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New evidence has emerged today linking vaccines for COVID-19 to extremely rare cases of people developing blood clots and low platelets within weeks of vaccination.
A team of researchers in the UK conducted an in-depth study of 22 patients who developed severe blood clots along with a drop in platelet count after receiving a dose of the AstraZeneca vaccine, now called Vaxzevria. They also tested one patient who had clinical signs of a decrease in platelet count after vaccination. Nearly all patients – 22 of 23 – tested positive for unusual antibodies to platelet factor 4, a signaling protein that helps the body coordinate blood clotting.
The presence of the antibodies suggests that the vaccines somehow trigger an autoimmune attack that causes large clots that then reduce the supply of platelets in the blood.
The study and an editorial on the cases are published in the New England Journal of Medicine
This is at least the third study describing the presence of these antibodies in patients with blood clots and low platelets after vaccination, and doctors say the new evidence suggests doctors should remain vigilant for this new syndrome in anyone experiencing blood clot symptoms, where then also in the body, not just the brain.
James Zehnder, MD, director of the coagulation laboratory at Stanford University School of Medicine in California, said the growing evidence pointing to an “maladjusted immune response” was quite remarkable. He was not involved in the investigation.
Zehnder says that why this syndrome, which appears to be a type of autoimmune attack on a blood signal protein, develops in a small number of people after receiving the anticoagulant heparin or a vaccine against COVID-19 is still a great mystery.
He says that while the catastrophic cases of large blood clots in areas of the brain where doctors usually don’t see them, he wonders if other less obvious cases go unnoticed.
“Then the question is, you know, how much more of this is happening in a more subtle way? And so I don’t think its true magnitude is known,” he says, pointing out that it will be important in the coming weeks. and months to find out whether certain groups of people are at higher risk than others, such as young women. “There are now many more questions than answers,” he says.
Main symptoms to watch out for
The symptoms to watch for include shortness of breath, headache, dizziness, muscle weakness or abdominal pain, back pain or nausea and vomiting in anyone who is within 3 weeks of their vaccination, including men.
People who have not been vaccinated can also develop these types of blood clots called cerebral venous sinus thrombosis. These cases – whether they happen after a vaccination or not – are extremely rare. According to Peter Marks of the U.S. Food and Drug Administration, there are an average of two to fourteen cases each year of these blood clots in blood vessels that drain blood from the brain per million people.
Doctors say that in general, all vaccines authorized to protect people from the new coronavirus are extremely safe. In fact, the risk of developing a life-threatening blood clot is much higher with COVID than with a vaccine.
“The odds of this happening to you are about 1 to 100,000 to 1 in 1 million,” said John Wherry, PhD, director of the Institute for Immunology at the University of Pennsylvania in Philadelphia. “If you’re American, the chance of dying from COVID is 1 in 600,” Wherry continued, citing statistics on US COVID cases and deaths tracked by Johns Hopkins University.
In a presentation for the Centers for Disease Control and Prevention this week, representatives for vaccine manufacturer Johnson & Johnson said they found a 25-year-old man who developed a rare clot in his brain and low platelets during their clinical trial. When they went back and tested his stored blood, they found that he also had the telltale antibodies to platelet factor 4, making him the seventh known case associated with that vaccine in the United States. He has since recovered.
Researchers initially dismissed his case as unrelated to the vaccine because another study participant, a 24-year-old woman, also developed a similar blood clot in her brain, but she was in the placebo group. She had recently been given birth control pills, which increase a woman’s risk of blood clots and strokes, like the kind of pills she was suffering from.
An eighth case, possibly related to the Johnson & Johnson vaccine, is still under investigation in the United States.
Wherry said it is not surprising that these rare cases were not detected in the clinical trials, which involved tens of thousands of people. He said that very rare events sometimes only come to light when a drug or device is used in the millions, as the vaccines are now.
He said the fact that these events were detected at all means that security surveillance systems are working.
“We’re doing everything right,” he said. “It’s unfortunate and traumatic when it happens, but in terms of risk-benefit ratio we still have to put the numbers in perspective and now that we’ve noticed many of these events, we now have an idea of what to do when we see them , Wherry added.
UK cases
Of the 22 cases identified in the new UK study, 16 (70%) were under the age of 50 and 14 (61%) were women. They were all healthy before developing the rare clots. No one was on medications related to clotting or bleeding. Some came in with mild bruises and small red spots called petechiae, indicating subcutaneous bleeding.
This constellation of symptoms, severe clotting combined with a drop in platelet count, is not new. Doctors recognize it as a sign that someone is having a serious and rare reaction to the anticoagulant heparin. In patients taking heparin, it is called HIT, for heparin-induced thrombocytopenia.
Doctors examining the symptoms in the setting of the new COVID vaccines call it vaccine-induced thrombotic thrombocytopenia, or VITT.
The UK study authors found that a point-of-care test commonly used to detect HIT – the HemosIL AcuStar HIT IgG test – was often negative for patients with VITT. They say VITT should be confirmed by another kind of test, an ELISA or enzyme-linked immunosorbent test.
Patients with VITT also require a different type of treatment than would normally be given to a person with dangerous blood clots or bleeding. Administering platelets to stop bleeding, for example, can make the situation worse. Instead, they need IVIG treatment to mitigate the apparent autoimmune attack. Researchers say that until more is known, it is also wise to use anticoagulants other than heparin to treat clots.
Wherry says he is not surprised to see a few men affected, but the emerging picture so far suggests that women are at greater risk.
He says women are more prone to autoimmune diseases and are also more prone to blood clots because of the hormone estrogen.
“So it fits with this idea that this might be an indicator of autoimmune bias,” he said.
NEJM. Published online April 16, 2021. Full text, editorial
Several co-authors report receiving personal benefits from one or more of the following companies: Bayer, Bristol Myers Squibb, Daiichi Sankyo, Pfizer, Novartis, Octapharma, Sanofi, Sobi, Alexion, and Takeda. A co-author reports grants from Shire and Novartis; a co-author reports other financial relationships with GSK; and one co-author reports a patent-pending bacterial meningitis test based on a blood test.
Wherry reports consulting engagements with and / or is a scientific advisor to Merck, Roche, Pieris, Elstar and Surface Oncology. He has a patent license agreement for the PD1 pathway with Roche / Genentech and is one of the founders of Arsenal Biosciences.
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