Vaccines against Covid-19, venous thromboembolism, and thrombocytopenia. A population-based retrospective cohort study

  1. Joan-Ramon Laporte
  2. Ermengol Coma
  3. Francesc Fina
  4. Luís García-Eroles
  5. Xavier Vidal
  6. Manuel Medina

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Abstract

Background

We aimed at estimating the risk of venous thromboembolism (VTE), thrombocytopenia (TCP), and VTE associated with TCP, by age and sex, after the first dose of both adenovirus vector-based and mRNA-based Covid-19 vaccines, and after the second dose of m-RNA vaccines.

Methods

In this population-based retrospective cohort study in the national health care databases in Catalonia, we examined three groups: 1 662 719 people 10 years of age and over vaccinated with the first dose of a Covid-19 vaccine, 622 778 with the second dose, and 190 616 diagnosed of Covid-19 in the same period (between1 January 2021 and 18 April 2021). The rates of various clinical presentations of VTE and TCP were compared with those in the reference population (7 013 040 people served by the health care system in 2019). The two primary outcomes were the observed 21 day rate of a composite variable of cerebral venous sinus thrombosis, mesenteric thrombosis, portal vein thrombosis, or any venous thromboembolism (VTE) associated with thrombocytopenia (TCP), and the rate of any VTE associated with TCP (VTE+TCP). Analyses were standardised by age and sex.

Results

The 21 day rate per 100 000 of the primary composite variable was 2.15 in the reference population, 5.65 following the first vaccine dose (standardised difference, 2.53 (95% CI [CI], 1.04 to 4.00), and 7.23 following the second dose (standardised difference, 4.07 (95% CI, 1.43 to 6.70). The event rates of VTE+TCP and of all the secondary variables showed the same patterns.

Excess event rates were higher in men than in women, and they were not especially increased in any particular age group. All Covid-19 vaccines were associated with increased rates of the outcome variables.

Excess event rates were much higher in the Covid-19 cohort (35.60 per 100 000 (95% CI, 26.15 to 45.06).

Conclusions

We observed increases of rates of venous thromboembolism in usual and unusual anatomical sites and of thrombocytopenia in recipients of both adenovirus vector and mRNA vaccines against Covid-19. Excess rates were higher in men than in women and they were not particularly elevated in any specific age group.

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  1. Version published to 10.1101/2021.07.23.21261036v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.07.23.21261036: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Vaccination with VaxZevria® was temporarily halted between 16 and 22 March.
    VaxZevria®
    suggested: None
    All analyses were performed with SAS® 9.4 (SAS Institute Inc., Cary, NC, USA).
    SAS®
    suggested: (SASqPCR, RRID:SCR_003056)
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    Strengths and weaknesses of this study: Our study has several strengths. First, it was population-based and all potentially vaccinated age groups were included. This allowed the analysis of rates by age groups. Second, we compared the incidence of the outcomes of interest in vaccinated people with the background incidence, and we also examined a contemporary Covid-19 cohort originated from the same population and in the same dataset. This avoids potential systematic error and confounding caused by heterogeneity between healthcare databases.20 Third, we examined the excess rates of various diagnostic definitions of usual and unusual site venous thromboembolism, with or without thrombocytopenia. This allows the analysis of the rates of specific clinical outcomes, and at the same time it gives an overview of the epidemiology of venous thromboembolism in people with Covid-19 and following vaccination. Fourth, rather than examining the risks associated to a particular vaccine, we included all Covid-19 vaccines in use in our country. The yearly incidence rates of the outcome variables in the reference population and the case-fatality rates were similar to those found in other recent studies.21-24 Our findings should however be interpreted in the context of their limitations. First, we did not review the clinical records and haematological data of patients with venous thromboembolism or thrombocytopenia, and therefore we were not able to evaluate laboratory and clinical data which c...

    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.

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  3. Version published to 10.1101/2021.07.23.21261036v1 on medRxiv