European medical regulators concluded on Wednesday that there is a strong link between AstraZeneca’s COVID-19 vaccine and life-threatening conditions related to the unusual combination of blood clots and low platelets.
As such, the conditions should be listed as “very rare side effects” of the vaccine, according to the European Medicines Agency, a regulatory agency of the European Union.
The conclusion was based on the EMA’s in-depth review of 86 blood clotting events among approximately 25 million people vaccinated with the AstraZeneca vaccine in Europe and the UK. Of the 86 blood clotting events, 18 people died. Most – but not all – cases occurred in women under the age of 60.
The events reviewed by the EMA included 62 cases of cerebral sinus vein thrombosis (CVST), a rare form of stroke in which a clot prevents blood from draining from the brain. The remaining 24 cases were splanchnic venous thrombosis, which involves blood clots in the veins that drain blood from the abdomen.
Aside from the 86 cases examined, the EMA estimated that there is a report of one case of the side effect in 100,000 people vaccinated.
Curiously, the clotting events were accompanied by low levels of platelets, the blood cell fragments that stick together to form clots. Typically, low platelets lead to more bleeding, not clotting. Regulators noted that this unusual combination resembles a condition called heparin-induced thrombocytopenia, or HIT. In rare cases, patients receiving heparin – an anticoagulant – see a drop in their platelets, but still go into a hyper-clotting state, which can lead to widespread clotting and death.
HIT is caused by an abnormal immune response. In a response to heparin that is not fully understood, some patients’ immune systems produce antibodies that attack a common platelet protein called Platelet Factor 4, or PF4. This, in turn, leads to platelet activation and particle pro-coagulation, leading to HIT.
Some researchers suspect that the blood clotting events associated with AstraZeneca’s vaccine may also be due to a similar, violent immune response – and that it may be treatable. Extremely preliminary data – posted online but not yet published in a journal or peer-reviewed – indicates that the rare condition can be treated in some vaccinees with non-heparin anti-caking agents and with a high dose of immunoglobulin, which has been shown to inhibit platelets . activation in HIT patients.
In its announcement Wednesday, the EMA noted that recognizing the early signs of blood clots and low platelets is critical, and getting specialized treatment quickly can prevent serious consequences.
The EMA noted that recently vaccinated people should watch for:
- shortness of breath
- swelling in your leg
- persistent stomach pain
- neurological symptoms, including severe and persistent headache or blurred vision
- small spots of blood under the skin outside the injection site
As seen in people who develop HIT after heparin, blood clotting events and low platelet counts in vaccinees usually develop within two weeks of receiving their first dose.
Although the EMA has reinforced the link between the clots and the AstraZeneca vaccine, it still recommends using the vaccine. “The reported combination of blood clots and low platelets is very rare,” the agency noted, “and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.”
The conclusion follows weeks of tragedy surrounding the vaccine, in which more than a dozen countries that had already approved use of the vaccine abruptly stopped vaccinations over concerns about the blood clots – then resumed use over concerns about the spread of COVID. 19.
Along with the EMA, the World Health Organization continues to make strong claims that the benefits of the AstraZeneca vaccine’s effectiveness in preventing deadly COVID-19 infections far outweigh the risks of extremely rare blood clotting disorders.
Nonetheless, last week Germany started restricting the use of the vaccine in people under the age of 60, the age group in which most, but not all, of the rare clotting events have occurred. And on Tuesday, the University of Oxford, which co-developed the vaccine with AstraZeneca, said it had paused a small UK trial of the vaccine in children and teens.
Meanwhile, AstraZeneca remained mired in communication problems. In the latest misstep, the company got into a highly unusual and disturbing argument with a panel of US experts overseeing the COVID-19 vaccine trial and data. The panel, dubbed the Data and Safety Monitoring Board, claimed that AstraZeneca picked out the results of the research data it released in a press release, potentially misleading the public as to the vaccine’s true effectiveness.
The company has defended its actions but has not yet submitted its data to the U.S. Food and Drug Administration to obtain an Emergency Use Authorization. Last week, Anthony Fauci, the top infectious disease expert, suggested that even if authorized, the US may not need the AstraZeneca vaccine as it will have adequate supplies of the three vaccines already in the US approved.
Problems for Johnson & Johnson
The new list of side effects in the EU will only make things more difficult for AstraZeneca. And it also likely casts a shadow over the Johnson & Johnson COVID-19 vaccine, which is approved in the US and elsewhere and uses the same design as AstraZeneca’s vaccine.
Both vaccines use an adenovirus vector. Adenoviruses are common viruses that can cause cold-like infections and other mild illnesses in humans. For the delivery of vaccines, they are designed so that they cannot multiply in cells or cause disease, but they can deliver the genetic code of a more dangerous germ to cells. In the case of the COVID-19 vaccines, the engineered adenoviruses provide the code for the SARS-CoV-2 spike protein, which adorns the outside of the virus particle. The spike protein is what SARS-CoV-2 uses to grab and enter human cells – and it’s a prime target for potent antibodies and other immune responses. Once the adenovirus vector provides the code for the peak, our cells can make their own versions of the protein and use them to train immune responses that recognize and destroy the SARS-CoV-2 virus.
One potential pitfall of adenovirus-based vaccines is that adenoviruses can also bind to platelets and cause problems. Some pre-pandemic data even suggests that adenoviruses can activate platelets and lead to low platelet counts. But the link between this and the vaccine and the mechanism that causes blood clotting in vaccinees needs much more data to understand.
Still, the side effects of AstraZeneca’s vaccine raise concerns about Johnson & Johnson’s. During the clinical trials of the Johnson & Johnson vaccine, there was an early sign of an increased risk of these blood clotting disorders in vaccinated people, Peter Arlett, head of data analytics at the EMA, said in a news conference Wednesday. But the link has never been confirmed, he added.
Of the approximately 4.5 million people who have received the Johnson & Johnson vaccine worldwide, three cases of blood clotting similar to those seen in people who received the AstraZeneca vaccine have been reported, Arlett said. These numbers are “extremely small,” he emphasized. “However, this is being closely monitored … I think it would be fair to say that this issue is closely monitored across all vaccines.”