Concerns have been mounting over reports of rare but serious blood clots in a small number of recipients of the Oxford/AstraZeneca vaccine, leading to a UK recommendation on Wednesday that healthy adults under 30 should have an alternative jab if they can. We take a look at the latest information and guidance.
What are the potential side-effects from Covid vaccines?
All medications including vaccines have some side-effects. The most common with the Covid jabs are mild and short-lived, including localised soreness, fatigue or aches and headaches.
However the Oxford/AstraZeneca jab has been linked to a small but concerning number of reports of blood clots combined with low platelet counts (platelets are cell fragments in our blood that help it to clot).
These include a rare clot in the brain called cerebral venous sinus thrombosis (CVST). In an unvaccinated population, upper estimates suggest there may be 15 to 16 cases per million people per year. But also highly uncommon is the combination of CVST or other rare clots with low platelets, and sometimes unusual antibodies – and that combination is at the centre of current concerns.
The Medicines and Healthcare products Regulatory Agency (MHRA) said recipients of the Oxford/AstraZeneca jab should look out for new headaches, blurred vision, confusion or seizures that occur four days or more after vaccination.
While headaches are very common post-vaccine, Dr Josh Wright, vice-president of the British Society for Haematology, stressed that those linked to CVST are unusually severe and persistent and progressively worsen over a period of days. Most cases are reported within two weeks of someone having the jab.
The MHRA also flagged shortness of breath, chest pain, abdominal pain, leg swelling and unusual skin bruising as reasons to seek medical advice.
Once identified, the symptoms can be treated. Beverley Hunt, professor of thrombosis and haemostasis at King’s College London and a representative of Thrombosis UK, said the first step would be to give a dose of intravenous gamma globulin – essentially giving concentrated antibodies which block the effect of the antibodies that could be causing the clotting problems. Once the patient is stable this is then followed by giving them anticoagulation agents, but which are not heparins.
How many cases have there been?
Up to and including 31 March, the MHRA said it received 79 reports of cases of blood clots combined with low platelets, including 19 deaths, following more than 20m doses of the Oxford/AstraZeneca jab. That equates to about four cases for every million vaccinated individuals.
The MHRA added that 44 of the reports and 14 of the deaths related to CVST with a low platelet count. Of the 19 deaths, 11 were in people under the age of 50 and three were in people under the age of 30.
Two cases of blood clots with a low platelet count have also been reported among recipients of the Pfizer/BioNTech jab. “This is a particularly rare and very unique form of abnormal clotting,” said Wright.
The European Medicines Agency is also examining three cases of venous thromboembolism blood clots involving the Johnson & Johnson jab.
The MHRA says blood clots combined with low platelets can occur naturally in unvaccinated people as well as in those who have caught Covid, and that while evidence of a link with the Oxford/AstraZeneca vaccine has become stronger, more research is needed.
How may the vaccine cause these problems?
At present the mechanism by which the jab could cause clotting problems remains unclear. But experts have noticed a similarity to a clotting event sometimes seen among people given the blood-thinning drug heparin, whereby antibodies are generated that result in platelets becoming activated.
“In very rare situations heparin can actually cause this platelet activation problem and lead to blood clots in unusual places. So there are some similarities between these two conditions,” said Wright.
According to Hunt, one possibility is that the Oxford/AstraZeneca vaccine may also trigger the production of antibodies that activate platelets, causing them to form clots. In the process, platelets are used up, resulting in a fall in the platelet count.
What is the current official recommendation?
The MHRA, along with the EMA and the World Health Organization (WHO), have all repeatedly said people should continue taking the Oxford/AstraZeneca shot because its benefits in preventing Covid infection far outweigh any risks.
However on Wednesday the MHRA acknowledged a possible link between the jab and the clots, adding that careful consideration should be given to those who may be at higher risk of certain types of blood clots.
In addition, the UK’s Joint Committee on Vaccination and Immunisation (JCVI) said it was recommending that people aged 18-29 should be offered other Covid vaccines – if available – provided they are healthy and at low risk of Covid. There are about 10m 18 to 29-year-olds in the UK.
“Although the chance of any person receiving the vaccine experiencing a blood clot with low platelets is extremely small, because the risk of severe Covid in the under-30s with no underlying illness is also small, JCVI feel as a precautionary measure it is appropriate for those in this age group to be offered an alternative Covid vaccine when their turn comes for their first dose of a vaccine,” said Prof Anthony Harnden, deputy chair of the JCVI.
Pregnant women should discuss with their doctors whether to have the Oxford/AstraZeneca jab as pregnancy can increase the risk of blood clots, the MHRA said.
Meanwhile on Wednesday the EMA said the rare clotting syndrome should be listed as a very rare side-effect of the Oxford/AstraZeneca jab after reviewing 62 cases of CVST and 24 cases of splanchnic vein thrombosis, largely from Europe and the UK where 25m doses of the jab have been given. Of these cases, 18 were fatal.
“So far, most of the cases reported have occurred in women under 60 years of age within two weeks of vaccination,” the EMA said, although specific risk factors have not yet been confirmed.
According to data from the MHRA, 51 of the 79 clotting cases and 13 of the deaths were in women, although women were more likely to receive the Oxford/AstraZeneca jab than men.
Should people take aspirin after the vaccine?
There has been no advice that anyone should take medication to prevent rare clotting events. Hunt cautioned against taking aspirin, stressing it is thought the clotting problems are down to an immune response.
“So taking aspirin is not going to be helpful. Taking an anticoagulant probably isn’t going to be helpful, especially if you are going to get a low platelet count, it will increase your risk of bleeding,” she said. “And we know if you take aspirin and you don’t need to take aspirin the benefits aren’t very good and there is a risk that you can bleed spontaneously.”
Does the contraceptive pill increase women’s risk of blood clots more than the Oxford/AstraZeneca jab?
Combined hormonal contraceptives, which contain oestrogen, have been associated with an increased risk of blood clots including CVST, deep vein thrombosis and pulmonary embolism.
According to an EMA review in 2014, the risk of blood clots ranged from five to 12 cases per 10,000 women who take combined hormonal contraceptives for a year, compared with two cases each year per 10,000 women who are not using such contraceptives. “The combined oral contraceptive pill is probably the commonest cause of cerebral sinus thrombosis, so it is a very good comparison,” said Hunt.
Adam Finn, professor of paediatrics at the University of Bristol and a member of the JCVI, said other risk-benefit comparisons can also be made. “We’ve seen data that the annual risk of dying in a car crash if you regularly travel in a car is about 1 in 20,000, with a lifetime risk of about 1 in 240,” he said. “We take those risks for granted.” The faculty for sexual and reproductive health stressed the risk of blood clots from the pill was also low – much smaller than the risk of having a blood clot if they were pregnant.
Should you have a second dose of the Oxford/AstraZeneca jab?
The vast majority of people who had a first dose of the jab, including under-30s, should get their second dose, with some exceptions.
“Anyone who experienced cerebral or other major blood clots occurring with low levels of platelets after their first vaccine dose of Covid-19 Vaccine AstraZeneca should not have their second dose,” the MHRA said. “Anyone who did not have these side-effects should come forward for their second dose when invited.”
All 79 cases detailed by the MHRA occurred after the first dose, but that could be because far more people have received their first dose than their second.
Could other Covid vaccines cause these clotting problems?
Harnden said at present this is unclear. “Because we don’t know what the causal mechanism is yet – and although there is a strong possibility that this is caused by the Oxford/AstraZeneca jab, we are not 100% certain – we can’t really postulate [about] other [vaccine] types at the moment,” he said.
But the occurrence of only two cases of blood clots and low platelets among those vaccinated with the Pfizer jab suggests the problem is linked to the Oxford/AstraZeneca jab, he said.
One possibility is that it is linked to the type of vaccine, with the EMA examining whether other vaccines using similar technology to the Oxford/AstraZeneca vaccine posed any risk.
The Janssen (Johnson & Johnson) vaccine also uses a modified cold virus to introduce the instructions for the spike protein into our cells – but whereas the Oxford/AstraZeneca vaccine uses a chimp adenovirus, the Johnson & Johnson vaccine uses a human cold virus.
Dr Peter Arlett, head of data analytics and methods taskforce, said so far there had been three cases of venous thromboembolism blood clots involving the Johnson & Johnson jab.
“However the numbers are extremely small compared to the 5 million patients that have received the Johnson & Johnson vaccine worldwide. This is, however, under close scrutiny, the [committee] is looking at it carefully, and I think it would be fair to say there’s intensive monitoring of this issue across the vaccines.”
When did reports of problems first emerge and how did countries respond?
Norway and Denmark were the first to temporarily halt the Oxford/AstraZeneca shot on 11 March after reporting several cases of CVST combined with a low count of blood platelets.
Austria, Bulgaria, Cyprus, Denmark, Estonia, France, Germany, Ireland, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Portugal, Slovenia, Spain and Sweden, along with non EU-members Iceland and Norway, subsequently either paused the vaccine or banned the use of particular batches.
Germany’s health ministry in particular said it had a “legal obligation” to pause the jab pending investigation by the EMA. It said the incidence rate of the events in Oxford/AstraZeneca recipients appeared three or four times higher than would normally be expected, with young women seeming to be over-represented, and it had “a duty of care”.
Not all countries followed suit: Belgium’s health agency said it would keep using Oxford/AstraZeneca as to stop vaccinating people in the face of rising cases would be “irresponsible”. On Wednesday, Belgium announced it would restrict the jab to over-55s.
What restrictions have countries placed on Oxford/AstraZeneca’s use?
Most countries have already resumed innoculations with the Oxford/AstraZeneca vaccine, although often with restrictions. But Denmark and Norway have prolonged their initial suspension of the shot until mid-April pending further investigations.
Countries that have resumed use without restrictions include: Austria, Bulgaria, Cyprus, Iceland, Ireland, Latvia, Lithuania and Romania. Italy has said people who do not want Oxford/AstraZeneca may have another vaccine later.
Countries that have imposed restrictions on the shot’s use include Canada (limited to people aged 55 and over); Finland (65 and over); France (55 and over); the Netherlands (60 and over); and Sweden (65 and over).
Germany is offering the shot only to people aged 60 and over and in high-priority groups, with under-60s who have had a first shot recommended to get a different one, and Spain is giving it to only to those aged 55-65, plus essential workers over 65. Belgium is limiting it to over-55s.
This content first appear on the guardian