Are blood clots a concern with mRNA vaccines?

The rare risk of blood clots associated with the AstraZeneca vaccine are now well known, but last week concerns started to emerge about Pfizer.
 
A 40-year-old police sergeant from Brisbane made headlines after he developed a blood clot on Wednesday, just three days after receiving the mRNA vaccine.
 
A statement released by Queensland police on Friday revealed the man, who works in the state’s hotel quarantine system, is back on duty and that he has a history of clotting.
 
‘The sergeant previously underwent surgery on his knee in 2009 and developed deep vein thrombosis following this procedure. He recovered from this diagnosis within 12 months,’ the statement read.
 
On Wednesday, a Department of Health (DoH) spokesperson said that the Vaccine Operations Centre is ‘working closely with Queensland Health to investigate’; however, when approached for comment, a Queensland Health spokesperson told newsGP the case is a Federal matter.
 
‘In Queensland, all adverse events in relation to the COVID-19 vaccines are reported to the Therapeutic Goods Administration [TGA],’ the spokesperson said. ‘The TGA will then undertake an assessment and determine whether there is any clinical link to the vaccination.’
 
It is the first suspected case of clotting associated with the Pfizer vaccine in Australia, and follows six cases of thrombosis with thrombocytopenia syndrome (TTS), one of which proved to be fatal, linked to the AstraZeneca vaccine.
 
The risk of blood clots is considered low, given that more than 1.7 million COVID vaccine doses have been administered in Australia to date. However, it remains unclear how many of these doses are Pfizer.
 
The European Medicines Agency (EMA) said last week that there have been more than 300 cases of TTS associated with coronavirus vaccines worldwide, including 287 occurrences with AstraZeneca, eight with Johnson & Johnson, 25 with Pfizer and five with Moderna.
 
According to Oxford-run website Ourworldindata.org, more than 951 million vaccines have been administered globally. But, the World Health Organization (WHO) has also warned that there is ‘limited post-market surveillance data’ on COVID-19 vaccines outside of AstraZeneca, Johnson & Johnson, Pfizer and Moderna, as well as vaccines administered in low- and middle-income countries.
 
Meanwhile, in the US, where more than 180 million doses of the Pfizer and Moderna vaccines have been administered, the Centers for Disease Control and Prevention (CDC) says there have been zero cases of TTS reported.
 
Professor Damian Purcell, a virologist from The Peter Doherty Institute for Infection and Immunity, told newsGP he is not surprised by the low occurrence of clotting associated with mRNA vaccines.
 
‘In general, the safety profile has looked very, very good,’ he said. ‘The thing that we were most concerned about initially [with mRNA vaccines] was the reactogenicity and the allergic responses.
 
‘But a lot of research has gone into engineering the RNA component to make it as silent as possible to what we call “innate immune responses”. So that’s part of the advancement in RNA technologies.
 
‘The thing that’s more complex, and probably is the component that’s overlapping with this complication of coagulation, is the biology of the expressed protein product of the vaccine – and this will go for many of the vaccines.
 
‘The spike protein and the coronavirus interaction with the ACE2 receptor can potentially cause issues because it seems the ACE2 receptor is present on platelets. So that can … lead to this complication.’
 
Professor Thomas Preiss, an RNA biologist from the Australian National University, says it is important to remember that beyond COVID and its associated vaccines that blood clots are not uncommon. The TGA recently noted that up to 50 blood clots occur daily in Australia.
 
‘This makes it very important, with any occurrence of blood clots after COVID-19 vaccination, to look carefully at what type of blood clot has occurred,’ Professor Preiss told newsGP.
 
‘First, the level of concern would vary strongly with the type of adverse outcome that patients might suffer from the type of blood clot.
 
‘Second, statistical data needs to be accumulated and then analysed to show whether specific types of blood clots are found more frequently with vaccinated people than in the general population.’
 
Overall, Professor Preiss says it ‘seems clear’ that blood clotting issues with any vaccine are very rare.
 
‘As I understand it there is some evidence that blood clotting may be mildly elevated with either the AstraZeneca or the Moderna and Pfizer/BioNTech vaccines,’ he said.
 
‘The more dangerous type – vaccine-induced immune thrombotic thrombocytopenia [VITT] – has only been confirmed as moderately elevated after vaccination with viral vectored [AstraZeneca and Johnson & Johnson] but not mRNA vaccines.’
 
According to recent research from Oxford University, recipients of AstraZeneca have a five per million chance of developing blood clots compared to four per million for Pfizer and Moderna. Meanwhile, the risk of blood clots from contracting COVID is around 8–10 times higher at 39 per million.
 
The WHO has said that work is ‘ongoing’ to better understand the risk factors for TTS.
 
With time, Professor Purcell says it is possible that a full analysis might allow scientists to find a ‘mechanistic basis’ to identify people who have some pre-existing propensity to make the antibody factors implicated in the heparin induced thrombocytopenia.
 
And while mRNA vaccines are a relatively new technology, Professor Purcell says that in itself may prove to be of benefit.
 
‘I do think that there’s a much lower immune legacy, if you like, with the RNA vaccines because we don’t have to contend with other pre-existing immune liabilities against adenoviruses,’ he said.
 
‘All of us have had adenovirus infections, which will impact on the efficacy potentially of those vaccines, particularly in the case of repeat vaccination, if we need those.
 
‘But it’s also potentially more specifically targeted for location of expression and this might actually end up being an important component of understanding how to mitigate these rare adverse events if it turns out that expression of spike protein format, where it comes into contact with platelets, might actually be something that is important to control.’
 
Pfizer has responded to the case of the Brisbane man, saying that it has undertaken a ‘comprehensive assessment’ of ongoing aggregate safety data, including a review of all adverse events received for the vaccine through to 27 March.
 
‘[The assessment] provided no evidence to conclude that arterial or venous thromboembolic events, with or without thrombocytopenia, are a risk associated with the use of our COVID-19 vaccine,’ the statement said.
 
It follows the Federal Government’s decision to prioritise Pfizer for people under the age of 50.
 
Based on the data, Professor Preiss says both viral vector and mRNA vaccines are beneficial, and that changing advice over time needs to be understood in context.
 
‘For example, a country with rampant COVID-19, a poor health system and no easy access to mRNA vaccines should continue vaccinating their population with the viral vector type as this will dramatically reduce serious illness and deaths,’ he said.
 
‘The equation is different for a country like Australia that is essentially free of COVID-19 and that has access to mRNA vaccine, albeit with some delays. Here, even a remote risk of vaccine side effect is a factor given that the population is not immediately at risk of suffering the serious consequences of COVID-19.’
 
The Department of Health was contacted for comment but did not respond prior to publication.
 
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