Production of anti-PF4 antibodies in antiphospholipid antibody-positive patients is not affected by COVID-19 vaccination

  1. Paola Adele Lonati
  2. Caterina Bodio
  3. Mariangela Scavone
  4. Giuliana Martini
  5. Elisa Pesce
  6. Alessandra Bandera
  7. Andrea Lombardi
  8. Maria Gerosa
  9. Franco Franceschini
  10. Angela Tincani
  11. Gianmarco Podda
  12. Sergio Abrignani
  13. Renata Grifantini
  14. Marco Cattaneo
  15. Maria Orietta Borghi
  16. Pier Luigi Meroni

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Abstract

Antibodies against cationic platelet chemokine, platelet factor 4 (PF4/CXCL4), have been described in heparin-induced thrombocytopenia (HIT), but also in patients positive for antiphospholipid antibodies (aPL) even in the absence of heparin treatment and HIT-related clinical manifestations. Anti-PF4 antibodies have been recently described also in subjects who developed thrombosis with thrombocytopenia syndrome (TTS) in association with adenoviral vector-based, but not with mRNA-based, COVID-19 vaccines.

Objective

To investigate whether COVID-19 vaccination affects the production of anti-PF4 antibodies in aPL-positive patients and in control groups.

Methods

Anti-PF4 immunoglobulins were detected in patients’ and controls’ serum samples by ELISA and their ability to activate normal platelets was assessed by the platelet aggregation test.

Results

Anti-PF4 were found in 9 of 126 aPL-positive patients, 4 of 50 patients with COVID-19, 9 of 49 with other infections, and 1 of 50 aPL-negative patients with systemic lupus erythematosus. Clinical manifestations of TTS were not observed in any aPL patient positive for anti-PF4, whose serum failed to cause platelet aggregation. The administration of COVID-19 vaccines did not affect the production of anti-PF4 immunoglobulins or their ability to cause platelet aggregation in 44 aPL-positive patients tested before and after vaccination.

Conclusions

Heparin treatment-independent anti-PF4 antibodies can be found in aPL-positive patients and asymptomatic carriers, but their presence, titre as well as in vitro effect on platelet activation are not affected by COVID-19 vaccination.

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  1. Version published to 10.1136/rmdopen-2021-001902
  2. ScreenIT

    SciScore for 10.1101/2021.08.12.21261976: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The Ethics Committee at Istituto Auxologico Italiano approved the study (08-01-2021).
    Consent: All the patients/subjects gave their informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-PF4 antibodies are detectable in 1.0-4.3% of normal healthy subjects (NHS), depending on the commercial kit used.
    Anti-PF4
    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: 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: 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 10.1101/2021.08.12.21261976v1 on medRxiv