Scientists have identified a new underlying mechanism of platelet activation in vaccine-induced immune thrombocytopenia and thrombosis.
New research may explain why some individuals experience a rare and often fatal blood clotting disorder after receiving a COVID-19 vaccine. In a recent study published Oct. 26 in the peer-reviewed journal Blood, funded by the National Institute for Health and Care Research and the British Heart Foundation, scientists from the University of Birmingham, United Kingdom identified a new mechanism of platelet activation in vaccine-induced immune thrombocytopenia and thrombosis (VITT).
VITT is a clinical syndrome associated with COVID-19 vaccines that is characterized by thrombosis, or blood clots, at uncommon sites and mild to severe thrombocytopenia. Thrombocytopenia occurs when blood platelets are too low, resulting in excessive bleeding. VITT is similar to heparin-induced thrombocytopenia (HIT) but without prior exposure to the popular anticoagulant drug.
“Although VITT only emerged recently, the research that it has triggered is teaching us a lot about how the body works and how it can go wrong,” Richard Buka, co-lead author, and clinical research fellow at the University of Birmingham Institute of Cardiovascular Sciences, told The Epoch Times in an email.
“Our ability to work on VITT has allowed us to discover a new biological pathway—one that was unknown before. This might have relevance to lots of other fields of research, including clotting disorders more generally, and in understanding how the bone marrow makes platelets,” he added.
According to the study, people with VITT or HIT produce antibodies against a small chemokine protein released by activated platelets and form immune complexes—large clusters of molecules that activate platelets and cells of the immune system that cause clotting and inflammation.
“VITT is caused by a misguided immune response which is normally thought to protect us from infection. That immune response leads to strong antibodies against a molecule called platelet factor 4 (PF4),” Mr. Buka told The Epoch Times. “Antibodies and PF4 form large complexes which can then activate platelets and white blood cells, leading to inflammation and blood clots.”
Although scientists knew PF4 played a significant role in promoting blood coagulation and is involved in innate and adaptive immunity when platelets are activated in response to infections, the exact nature of how PF4 contributes to this process was previously unknown.
In the study, researchers collected blood samples from healthy volunteers after vaccination with AstraZeneca’s COVID-19 vaccine and nonvaccinated healthy donors to determine the role PF4 plays in activating platelets leading to thrombotic events.
Researchers found that PF4 binds to a receptor called c-Mpl on the surface of platelets, triggering small cells known to cause clotting. High concentrations of PF4 were shown to induce “robust platelet aggregation” through the c-Mpl thrombopoietin (TPO) receptor, and lower concentrations can increase the likelihood of platelet activation through the same pathway.
The TPO receptor is the chief regulator of megakaryocytes, which are responsible for producing blood platelets. Mr. Buka said he and the authors of the paper have been working on how platelets become activated in VITT.
“Previously, it was thought that the antibodies themselves activate platelets, but we have found a role for PF4 in this process. We discovered that PF4 can bind to a receptor on platelets and increase their activation—making clots more likely to form,” he said.
Knowing the role PF4 plays in VITT may open the door to better treatments for the condition, Mr. Buka added.
“We can block this process with a commonly used drug, ruxolitinib. It’s reasonable to think that this might be a good treatment for VITT, but we think that this is playing a more minor role in platelet activation. However, there are other drugs that we could use to reduce platelet activation, which in theory would be an ideal treatment,” Mr. Buka said.
The limitations of this study include its small sample size and the differing treatments received before participant samples were collected. Additionally, only a limited number of conditions were tested due to the limited sera available, and aggregation was measured only over 10 minutes instead of 30 minutes for those with VITT.
“I’d really like to pay tribute to the patients and their families with VITT who have, and continue to suffer,” Mr. Buka said. “We are privileged to work on these extremely rare blood samples, and we will continue to strive to understand as much as we possibly can about VITT.”
Blood Clotting Disorders Linked to AstraZeneca
European regulators in April 2021 first acknowledged a possible link between AstraZeneca’s COVID-19 vaccine and “very rare” blood clots after a review of 62 cases of cerebral venous sinus thrombosis (CVST) and 24 cases of splanchnic vein thrombosis were reported to the EU drug safety database EudraVigilance during the first few months of Europe’s vaccine rollout.
The UK’s vaccine regulator, the Medicines and Healthcare Products Regulatory Agency issued a press release in April 2021 acknowledging that evidence of a link between AstraZeneca’s vaccine and blood clots is strong but said more research was needed.
The European Medicines Agency (EMA)’s safety committee did not recommend restricting the use of the vaccine but did say cases of blood clotting after vaccination should be listed as a possible side effect. The EMA also said it was investigating several reports of blood clots in those who received the Johnson and Johnson (J&J) COVID-19 vaccine manufactured by Janssen.
Despite insistence by regulators that the “overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects,” more than 20 countries paused or suspended the use of AstraZeneca as a precautionary measure.
In June 2021, scientists from Norway, Germany, and the UK published papers in the New England Journal of Medicine on CVST with thrombocytopenia and anti-PF4 antibodies in individuals following vaccination with AstraZeneca, naming the new syndrome VITT.
CDC: Johnson & Johnson ‘Plausibly’ Linked to Blood Clots
Similar to AstraZeneca, the J&J COVID-19 vaccine used a modified adenovirus vector as opposed to the mRNA technology used in Moderna and Pfizer’s COVID-19 vaccines.
Federal agencies in April 2021 paused the J&J shot to investigate the vaccine’s possible link to potentially dangerous blood clots. In a joint statement issued by the U.S. Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA), the agencies said they were investigating six cases of blood clots in the United States in women between the ages of 18 and 48 who developed symptoms six to 13 days after vaccination.
During an April 23, 2021, meeting, the CDC’s vaccine advisors identified at least 15 women diagnosed with rare blood clots, including three who died following vaccination with J&J, and acknowledged the risk of experiencing blood clots was highest in women ages 30 to 39.
The CDC advisory safety committee said the link between blood clots and J&J’s COVID-19 vaccine was “plausible” but concluded the vaccine’s benefits still outweigh the risks. Three days later, the FDA amended its Emergency Use Authorization (EUA) for the J&J vaccine to reflect the risk of rare blood clots and said vaccinations could continue immediately. As the use of the J&J shot increased, so did reports of blood clotting disorders until the FDA revoked EUA for the shot in June 2023 at the manufacturer’s request—for unrelated reasons.
Blood Clotting Disorders Reported After mRNA Vaccination
Although VITT is only publicly associated with the administration of AstraZeneca’s COVID-19 vaccine and the J&J shot, thousands of blood clotting disorders have been reported to the CDC’s Vaccine Adverse Event Reporting System (VAERS) following vaccination with mRNA vaccines Pfizer and Moderna.
According to the CDC’s most recent VAERS data, between Dec. 14, 2020, and Sep. 29, 2023, there have been 48,673 reports of blood clotting disorders. Of those, 33,566 reports were attributed to Pfizer, and 11,113 reports were attributed to Moderna.
According to a CDC 2021 presentation, the CDC and FDA search VAERS daily for blood clotting disorders associated with vaccines, including rare thromboses (e.g., cerebral venous thrombosis), deep vein thrombosis, pulmonary thromboembolism, ischemic stroke, and myocardial infarction.
Using only the CDC’s inclusion criteria for blood clotting disorders, VAERS shows 19,880 cases of blood clotting disorders associated with COVID-19 vaccines, including 1,531 reports attributed to J&J, 13,748 reports attributed to Pfizer, and 4,589 cases attributed to Moderna.
As early as 2021, studies and case reports were being published on blood clotting disorders following vaccination with Pfizer and Moderna’s COVID-19 vaccines.
A study published in 2021 by Oxford University found the number of people who developed CVST blood clots after COVID-19 vaccination was about the same for Pfizer, Moderna, and AstraZeneca. According to the study, 4 in 1 million people experienced CVST during the two weeks following vaccination with the Pfizer or Moderna vaccine versus 5 in 1 million people for the AstraZeneca vaccine.
Although researchers noted a higher incidence of blood clots in those infected with SARS-CoV-2, the incidence of blood clots following vaccination was still much higher than the background incidence of 0.41—a signal that vaccines pose this specific risk.
A study published in February 2021 in the American Journal of Hematology examined thrombocytopenia following Pfizer and Moderna vaccination. After analyzing 20 case reports of patients who developed immune thrombocytopenia following vaccination, including 17 without preexisting thrombocytopenia, researchers could not exclude the possibility that Pfizer and Moderna’s vaccines have the potential to trigger the condition and recommended additional surveillance.