Protein interaction causing rare but deadly vaccine-related clotting found

Credit: Mecder

A mechanism that led some patients to experience cases of deadly clotting following some types of Covid-19 vaccination has been identified in new research.

In a recent paper published in Blood, scientists from the University of Birmingham funded by the National Institute for Health and Care Research and the British Heart Foundation have been able to identify how deadly blood clots, in the disease known as Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT), occur.

Previous studies have shown that patients with VITT produce antibodies that stick to a protein called Platelet factor 4 (PF4) to create a large cluster of molecules called an immune complex. Following the development of a complex, platelets and cells of the immune system causing clotting and inflammation are activated, but the precise nature of what PF4 does in this event was unknown.

In this latest study the team used blood taken from healthy donors, as well as serum and plasma from patients with VITT, and have been able to learn for the first time how PF4 was directly involved in the activation of platelets and result in thrombotic events. By sticking to a receptor called c-Mpl on the surface of platelets, PF4 triggered the production of the small cells known to cause clotting.