Cerebral venous sinus thrombosis (CVST) was more frequently reported after AstraZeneca (ChAdOx1 nCov-19) vaccination than after any of the other SARS-CoV-2 vaccines, an analysis of cases notified to the European Medicines Agency (EMA) revealed. Patients with CVST after AstraZeneca vaccination had a higher mortality rate compared with pre-COVID-19 CVST controls and patients with CVST after mRNA vaccination.
When the first cases were reported of CVST with thrombocytopenia after vaccination against SARS-CoV-2 infection, without any known causal relationship, a study was quickly initiated to investigate this [1,2]. The study’s aim was 2-fold: to report clinical data of patients who developed CVST after SARS-CoV-2 vaccination and to compare data between different vaccines and with a pre-COVID-19 CVST control group.
Data was retrieved from the so-called EMA EudraVigilance database. Dr Jonathan Coutinho (Amsterdam University Medical Centre, the Netherlands) and colleagues collected all cases coded as CVST and additionally screened for “potential CVST” (for example cerebral thrombosis or auto-immune heparin-induced thrombocytopenia). As control group served 100 European patients with CVST from before the COVID-19 pandemic. In total, 213 CVST cases were identified: 187 after AstraZeneca/Oxford (ChAdOx1 nCov-19) vaccination and 26 after mRNA vaccination (25 with Pfizer/BioNTech [BNT162b2], 1 with Moderna [mRNA-1273]).
As expected, most patients were <60 years of age with no significant age differences between the 3 groups. Around half of patients with CVST after AstraZeneca vaccination had concomitant thrombocytopenia. Here, between-group differences were substantial: 107/187 in the ChAdOx1 nCov-19 group, 0/26 in the mRNA vaccine group, and 7/100 in the pre-COVID-19 group. The corresponding mortality was also substantially higher in the ChAdOx1 nCov-19 group (see Table for the full results). Mortality in patients with thrombocytopenia in the ChAdOx1 nCov-19 group was 49% (95% CI 39%–60%).
Table: Comparison of CVST cases after ChAdOx1 nCov-19, mRNA vaccines, and pre-COVID-19 CVST cases 
CVST, cerebral venous sinus thrombosis; PCR, polymerase chain reaction; VTE, venous thromboembolic events.
Reprinted from Krzywicka K, et al. Eur J Neurol. 2021;28(11):3656–3662. DOI 10.1111/ene.15029 under the terms of the Creative Commons Attribution 4.0 license.
Limitations of the study were limited availability of clinical data (since a passive pharmacovigilance database was the source), risk of selective reporting (or underreporting), mortality rates reflect the first experience with vaccine-induced immune thrombotic thrombocytopenia (VITT), lack of a central adjudication of the CVT diagnosis, and absolute CVT risk after vaccination could not be calculated in this study.
This study confirmed that CVST after ChAdOx1 nCov-19 vaccination has distinct features that differ from patients with CVST unrelated to vaccination. To prove causality, investigations for potential alternative causes are necessary.
- Coutinho, JM. Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency. PLEN04, EAN 2022, 25–28 April, Vienna, Austria.
- Krzywicka K, et al. Eur J Neurol. 2021;28(11):3656–3662.
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