Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study

Aniek F Markus; Victoria Y Strauss; Edward Burn; Xintong Li; Antonella Delmestri; Christian Reich; Can Yin; Miguel A Mayer; Juan-Manuel Ramírez-Anguita; Edelmira Marti; Katia M C Verhamme; Peter R Rijnbeek; Daniel Prieto-Alhambra; Annika M Jödicke

doi:10.3389/fphar.2023.1118203

Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study

Front Pharmacol. 2023 Mar 24:14:1118203. doi: 10.3389/fphar.2023.1118203. eCollection 2023.

Authors

Aniek F Markus¹, Victoria Y Strauss², Edward Burn^{2

3}, Xintong Li², Antonella Delmestri¹, Christian Reich⁴, Can Yin⁴, Miguel A Mayer⁵, Juan-Manuel Ramírez-Anguita⁵, Edelmira Marti⁶, Katia M C Verhamme^{1

7}, Peter R Rijnbeek¹, Daniel Prieto-Alhambra^{1

2}, Annika M Jödicke²

Affiliations

¹ Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands.
² Centre for Statistics in Medicine (CSM), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDROMS), University of Oxford, Oxford, United Kingdom.
³ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
⁴ Real World Solutions, IQVIA, Durham, NC, United States.
⁵ Hospital del Mar Medical Research Institute (IMIM), Universitat Pompeu Fabra, Parc de Salut Mar, Barcelona, Spain.
⁶ Hematology Department. Hospital Clínico Universitario de Valencia, Valencia, Spain.
⁷ Department of Bioanalysis, Ghent University, Ghent, Belgium.

Abstract

Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.

Keywords: COVID-19; anticoagulation; drug utilization; epidemiology; thromboembolic events; treatment pathways; vaccination.

Grants and funding

This study was funded under the specific contract FWC EMA/2017/09/PE Lot 3 between Erasmus MC and the European Medicines Agency (EMA). This manuscript expresses the opinion of the authors of the paper, and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties. DPA received partial support from the National Institute for Health and Care Research (NIHR) in the form of a Senior Research Fellowship and the Oxford NIHR Biomedical Research Centre (BRC).