Thrombocytopenia

Rare side effect more frequent after adenovirus-based covid-19 vaccine than after mRNA vaccine

AstraZeneca’s adenovirus-based covid-19 vaccine is associated with a 30 percent increased risk of the rare side effect thrombocytopenia, or too few platelets, compared to Pfizer’s mRNA covid-19 vaccine. This has been confirmed by research coordinated by Erasmus MC’s Department of Medical Informatics, published in The BMJ.

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The researchers used data from millions of residents in Europe and the United States.

The study was prompted by reports to drug authorities of thrombosis combined with low platelets as a side effect of the covid-19 adenovirus-based vaccines from AstraZeneca and Johnson & Johnson. Despite the rarity – a few cases after millions of vaccinations – it was reason enough for the European Medicines Agency (EMA) to ask the scientific community to dig into this. Researchers led by Prof. Daniel Prieto-Alhambra of Oxford University and Erasmus MC’s Department of Medical Informatics accepted the challenge.

Millions of residents

The researchers used data from millions of residents in France, Germany, the Netherlands, Spain, the United Kingdom, and the United States to compare the risk of two groups of rare side effects between covid-19 vaccines. They looked at thrombosis combined with thrombocytopenia (TTS), and at thromboembolic events. It is the first study to directly compare vaccines from AstraZeneca, Janssen, Moderna, and Pfizer. In previous safety studies, unvaccinated individuals were compared with vaccinated individuals.

‘An increase of a few dozen people in a group of millions vaccinated’

The main finding is that AstraZeneca’s vaccine has a 30 percent increased risk of thrombocytopenia, or too few platelets, compared with Pfizer’s vaccine. The researchers also found what they call a trend towards an increased risk of thrombosis combined with low platelets (TTS) with the Janssen vaccine compared to mRNA vaccines, including Pfizer and Moderna.

‘We are less certain of this last result because we had too few cases in our data set. That says something about the rarity of the TTS side effect because we used data from millions of vaccinees’, Prieto-Alhambra says.

Type of vaccine

Thrombosis with or without thrombocytopenia are very rare side effects anyway, Prieto-Alhambra stresses. ‘Thirty percent increased risk may sound alarming, but in absolute numbers we are talking about an increase of a few dozen people in a group of millions vaccinated – according to our data.’

The differences between the vaccines, he says, probably have to do with the type of vaccine. AstraZeneca and Janssen are so-called adenovirus-based vaccines and Moderna and Pfizer are mRNA vaccines. ‘It seems that adenovirus-based vaccines have a higher risk of these side effects, but the exact mechanism behind this is difficult to investigate because of the rarity.’

No effect on booster campaign

It is important for drug authorities and vaccine manufacturers to take notice of these results. ‘Adenovirus-based vaccines are easy to modify. So for any future pandemics where these vaccines will come in handy again, it is good to take these rare side effects into account’, says Prieto-Alhambra. For the current Dutch booster campaign the results have no direct as no adenovirus-based vaccines are being used.

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