Antiplatelet drugs block platelet activation by VITT patient serum

  1. Christopher W. Smith
  2. Samantha J. Montague
  3. Caroline Kardeby
  4. Ying Di
  5. Gillian C. Lowe
  6. William A. Lester
  7. Steve P. Watson
  8. Phillip L. R. Nicolson

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Abstract

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  1. Version published to 10.1182/blood.2021012277
  2. ScreenIT

    SciScore for 10.1101/2021.04.24.21255655: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Collection of blood from these patients (including those lacking capacity) was approved under research ethics granted to the University of Birmingham Human Biomaterial Resource Centre (North West – Haydock Research Ethics Committee, reference: 15/NW/0079, amendment 3, 19/11/2018).
    IRB: Collection of blood from these patients (including those lacking capacity) was approved under research ethics granted to the University of Birmingham Human Biomaterial Resource Centre (North West – Haydock Research Ethics Committee, reference: 15/NW/0079, amendment 3, 19/11/2018).
    IACUC: Ethical approval for collecting blood from healthy volunteers was granted by Birmingham University Internal Ethical Review Committee (reference: ERN_11-0175, assessed 22/3/2021)
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibodies and reagents: Mouse monoclonal IgG2b antibody against human CD32 (IV.3) was purified from hybridoma cells supernatant, and IV.3 F(ab) fragment made using Pierce Fab Preparation kit (Thermo Fisher Scientific)
    human CD32
    suggested: None
    Software and Algorithms
    SentencesResources
    Rilzabrutinib was provided by Principia BioPharma.
    BioPharma
    suggested: (TransCelerate BioPharma, RRID:SCR_003728)
    Statistical analysis was performed in GraphPad Prism 9 (GraphPad Software Inc.) using one or two-way ANOVA with Dunnett corrections for multiple comparisons.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Limitations of this study are the small sample size, and the difference in treatment patients received prior to sample collection. Additionally, due to the limited amount of sera available and the inter-donor variability of platelet responsiveness to serum, only a limited number of conditions could be tested. In conclusion, serum from patients with VITT activates platelets via FcγRIIA, which can be blocked in vitro by anti-platelet therapies and downstream kinase inhibitors. This suggests that prophylaxis in at risk groups with commonly used anti-platelet agents such as aspirin may potentially be able to reduce the impact of VITT and that tyrosine kinase inhibitors may be a treatment for clinically manifest VITT in addition to the current management intervention with corticosteroids and IVIg. These strategies, however, require further study.

    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.

    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.

  3. Version published to 10.1101/2021.04.24.21255655v1 on medRxiv