Several European countries have suspended distribution of the AstraZeneca vaccine following reports of thrombocytopenia and thrombotic complications. To date, there have been 15 cases of deep-vein thrombosis and 22 cases of pulmonary embolism reported with the vaccine in the EU and UK (www.astrazeneca.com/media-centre/press-releases/2021/update-on-the-safety-of-covid-19-vaccine-astrazeneca.html).

The European Medicines Agency has stated that it believes that the benefits of the AstraZeneca vaccine outweigh the risks of side effects, although the EMA’s safety review has not been completed (www.ema.europa.eu/en/news/emas-safety-committee-continues-investigation-covid-19-vaccine-astrazeneca-thromboembolic-events). Health Canada, which relies on other countries to conduct safety reviews, has also stated that the benefits outweigh the risks.

COVID-19 is known to be associated with thromboembolic complications (Castro et al. Cardiol Rev 2021;29:43-44). Indeed, the Centers for Disease Control (CDC) vaccine safety database has recorded only three cases of venous thromboembolism in vaccinated individuals compared to 408 cases in non-vaccinated individuals (Shimabukuro T. COVID-19 safety update, 27 January 2021, www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-01/06-COVID-Shimabukuro.pdf).

However, the background incidence of thromboembolism is arguably beside the point. At issue is whether there is an increased incidence of thromboembolic complications with the AstraZeneca vaccine relative to other COVID-19 vaccines. A further consideration is whether the underlying pathophysiology differs. Case reports include seven cases of central venous thrombosis, a rare form of stroke, as well as widespread clot formation in large and small vessels, thrombocytopenia and internal bleeding, a syndrome resembling disseminated intravascular coagulation (Vogel et al. Science, 17 March 2021; www.sciencemag.org/news/2021/03/it-s-very-special-picture-why-vaccine-safety-experts-put-brakes-astrazeneca-s-covid-19). Some have speculated that the SARS-CoV-2 Spike proteins cause abnormal complement activation, which may be exacerbated by vaccines using the Spike protein as the antigen (Yu et al. Blood 2020;136:2080-2089). Another suggestion is that CoV-2-reactive antibodies may have pro-apoptotic and/or pro-coagulant effects on platelets (Bollmann A. Br Med J, 16 March 2021. www.bmj.com/content/372/bmj.n699/rapid-responses).

At present, it is not known if thrombocytopenia/thromboembolism is associated with COVID-19 vaccination, or if the incidence of these complications is uniquely higher with the AstraZeneca vaccine. It also remains to be determined if pre-existing thrombocytopenia, as seen in some treated multiple sclerosis patients, increases the risk of thrombosis during the pandemic.