Genetic trigger identified for vaccine-related blood clots

An international team reports a genetic mutation that can produce the antibody linked to rare vaccine-induced blood clots (VITT), and reversing that mutation removed clotting potential in lab tests; the study appears in the New England Journal of Medicine.

Researchers say they have identified a genetic change that can create the antibody responsible for rare blood clots after certain COVID-19 vaccines. The finding was published in the New England Journal of Medicine and builds on research by teams in Canada, Germany and Australia. The condition, called vaccine-induced immune thrombocytopenia and thrombosis (VITT), was seen mainly after adenovirus-based vaccines such as those developed by AstraZeneca and Johnson & Johnson. The discovery ties together earlier structural studies of the antibody and laboratory tests that removed clotting potential when the mutation was reversed. Key points: - The study identifies a specific antibody genetic sequence and shows how a single mutation in immune cells can convert a benign response to one that binds platelet factor 4 and triggers VITT. - In Canada about 2.3 million people received at least one dose of the AstraZeneca vaccine and 56 cases of VITT were reported by July 2021, including six deaths, translating to roughly one case per 41,000 doses. - Laboratory work showed that reversing the mutation removed clotting activity in tests using mice engineered to model the human immune system. - The researchers note it is not currently possible to screen people ahead of time because the mutation arises in immune cells while they are producing antibodies, though the finding may inform future vaccine design. Summary: The research explains a plausible mechanism for VITT and links it to antibodies produced in response to an adenovirus protein, while showing that the mutation is functionally reversible in lab models. The work may guide how adenovirus-based vaccines are engineered in the future and could offer insight into other rare immune disorders. Undetermined at this time.