Platelet‐activating immune complexes identified in critically ill COVID‐19 patients suspected of heparin‐induced thrombocytopenia

  1. Ishac Nazy
  2. Stefan D. Jevtic
  3. Jane C. Moore
  4. Angela Huynh
  5. James W. Smith
  6. John G. Kelton
  7. Donald M. Arnold

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Abstract

No abstract available

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  1. Version published to 10.1111/jth.15283
  2. ScreenIT

    SciScore for 10.1101/2020.11.04.20226076: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Hamilton Integrated Research Ethics Board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Testing for anti-PF4/heparin antibodies was done using an anti-PF4/heparin enzymatic immunoassay (EIA, LIFECODES PF4 enhanced assay, Immucor GTI Diagnostics, Waukesha, Wisconsin) for IgG, IgM, and IgA PF4-heparin antibodies.
    anti-PF4/heparin
    suggested: None
    IgA PF4-heparin
    suggested: None
    An anti-human CD32 antibody (IV.3) was added to the SRA to confirm FcγRIIA engagement.12 Testing for IgG-, IgA- and IgM specific antibodies against the RBD and spike protein of SARS-CoV-2 virus was done using our in-house ELISA.
    anti-human CD32
    suggested: None
    IgM
    suggested: None
    ADAMTS13 metalloproteinase activity and anti-ADAMTS13 antibody were tested for all patients, as previously described, to determine whether VWF changes were related to ADAMTS13 activity.
    ADAMTS13
    suggested: None

    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:
    A limitation of this study is the inability to characterize the specificity of these platelet-activating ICs. It is possible that the ICs are composed of COVID-19 virus-antibody complexes, as seen with H1N1 viral infection.21 This is further supported by inhibition with therapeutic heparin, since heparin binds the SARS-CoV-2 RBD to cause a conformational change with altered binding specificity, potentially disrupting the ICs and inhibiting platelet activation.22 Regardless, the data presented here clearly outline the characteristics of these ICs and differentiate them from other severe coagulation disorders, including HIT and TTP. We thus propose a model whereby certain severe CAC patients feature a novel IC-mediated thrombotic microangiopathy that is characterized by significant platelet and endothelial cell activation. These ICs can produce a highly prothrombotic state resembling HIT but with unique platelet activating properties.

    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 10.1101/2020.11.04.20226076v1 on medRxiv