Researchers have identified the mechanism that leads to blood clotting in some patients after the COVID-19 vaccine, according to a study published in the scientific journal Blood. This discovery means researchers and doctors can develop ways to block thrombosis from developing after vaccination.
A team of scientists from the University of Birmingham, UK, have identified how deadly blood clots occur. This is known as Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT).
Previous work has shown that patients with VITT produce antibodies that bind to a protein called Platelet factor 4 (PF4), creating a large cluster of molecules called an immune complex. The development of this complex activates immune cells, which in turn cause inflammation and clotting. However, the precise nature of this mechanism is unknown.
In this study, the researchers used blood from healthy participants and patients with VITT to understand how PF4 is directly involved in the activation of platelets and resulting blood clots. It turns out PF4 can bind to a receptor called c-Mpl and trigger the clotting.
“The major advances seen in vaccine development during the global Covid-19 pandemic were thrown into sharp relief following the tragic, rare cases of vaccine-induced immune thrombosis. While there were alternative vaccines available to continue to provide protection against the coronavirus in some countries around the world, understanding the mechanisms behind these cases is critical to ensuring that the technology for delivering vaccines can be used with confidence in the future,” said Dr. Pip Nicolson, Associate Clinical Professor in Cardiovascular Medicine at the University of Birmingham and senior author of the study.
“As well as identifying a new way in which platelets are being activated in a potentially deadly manner in VITT, our research has also been able to find how this mechanism may lead to new drugs to protect against blood clots in VITT and blood clots in general,” added Dr. Richard Buka, Research Fellow in the Institute of Cardiovascular Sciences and co-lead author.
The researchers used ruxolitinib, a drug used to treat some types of blood cancer, to block the receptor responding to PF4 after the vaccine. Although they note that this drug is unsuitable for use in VITT patients, the team still identified that blocking the pathway using ruxolitinib slowed down clotting, demonstrating a potential future way to protect patients.
“It is gratifying that we have been able to identify a new, important biological mechanism through trying to thoroughly understand a new disease. This work helps us to understand more fundamental things about how blood clots form and may also be relevant in other related diseases that are more common,” said Dr. Samantha Montague, Research Fellow in the Institute of Cardiovascular Sciences at the University of Birmingham and co-lead author of the paper. “Our ongoing research funded by the British Heart Foundation is looking at how we can identify patients who may develop VITT, with a view that future vaccine programmes around the world can be delivered while understanding and managing the potential risk for those few at greatest risk.”
Buka RJ, Montague SJ, Moran LA, Martin EM, Slater A, Watson SP, Nicolson PLR. PF4 activates the c-Mpl-Jak2 pathway in platelets. Blood. 2023 Oct 26:blood.2023020872. doi: 10.1182/blood.2023020872.