The announcement by the European Medicines Agency (EMA) that a possible link exists between vaccination with the AstraZeneca COVID-19 vaccine and development of very rare cases of unusual blood clots with low blood platelets must be kept in perspective. Vaccine safety is of the upmost importance and the EMA and other regulators (TGA, FDA) do need to investigate this adverse event while acknowledging the difficulties of linking cause and effect with new vaccines.

The Pandemrix vaccine for the 2009 H1N1 influenza (swine flu)pandemic was associated with an increased rate of narcolepsy in children. Initially it was the adjuvant used to boost the immune response that was suspected as the cause then the interaction between Pandemrix and the H1N1virus itself. After more than 10 years no specific linkage between the vaccine and the adverse event has been confirmed.

The rare unusual blood clots with low blood platelets described for the AstraZeneca vaccine has been suggested to be an immune response evoking a condition similar to patients treated with heparin (thrombocytopenia) how ever no definitive evidence is currently available to indicate this is the case.

The requirement to vaccinate large numbers of individuals quickly in a pandemic does not make it always practical to consider a complete medical history for every individual vaccinated. The level of hypercoagulability in an individual can vary considerably depending on several factors including: medications used, history of chronic inflammatory disease, abnormalities in blood coagulation, nephrotic syndrome, or regular use of hormonal contraception. All these variables will need to be considered carefully for any individual who experiences an unusual blood clot with low platelets after receiving the AstraZeneca COVID-19 vaccine.

Being able to link this rare adverse event to use of the AstraZeneca vaccine may, like the Pandemrix vaccine, prove to be inconclusive. It is however very important to highlight that the risk of developing a serious blood clot are incredibly small compared to risk of possible COVID-19 infection

While a definitive link is yet to be established, it seems the likelihood of a relationship between rare clotting issues and the AstraZeneca vaccine has increased with increasing numbers being reported. These events are still very rare but seem to be more common in younger people thus prompting the European Medicines Agency to offer people less than 30 an alternative vaccine. Overall it still appears the benefits outweigh the risks, however the difference between the benefits and risks is less in younger people who are at lower risk of more significant consequences of COVID-19.

To keep in context, unfortunately no medical intervention is free of risk, and the risk of these clotting issues remains exceedingly rare at less than 5 per million doses administered. For comparison, a very common intervention in the form of the oral contraceptive pill carries a risk of clotting issues in the order of four of every 10 000 people taking this pill. When assessing the risks and benefits we also have to keep in mind the risks of not vaccinating.

While our control of COVID-19 in Australia has been exceptional, this has relied on many mitigation strategies including border controls and lock downs that will have to continue if our rate of vaccination is insufficient. Limitations on supply and logistical challenges with our current alternative, the Pfizer vaccine, may make the strategy of offering an alternative vaccine in this country challenging.

We do have an additional vaccine that will likely become available in the latter part of this year, the Novavax vaccine, however while it is looking very promising in terms of safety and efficacy, we do not currently have sufficient clinical trial data to commence using this vaccine. Overall the key currently is to provide as much information as possible on these risks so that they can be accurately weighed up against the benefits while we wait for further information from relevant regulators, further research as to risk factors, diagnosis and management of these clotting issues and for more alternatives to become available.

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All newly approved medicines have robust monitoring to identify side effects too rare to be detected in clinical trials. Blood clots are a serious health problem that occur in about one in every million people each year.

Early monitoring data of the AstraZeneca vaccine has shown that blood clots in those recently vaccinated may be more common, perhaps as often as 1 in every 200,000. This is not unique to the vaccine, and many commonly used medicines also carry a risk of blood clotting. This can occur when a person’s immune system mistakenly mounts a response against their own blood platelets, upsetting the delicate balance of blood.

While serious, it is important to note that the risk is rare and for more than 99.999% of people it will not be a concern. Therefore the rationale for getting vaccinated in the context of a global pandemic remains abundantly clear. The Thrombosis and Haemostasis Society of Australia and New Zealand have produced guidelines on detection and management of clots after vaccination ( https://www.thanz.org.au/resources/covid-19),which will further improve safety.

Everything we do in life –every medication we take, every vaccine we give – has a risk. It is a very safe vaccine but that doesn’t mean that occasionally some very rare side effects won’t occur and that’s what we’re seeing. People just need to be aware that every day we balance risk versus benefit, usually without thinking about it.

In Australia there is a one in a million chance of dying from a car crash every time you drive 400 kilometres. Based on the current data from the UK this is the same level of risk as dying from a severe blood clot from the AstraZeneca vaccine. The risk of dying from an anaesthetic in Australia is five times that, but most people wouldn’t let that put them off having surgery, even if it wasn’t urgent.

I know the government is considering all of the advice out of Europe right now and we’re going to have to have a serious discussion around the increased risk of getting this rare complication and whether we think that risk is sufficient to make a change to the recommendations around who gets the AstraZeneca vaccine.

Vaccination will be vitally important to conquer the COVID-19 pandemic, but safety concerns must never be overlooked. Without swift action there is a major risk to      the public's trust in the integrity of Australia's vaccine programs.

It is concerning that the Australian Federal Health Department has been so slow to respond to concerns expressed by many international regulators regarding evidence      that the AstraZeneca vaccine is causing a syndrome of immune thrombocytopenia and venous thrombosis.

Already one case of this vaccine-induced venous thrombosis syndrome has been reported in Australia, and more can be expected as the CSL/AstraZeneca vaccine      continues to be rolled out by the Federal Government. The question is what is an acceptable level of risk - a question that should be answered by the Australian public, not by the government on their behalf.

Several weeks ago, scientists in Germany, Austria and Canada https://www.researchsquare.com/article/rs-362354/v1 made a major breakthrough in identifying the mechanism behind these thrombotic events in people receiving the AstraZeneca vaccine, showing affected patients had anti-platelet antibodies that were driving the      thrombosis in a manner mimicking heparin- induced thrombocytopenia, a syndrome well-known to most doctors.

The study concludes: 'The AZD1222 vaccine is associated with development of a prothrombotic disorder that clinically resembles heparin-induced thrombocytopenia but      which shows a different serological profile.'

The risk may be as high as 1:200,000 across everyone immunised, but the rate could be far higher in younger people particularly women who seem to be at highest      risk. Currently as high as 50 per cent of those affected, have died as a result.

When some overseas regulators say the benefits may still outweigh the risk they are referring to a situation where potentially the vaccine could still save more lives from COVID-19 related deaths than are lost due to this syndrome.

In the context of Australia where we currently have no COVID-19 deaths, the risk-benefit relationship of the AstraZeneca vaccine is very different, particularly when other vaccines are potentially available that do not appear to share this risk.

There is an important dialogue on vaccine risk-benefit that has to be had with the Australian public. It is particularly important that the government’s vaccine advertising campaign be honest and transparent and should include warnings of potential side effects that in rare cases could be severe and life threatening.

It appears very likely that the AstraZeneca vaccine triggers a unique immune reaction characterised low platelet count and clotting. This is similar to another relatively rare, but serious clotting condition, caused by the use of heparin. This type of immune reaction involves platelets and white blood cells, and that is the reason for the development of severe clotting. In both cases, clotting appears within two weeks of administration of the substances.
 
Clotting is seen in arteries and veins at unusual sites in the brain and abdomen and mortality is high.
 
It should be emphasised that so far these are considered rare events and the benefits of the vaccine still outweigh the risks.  A cautious approach is recommended since specific risk factors are currently unknown. More research into the causes, risk factors and treatments are urgently needed.

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