This study, including data from Danish and Norwegian healthcare registries, reports the rates of thrombosis (in veins and arteries) within 28 days of the Oxford-AstraZeneca COVID-19 vaccine.  They compared these rates to those expected within the general population for people matched for gender and age.  The study showed more venous thrombosis than expected in the general population, and this signal was strongest for those occurring in the veins of the brain (cerebral venous sinus thrombosis, CVST).

The authors tried to adjust their analyses for other things that can cause thrombosis, for example the use of the oral contraceptive pill.  However, the study was limited by a lack of detail on how the diagnosis of thromboses was confirmed.  This is relevant as they can be difficult to diagnose without the correct scans and clinical expertise.  There is also a possibility that more thromboses were seen after vaccination partly because doctors were looking harder for them given previous reports of this complication.  Finally, the general population from which expected rates were determined might have been different to those vaccinated (mainly health and social care workers) which could also affect the risk estimates.

Nevertheless, the findings of this study are consistent with previous smaller case series suggesting an association of CVST with this type of vaccine, so further strengthen the idea that they are connected, especially with increasing evidence of abnormalities in the blood including low platelet levels and antibodies against platelet-factor 4 (PF4) associated with thrombosis after vaccination.

However, importantly, the absolute risk of thrombosis after vaccination in this large population-based study from two countries was very small, and strongly suggests that the benefits of vaccination in reducing COVID-19 infection and its consequences (which include a high rate of thrombosis in serious disease) still outweigh the risks.  More research is needed to study the detailed features and optimal treatment of arterial and venous thromboses, including CVST after this type of vaccine for COVID-19.

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This is a well-conducted study related to the current questions about clotting disorders and the AZ COVID-19 vaccine.  Using national health record data from Denmark and Norway, the investigators found a higher rate of venous thromboembolism in people receiving the vaccine than would have been expected based on general population rates.  There was some evidence that this risk may be restricted to women but once the data are split between men and women, the number of individuals having outcomes becomes smaller and it becomes more difficult to draw firm conclusions.  The increased risk was seen in all ages from 18-65 years, but there was a hint that any effect may be slightly greater in younger people.  Reassuringly, there was no evidence of an increased risk of some of the most common clotting problems we see including heart attacks and most types of stroke, but there was an increased rate of some more rare types of stroke such as cerebral venous thrombosis.  There was also a very small possible increased risk of platelet/clotting disorders and bleeding reported.  The authors also rightly pointed out that they were unable to study people having a combination of thrombotic events happening at the same time as low platelets which is the newly emerging syndrome that medicines regulators are trying to investigate.

What is important to note is the rare occurrence of the clotting problems in this study, with around one excess venous thromboembolism observed per 10,000 people receiving the vaccine.  In my view this does not offset the known benefits of the AZ vaccine in drastically reducing the risk of COVID-19 both at an individual and population level.  As more studies emerge, it is likely that over the coming weeks and months we will gradually discover more about these possible problems with the AZ vaccine, including whether there are people we can identify in advance as being at higher risk of having clot related side effects.

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