British scientists have reported new discoveries into the development of vaccine-induced immune thrombocytopenia and thrombosis, also known as VITT.
The protein secreted by platelets, Platelet factor 4 (PF4), is known to be involved in this rare side-effect of vaccines, such as those against the SARS-CoV-2 virus. Antibodies that stick to PF4 combine with PF4, activating platelets and white blood cells. However, the precise mechanism of how this activation happened was not known.
The team of scientists, from the University of Birmingham, found that PF4 binds to, and activates, a thrombopoietin receptor on platelets called c-Mpl. This causes platelet aggregation by activating the proteins JAK2, STAT3 and STAT5.
In further tests, the scientists found that inhibiting a JAK2 pathway, using the drug ruxolitinib, which is a treatment for some types of blood cancer, can hold back platelet aggregation.
The findings were published in Blood.
Dr Pip Nicolson, who co-led the study with Dr Samantha Montague, said: “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.”
Dr Richard Buka, one of the joint first authors of the paper, added: “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.”
Buka RJ, Montague SJ, Moran LA, Martin EM, Slater A, Watson SP, Nicolson PLR. (2023) “PF4 activates the c-Mpl-Jak2 pathway in platelets.” Blood, doi: 10.1182/blood.2023020872
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