What We Know So Far About AstraZeneca Vaccine Blood Clot Link
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European regulators this week acknowledged a potential link between the Oxford/AstraZeneca Covid-19 vaccine and extremely rare blood clotting disorders.
What scientists and regulators don't yet know is how exactly the vaccine might be causing them.
As investigations continue, EU countries and the U.K. Have taken national decisions to either continue use or to restrict the vaccine to certain age groups.
Here's what we know so far based on public briefings from both the European Medicines Agency (EMA), the U.K.'s Medicines and Healthcare products Regulatory Agency (MHRA), and a subsequent press briefing involving scientists in the U.K. Directly involved in assessing the rare blood clot cases.
Does the Oxford/AstraZeneca vaccine cause blood clots?
There is now enough evidence to suggest that the Oxford/AstraZeneca vaccine is possibly the cause of rare blood clots and bleeding among a very small number of people who have received the vaccine. However, work is ongoing to definitively conclude this.
Sabine Straus, chair of the EMA's drug safety committee, concluded Wednesday that "these clotting disorders are very rare side effects of the vaccine," while June Raine, head of the U.K.'s MHRA, said the evidence suggests a "reasonably plausible link."
What's the evidence to date?
The EMA and MHRA have examined cases of unusual blood clots with low levels of blood platelets, small cell fragments that form clots and prevent bleeding.
As of April 4, the EU drug safety database had received a total of 169 cases of cerebral vein sinus thrombosis (CVST) — which occurs when a blood clot forms in one of the brain's veins, preventing blood from draining out of the brain — following vaccination. There had also been 53 cases of splanchnic vein thrombosis (SVT), an unusual manifestation of clots in one or more abdominal veins.
As of March 22, 18 of these cases were fatal. These cases were reported from among the 34 million people vaccinated so far with the Oxford/AstraZeneca jab in the European Economic Area, and the U.K.
What are the risk factors for these side effects?
So far, we don't know. "Based on the current available evidence, specific risk factors such as age, gender, or previous medical history of clotting disorders, have not been able to be confirmed, as these rare events are seen in all ages and in men and women," Emer Cooke, EMA chief, said on Wednesday.
Straus added that it was not possible to draw any conclusion on risk factors like age because of the different ways the vaccine is being used in different countries. The manufacturer, AstraZeneca, has been instructed by the EMA to carry out studies, and the regulator has also commissioned research to further investigate these side effects.
Why have countries stopped giving the vaccine to younger adults?
Several EU countries, including Germany, France and the Netherlands, have stopped giving the vaccine to younger adults. Without publishing the full reasoning from their vaccine committees, it's not clear exactly why. In Germany, by March 30, there were 31 suspected cases of blood clots in the brain, mostly in women aged between 20 and 63. Chancellor Angela Merkel announced the suspension of giving the Oxford/AstraZeneca jab to the under-60s, so it appears to be associated with the age range of the reported blood clot cases.
On April 7, the U.K.'s vaccine committee recommended offering the under-30s a different COVID-19 vaccine based on the benefit-risk profile for this age group. The committee said that when there is low prevalence of coronavirus, the potential benefit of averting serious illness from administering the vaccine in people aged under 30 does not outweigh the risk of harm from the jab. However, when coronavirus prevalence is high, the balance shifts, with the benefits outweighing the risks of harm in this group.
With coronavirus prevalence in the U.K. Now at about 1 case in 500 people — according to this week's latest REACT-1 study published by Imperial College London and Ipsos MORI — the committee has recommended a different vaccine for the under-30s.
What is happening in these rare cases?
Research to date suggests that an immune response is causing the rare blood clots. "Early evidence suggests that this constellation of symptoms is caused by an immune response against platelets, which allows the platelets to then lead to clotting in different parts of the body," said Munir Pirmohamed, chair of the U.K.'s Committee of Human Medicines.
This immune response leads to a condition similar to that seen in rare cases in patients treated with the anticoagulant heparin, called heparin-induced thrombocytopenia, according to Cooke at the EMA.
The cases that have been tested so far all have "a very odd antibody," said Beverly Hunt, professor of thrombosis and hemostasis at King's College London. It's an antibody to a molecule called platelet factor-4, which can also be a rare reaction to heparin.
When this happens, "you tend to activate platelets," she said, and by using up lots of platelets to form blood clots, the remaining circulating platelet count will fall. This is why you see clots and sometimes bleeding.
In addition, another marker called D-dimer, a small-protein breakdown product of clots, "is very high in these patients," she said, "showing that they've made clots." And some cases have also seen low levels of fibrinogen, the final protein involved in coagulation, also suggesting they are being used up in clotting.
Why is the vaccine linked to these rare blood clotting events?
Scientists have so far figured out what is happening in the blood, but not how the vaccine is causing these events.
This immune response could be caused by the vaccine or a prior COVID-19 infection, or something else, Pirmohamed said. "But what we don't have clearly is the link between the vaccine and how the immune response becomes activated against the platelets," he added.
Why is it important to find out why the vaccine causes this?
Scientists want to know what is causing these events so that they can identify if there are any risk factors. If we can understand the mechanisms "it might provide us with ways of being able to prevent this in the future," said Pirmohamed.
In addition, understanding how the vaccine may trigger this may allow scientists to modify the vaccine, so that it does not cause this particular adverse event in the future, he said.
The Oxford/AstraZeneca vaccine is an adenovirus viral vector jab. Is this side effect the same for all vaccines that use this technology?
So far, there's no evidence to suggest the Johnson & Johnson vaccine and the Sputnik V vaccine also have this side effect. However, data on these vaccines is limited, with Sputnik not approved for use in the EU and used only in a small number of people in EU countries that have bought it. And the J&J vaccine has not yet seen the mass rollout of the Oxford/AstraZeneca vaccine that has allowed the detection of very rare side effects.
"You could conceive that this is a [spike] protein related problem and that the mRNA vaccines are not doing it for some reason related to dose or expression," suggested Adam Finn, professor of pediatrics at the University of Bristol.
"I don't think we should be jumping to the conclusion that it's a viral vector problem specifically," he said. "I think that's one of several different possibilities."
Is prior COVID infection a risk factor?
It's something scientists are looking into. So far, about 25 percent of cases have shown a prior COVID-19 infection, but more data is coming on all of the cases. "Beyond that, we've not got analysis that tells us whether those cases are definitely different in any way or more severe," Finn said.
How can we prevent deaths from this side effect?
Doctors now know what to look out for if a patient presents with symptoms after vaccination, including severe headache, bruising, confusion, seizures, and chest or abdominal pain. And health care professionals have been updated.
"We feel fairly confident we're identifying the cases," said Hunt at King's College London. Treatment is similar to heparin-induced thrombosis and thrombocytopenia, which involves intravenous gamma globulin, "concentrated antibodies …. That block the effects of antibodies that are causing harm," she said.
She advised against anyone self-medicating with aspirin if they are worried about getting the jab.
Will under-30s be given the vaccine if there isn't an alternative in the U.K.?
That's unlikely to happen, according to Anthony Harnden, deputy chair of the U.K.'s Joint Committee on Vaccination and Immunisation, because the U.K. Isn't yet vaccinating that age bracket and more vaccines are coming. "We have good supplies of Pfizer, and Moderna's coming online, and there will be other vaccines which the government have ordered," he said.
How does the clotting risk compare with taking the contraceptive pill, and should we make this comparison?
According to Keir Shiels, a pediatrician at Great Ormond Street Hospital in London, the incidence of serious blood clots from the pill is far higher than the incidence of serious blood clots from the AstraZeneca vaccine.
"The combined oral contraceptive pill is probably the commonest cause of cerebral sinus thrombosis. So, it is a very good comparison," said Hunt.
"For the vast majority of people, if you want to reduce your risk of dying or getting hospitalized with a blood clot or any other illness if you're offered the AstraZeneca vaccine, you can reduce those risks by taking it," said Finn.
CORRECTION: This story was updated to clarify that several countries have stopped giving the Oxford/AstraZeneca vaccine to younger adults.
This article is part of POLITICO's premium policy service: Pro Health Care. From drug pricing, EMA, vaccines, pharma and more, our specialized journalists keep you on top of the topics driving the health care policy agenda. Email [email protected] for a complimentary trial.Is 'Long Vax Syndrome' A Rare Covid-19 Vaccine Side Effect? Here's What's Known
While the risk of postural orthostatic tachycardia syndrome (POTS) appears to be much higher after a ... [+] severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, there have been reports of people getting POTS after vaccination against Covid-19. (AP Photo/Kirsty Wigglesworth)
Copyright 2021 The Associated Press. All rights reservedLong Covid has long been a problem that has not gotten enough attention throughout the Covid-19 pandemic. And now researchers are longing to better understand "Long Vax Syndrome," a potential rare condition in which people's immune systems may be overreacting to the Covid-19 vaccine. It's being called "Long Vax" not because they've gotten vaccinated with a particularly long needle but because the symptoms have resembled long Covid. This has included headaches, major fatigue, blood pressure issues and abnormal heart rates that have lasted days, weeks and potentially even longer. The long and short it, though, is that the number of reported and confirmed "Long Vax" cases have still been far, far fewer than the number of reported and confirmed long Covid cases so far. Nevertheless, any potential real side effect of Covid-19 deserves a long, hard look by real scientists who really understand this area.
It's been tough to study this syndrome in large part because the number of reported cases has been so low to date and there hasn't exactly been an abundance of funding and support for such work. A pre-print posted on medRxiv back on May 17, 2022, did describe what happened to 23 patients who had reported seemingly nerve-related symptoms that began within a month of getting vaccinated against Covid-19. The patients ranged in age from 27 to 71 years with the median age being 40 years. All but two were women. None of them had any evidence of previous neurological illnesses.
However, after getting vaccinated, all 23 experienced funny sensations—funny as in pins and needles and not ha-ha funny—that were quite severe on their faces or limbs. Nearly, two-thirds (61%) had experienced POTS, as well as heat intolerance and irregular heartbeats. Now, in this case, POTS doesn't refer to the cookware as most people have experienced cookware at some point. Instead, POTS here stands for postural orthostatic tachycardia syndrome. This is a medicalese way of saying abnormal drops in blood pressure and lightheadedness (hence the word orthostatic) and increases in your heart rate (hence the word tachycardia) when going from you go from a lying position (meaning what you might do on a bed rather than what some politicians do a lot) to a standing one (hence the word postural).
Testing of 12 of these patients confirmed the presence of POTS in six of them. At the same time, the research team found that seven of the patients actually had reduced sweat production in their limbs. So what is the possible connection between POTS and not being able to sweat as much? Well, you could say the nerve of such findings.
POTS stands for postural orthostatic tachycardia syndrome. This is a medicalese way of saying ... [+] abnormal drops in blood pressure and lightheadedness (hence the word orthostatic) and increases in your heart rate (hence the word tachycardia) when going from you go from a lying position to a standing one. (Photo: Getty)
gettyThe research team led by Farinaz Safavi, M.D., Ph.D. And Avindra Nath, M.D., from the National Institute of Neurological Disorders and Stroke decided to put some skin in the game, so to speak, and take samples of skin from the lower legs of 16 of these patients. These biopsies revealed changes in and around the nerves of some of these patients, including 19% having abnormal swelling of their nerve axons. There was also quite a reaction in some cases. Some of these biopsies also showed collections of complement C4d—a chemical produced when the immune system reacts to something—in the cells lining blood vessels. All in all, over half (52%) of the patients had objective evidence of what's called small-fiber peripheral neuropathy.
So, it looked like the immune system may have been generating a reaction against nerve cells in the patients' bodies, causing inflammation. When you have an immune system reaction and inflammation, one general way is to give corticosteroids. Corticosteroids is sort of like the song "Don't Stop Believing" by Journey. They can be overused but can make you feel better regardless of the issue.
Eventually, 12 of these patients received oral corticosteroids treatment with seven experiencing either complete or near-complete improvement of their symptoms over the course of two weeks. By comparison, only one of the 11 patients who did not receive immunotherapy experienced full recovery from their symptoms at the 12-week mark. Further down the road, five to nine months after they first experienced symptoms, three of those who hadn't yet recovered were given intravenous immunoglobulin. All three had resolution of their symptoms within two weeks
Keep in mind that the pre-print was uploaded quite a long time ago, long at least in Scaramucci time. That was back when Taco Bell was running out of their Mexican Pizza as opposed to all the shortages that are occurring these days. This study still hasn't been officially published in any respectable peer-reviewed scientific journal. So, of course, you've got to take any pre-print with a fanny pack of salt. Pre-prints are a bit like videos on YouTube. Anyone can upload a pre-print as long as they have Internet access and opposable thumbs, although a seal could potentially upload a pre-print as well, assuming that the keyboard were large enough.
Moreover, this was a case series and not a study with adequate controls for comparison. A case series such as this alone can't determine whether the observed symptoms were actually due to the vaccine versus some other coincidence. Remember science is not about simply "casing" the joint, so to speak. While a case series can bring attention to something that may merit further investigation, it cannot determine cause-and-effect. Additionally, one study is never enough. Before any stronger conclusions can be drawn, you've got to conduct other types of scientific studies and see what the collective evidence shows.
Nevertheless, this pre-print hasn't been the only report of POTS and various pangs after Covid-19 vaccination. If you are curious, there was that case report published on May 4, 2021 in the journal Cureus of a 42-year-old man developing POTS after getting an Covid-19 mRNA vaccine. There was also that study published on December 4, 2o22, in Nature Cardiovascular Research co-authored by Alan C. Kwan, MD, and Susan Cheng, MD, of the Smidt Heart Institute at Cedars Sinai Medical Center in Los Angeles, California. They analyzed over 280,000 Covid-19 vaccination records and over 12,000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection records from Cedars Sinai Medical Center sing a sequence-symmetry analysis in over 280,000 COVID-19 vaccination records. They found that patients were 33% more likely to have a POTS-related diagnosis after vaccination compared with before vaccination. However, their analysis revealed that patients were 435% more likely to have a POTS-related diagnosis after exposure to SARS-CoV-2 infection than after vaccination. This suggested that POTS seemed to be possibility after vaccination but really at a much, much lower rate than after SARS-CoV-2 infection.
All of this has prompted more real scientists to listen even more closely to anyone expressing nerve-related symptoms after vaccination against Covid-19. Akiko Iwasaki, PhD, a Sterling Professor of Immunobiology and Molecular, Cellular and Developmental Biology, and Harlan Krumholz, MD, SM, a Harold H. Hines, Jr. Professor of Medicine at Yale University are leading the Yale LISTEN Study. LISTEN stands for Listen to Immune, Symptom and Treatment Experiences Now, as opposed to some other day. The stated purpose of this LISTEN study is "to understand Long Covid, post-vaccine adverse events and the corresponding immune responses by collecting information about symptoms and medical history from participants who are members of a patient community, and by collecting blood and saliva samples from some participants."
It is important to listen to any person who may be experiencing unusual symptoms after Covid-19 vaccination. You can't let the noise from various anti-vaccination politicians, TV/podcast personalities, and anonymous social media accounts drown out any real concerns. No, there's no real evidence that Covid-19 vaccines can turn you into a giant magnet or a refrigerator door, as I've covered for Forbes. No, there's no real evidence that people are using Covid-19 vaccines for genocide or to inject microchips to track and control people. No, there's no real evidence that many athletes are dying suddenly because of Covid-19 vaccines.
But this "Long Vax" possibility may have some real legs and deserves more investigation. Again, at this point, it seems to be a rare occurrence, although the scientific literature is currently short on studies to tell the true incidence. And there's always the chance that some more people have been suffering in silence. Sure, the potential benefits of the Covid-19 vaccines still appear to way outweigh the risk of "Long Vax" and other possible side effects. After all, you don't want to say, better long Covid than long Vax. Sure, you don't want to inadvertently support the unfounded claims of anti-vaxxers looking to cause chaos. But this doesn't mean that long Vax doesn't deserve a much longer and much harder look. In short, vaccine advocates shouldn't get into a POTS calling the kettle black situation and deny something that data may be showing. It may be a waste of time listening to those pushing unfounded claims about Covid-19 vaccines, but it is important to listen to those who may be suffering real problems after Covid-19 vaccination.
J&J Coronavirus Vaccine Linked To Low Blood Platelet Cases: EU Regulator
Johnson & Johnson's single-shot COVID-19 vaccine is linked to cases of low blood-platelet counts, the European Medicines Agency said on Friday.
The regulator's drug safety committee, PRAC, said it reached the conclusion after assessing available evidence from scientific literature, as well as cases of suspected side effects reported to the drugmaker and to European and U.S. Regulators. It didn't note in its statement how many cases it had observed.
This specific condition, known as immune thrombocytopenia, occurs when the number of blood platelets — which are needed for clotting — falls because the immune system mistakenly attacks them.
The committee recommended updating the vaccine information to include immune thrombocytopenia as a possible side effect and warning health care staff and vaccine recipients of this risk.
In addition, the committee called for adding dizziness and tinnitus to the list of possible side effects after concluding that some reported cases are also linked to the vaccine.
Separately, PRAC has requested further data from AstraZeneca to assess whether its two-dose adenovirus vaccine is linked to cases of Guillain-Barré syndrome, a rare immune disorder causing nerve inflammation, pain and difficulty walking.
At its last meeting, the committee recommended warning medics and recipients to be aware of this disease, but it has requested further data from the drugmaker "to clarify whether further updates to the product information and the risk management plan are necessary."
