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CC BY 4.0 · Thromb Haemost
DOI: 10.1055/a-2665-2400
Stroke, Systemic or Venous Thromboembolism

Venous Thrombosis Associated with Different Types of SARS-CoV-2 Vaccines in the Netherlands—Results of the TERA Case-Control Study

Willian J. van Dijk 
1   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Agnes C. Kant 
2   The Netherlands Pharmacovigilance Centre Lareb, 's-Hertogenbosch, The Netherlands
,
Astrid van Hylckama Vlieg 
1   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
,
Frits R. Rosendaal 
1   Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
› Author Affiliations
Funding The study was funded by the Dutch Ministry of Health, Welfare and Sport (reference number 333053).
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Abstract

Background

The magnitude of the risk of venous thromboembolism (VTE) after SARS-CoV-2 vaccines is debated.

Methods

We included patients with a first VTE in 2021 and controls from a sample of Dutch citizens. Participants completed a questionnaire on VTE risk factors and vaccination, with data linked to Statistics Netherlands. Odds ratios (OR) with 95% confidence intervals (95%CI) expressed the relative rate of VTE within 28 days post-vaccination, adjusted for age, sex, BMI, month of index date, and major VTE risk factors (COVID-19, surgery, cancer, and immobilization). Using previously reported age-stratified VTE incidences, we estimated vaccination's net impact by comparing the number of events attributed to vaccination and prevented by vaccine-induced protection against COVID-19-associated VTE.

Results

We included 779 VTE patients and 5,311 controls. mRNA vaccines were not associated with VTE risk (BNT162b2 [Pfizer- BioNTech] vaccine OR 1.0, 95%CI 0.7–1.3; mRNA-1273 [Moderna] vaccine OR 1.4, 95%CI 0.8–2.4). Vector-based vaccines were associated with VTE risk (AZD1222 [AstraZeneca]: OR 1.5, 95%CI 1.0–2.5; Ad26.COV2.S [Johnson & Johnson]: OR 2.9, 95%CI 0.9–9.2). Excluding participants with major VTE risk factors, risks changed (BNT162b2: OR 1.5, 95%CI 1.1–2.1; mRNA-1273: OR 0.8, 95%CI 0.3–2.3; AZD1222: OR 2.0; 95%CI 1.0–3.9; and Ad26.COV2.S: OR 3.4; 95%CI 0.7–15.5). We estimated that SARS-CoV-2 vaccines contributed to approximately 700 VTEs but prevented approximately 3,700 VTEs.

Conclusion

SARS-CoV-2 vaccines are associated with VTE, with varying risks between types of vaccines, and by sex and age. On a population level, in the Netherlands in 2021, SARS-CoV-2 vaccination resulted in a net benefit for the number of VTE events.

Keywords

venous thrombosis - SARS-CoV-2 vaccines - case control - population attributable fraction

Note

The following persons contributed to the recruitment of patients: Eva Kempers and Marieke J.H.A. Kruip (Erasmus University Medical Center, Rotterdam); Frederikus A. Klok (Leiden University Medical Center, Leiden) Jenneke Leentjens and Saskia Middeldorp (Radboud University Medical Center, Nijmegen), Cees van Nieuwkoop (Haga Teaching Hospital, The Hague), Maurice A.A.J. van den Bosch (Santeon collaboration), Peter. W.A. Kunst (Onze Lieve Vrouwe Gasthuis, Amsterdam); Jan G. den Hollander (Maasstad Hospital, Rotterdam); Maaike Söhne (Antonius Hospital, Nieuwegein); Henk Kramer (Martini Hospital, Gronginen); Heidi S.M. Ammerlaan (Catharina, Eindhoven); Anne Esselink (Canisius-Wilhelmina Ziekenhuis, Nijmegen).


Ethics Approval Statement

The study was approved by the scientific committee of the Department of Clinical Epidemiology Leiden University Medical Center (reference number A175). The Medical Ethics Committee of the Leiden University Medical Center exempted this study from the Medical Research Involving Human Subjects Act (reference number nWMODIV2_2022026).


Data Availability Statement

STATA code is available upon request from the corresponding author. The data underlying this article cannot be shared publicly due to ethical reasons and confidentiality agreements between the researchers and both the participants and Statistics Netherlands.


Authors' Contribution

W.J.v.D.: design, recruitment, data collection and analyses, and writing the manuscript; A.C.K. and A.v.H.V.: revised the manuscript; F.R.R.: supervised the project.


Supplementary Material



Publication History

Received: 14 March 2025

Accepted: 18 July 2025

Article published online:
08 August 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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