies of adult patients with COVID-19 that reported at least one hemostatic laboratory parameter were included.

Results

Data were extracted from 57 studies (N=12,050 patients) that met inclusion criteria. The average age of patients was 52 years and 45% were women. Of the included studies, 92.7% (N=38/41 studies) reported an average platelet count ≥ 150 × 10 9 /L, 68.2% (N=15/22 studies) reported an average prothrombin time (PT) between 11-14 s, 55% (N=11/20 studies) reported an average activated partial thromboplastin time (aPTT) between 25-35 s, and 34.4% (N=11/32 studies) reported a D-dimer concentration above the upper limit of normal (ULN). Eight studies (7 cohorts and 1 case series) reported hemostatic lab values for survivors versus non-survivors. Among non-survivors, D-dimer concentrations were reported in 4 studies and all reported an average above the ULN.

Interpretation

Most patients had a normal platelet count, elevated D-dimer, PT and aPTT values in the upper reference interval; D-dimer elevation appeared to correlate with poor outcomes. Further studies are needed to better correlate these hemostatic parameters with the risk of adverse outcomes such as thrombosis and bleeding.

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  1. Version published to 10.1101/2021.01.05.20248202v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.01.05.20248202: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationWe included randomized control trials, observational studies, and case series that had at least 3 study participants.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search Strategy: PubMed (MEDLINE), EMBASE, and CENTRAL were searched from December 1, 2019 until March 25, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    To supplement this, Google Scholar was searched to capture grey literature and the first 100 titles were screened for eligibility.
    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:
    There are a number of important limitations to our study. First, most of the included patients were from China and thus the rates of thromboembolism might be underestimated as Asian ethnicity appears to be associated with a lower risk of thromboembolism(19). Second, most included studies did not quantify the association between abnormal coagulation parameters and the risk of adverse events (e.g., respiratory failure, mortality) and those that did generally lacked external validation. Third, there was high variability in the type of D-dimer assay used across studies, which made it inappropriate to meta-analyze results. Fourth, we only studied hospitalized adult patients, so it is unknown how results apply to children or other patient populations such as ambulatory patients or pregnant women. Necessary future directions include antithrombotic clinical trials in the pre-hospital, pre-intensive care, intensive care, and post-hospital care settings. Clinical trial emphasis on speed and pragmatism is required given the immediate clinical need and risk of loss of equipoise. Furthermore, prediction models are needed to understand which hemostatic laboratory parameters, or combination thereof, portend the highest risk for adverse outcomes. Our summarized data provide a systematic review of the literature describing COVID-19 associated coagulopathy, the thrombo-inflammatory pattern of COVID-19 associated coagulopathy, and its association with poor clinical outcomes. This information wi...

    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 10.1101/2021.01.05.20248202v1 on medRxiv