Johnson & Johnson’s one-shot Covid-19 vaccine is expected to go into use here shortly after the European Medicines Agency (EMA) this week confirmed that its benefits outweigh any risk of a very rare side effect of abnormal blood clots.
Minister for Health Stephen Donnelly has said it will be early next week before the National Immunisation Advisory Committee (Niac) issues recommendations on its deployment. But with people needing only one dose, it could significantly accelerate the vaccine rollout. After rare blood clotting episodes were linked to the AstraZeneca vaccine, Niac advised that it should not be used for anyone under the age of 60.
Public trust is vital, as any mention of possible side effects triggers emotions that cloud rational thinking. Here, we ask experts to answer the key questions members of the public might have.
Are these "abnormal" blood clots the same as those already associated with the AstraZeneca vaccine?
"Very similar", according to the EMA. The eight cases it studied, which were potentially linked to the Johnson & Johnson vaccine in the US, involved a rare combination of unusual blood clots and low levels of platelets in the blood. They were all in people aged under 60 and mostly women, but the EMA says specific risk factors have not been confirmed.
At the beginning of April, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, where the AstraZeneca vaccine has been used extensively, reported 30 cases (out of 18 million people vaccinated with it) of rare blood clots, including seven deaths, but it is not clear if they were a coincidence or a real side effect.
How rare is "rare"?
Extremely. The cases appear to be just under one in a million with the J&J vaccine. The MHRA's findings referred to above would work out at just under two in a million with the AstraZeneca. In the cases of both vaccines, the EMA has now said these blood clots should be listed as "very rare side effects".
These issues have sparked comparisons to the much greater likelihood of blood clots, say, for women taking oral contraceptives. Describing that as a "false equivalency", Dr Michelle Lavin, consultant haematologist in the National Coagulation Centre at St James's Hospital in Dublin and an RCSI researcher at the Irish Centre for Vascular Biology, says such commentary does, however, illustrate how "every day we take medicine and every individual balances the risk and the benefit of that medication".
She refers to a study that found, among women of child-bearing age, the risk of venous thromboembolism (VTE), a blood clot that starts in the vein, is four per 10,000 women per year. This rises to between seven and 10 per 10,000 among women using a combined oral contraceptive, which incorporates both oestrogen and progesterone.
However, this increases again to 20-30 per 10,000 women during pregnancy and the 12 weeks afterwards, with the postnatal period being particularly high-risk. This has nothing to do with medication and is all about nature, at a time when clotting factors in the blood multiply to defend against blood loss in birth.
While hormone replacement therapy also carries an elevated risk of blood clotting, the NHS in the UK estimates that for every 1,000 women taking HRT tablets for 7½ years, fewer than two will develop a blood clot.
More to the point, blood clotting is a feature of Covid-19 illness, which these vaccinations prevent. Various studies have recorded blood clots in 30 to 50 per cent of Covid-19 patients in intensive care, says Lavin. Typically, blood clotting would occur in five to 10 per cent of ICU patients.
But if all those are "normal" blood clots, what is "abnormal" about the ones being reported as a possible vaccine side effect?
There are two unusual features of these clots: first, the site of the clotting, which tends to be the blood vessels around the brain or the gut; second, they are associated with a drop in blood platelet counts.
“That doesn’t happen in a typical thrombosis,” says Lavin. It suggests that it may be an unusual response from the immune system, although nothing is proven yet.
Generally, blood clots form in the leg, above and below the knee. The ones above the knee are more likely to break off and move through the circulation system to lodge in the lungs, which is known as pulmonary embolism. Up to 10 per cent of those cases are fatal, which is why early recognition of leg swelling is so important.
Clots in the blood vessels surrounding the brain are known as cerebral venous sinus thrombosis (CVST) and usually affect between four and 12 people in one million each year.
Have these unusual blood clotting events been seen before?
They're similar to rare instances of an immune reaction to the blood-thinning drug heparin, which is commonly used to prevent and treat thrombosis. It's standard practice for hospital patients to be given heparin, as immobility is a high-risk factor for clots, but very occasionally there will be an adverse reaction to this drug, causing low platelets and thrombosis.
It’s “extremely rare”, says Lavin. “But it’s something that we are familiar with, and we would manage patients occasionally with this condition.”
As there seemed to be a similar pattern among the cases being looked at in relation to the two vaccines, “people started to follow the same track that we would follow for this heparin-induced phenomenon”.
It’s “probably a slightly different pathway but the same end result, an immune-based phenomenon that can occur very rarely,” she suggests, while pointing out that as the use of every drug is a risk-benefit balance: “We still use heparin all the time because it is a very good drug to prevent clots and treat clots but very, very rarely can have these side effects.”
What would the symptoms be?
Unexplained bruising, away from the injection site would be one says Lavin. Numerous red dots on the skin or bleeding from gums are also signs of low platelets. Other symptoms, about which people should be vigilant for up to 30 days post-vaccination, include stomach pain or severe headaches that are not improving.
Those are not to be confused with headaches, which are an extremely common reaction in just the first 24 to 48 hours after a vaccination.
One good thing to come out of all this talk of rare clots is awareness-raising around the common ones, says Lavin. Pain, swelling and redness in a leg can indicate clots there, but shortness of breath, chest pains and coughing up blood can be signs they have moved to the lungs.
Are people with a history of thrombosis or bleeding disorders at greater risk of these rare complications?
No, says Lavin. Such patients (who can find more advice on stjames.ie/services/hope/nationalcoagulationcentre) are being advised to take whichever vaccine is offered to them in the national vaccine roll-out.
Is there something different about these two vaccines and others being used here?
The technology of these two vaccines differ from that of the Pfizer-BioNTech and Moderna equivalents. The latter are what are called mRNA vaccines, whereas the Johnson & Johnson and AstraZeneca are adenovirus vectored vaccines.
But the use of an adenovirus vector is not a whole new approach, says Lavin. It is a technological backbone that has been adapted for the prevention of Covid. She stresses that “all these vaccines have been proven to be very efficacious in preventing severe Covid and hospitalisation and I hope people don’t forget that”.
Going by the figures, the risk of developing these abnormal clots after receiving the vaccines seems tiny. So why is it scaring people?
Humans in general are poor at judging risk because calculating probabilities does not come naturally to us, says Brian Hughes, a professor of psychology at NUI Galway and a chartered member of the Psychological Society of Ireland.
Proper risk assessments should combine two factors: impact and probability. In other words: “how bad something is” and “how likely it will happen”. But we tend to focus on the first.
“If we feel the outcome is especially bad, we react to it with fear, and we become motivated to avoid it. In contrast, probability is a much more abstract concept and does not provoke the same emotional response.”
In other words, we care about tangible outcomes that we can visualise but don’t care about probability statistics that we must compute in our heads.
Also, we often falsely compare “risk” with “no risk”, says Hughes. “With the vaccines, we might think about the risk of blood clots and decide it is safer not to be vaccinated. But we forget that the alternative to this risk is not ‘no risk’. If we don’t get vaccinated then we remain exposed to Covid and could get seriously ill.”
Niac has been advising, for instance, that people aged 60-64 are 85 times more likely to die from Covid-19 than to develop any blood clotting – rare or otherwise – after being vaccinated. So, for anybody in that cohort to refuse the AstraZeneca on risk grounds makes no statistical sense.
Yet, as Hughes adds, some people seem to find this blood clot scenario more frightening than the continuing risk of Covid-19. Which is ironic, considering that blood clots have been so prevalent among the nearly 7,000 people who have died on this island with Covid-19.