Scientists in Germany say they’ve worked out the two-step mechanism by which the AstraZeneca vaccine causes rare but devastating blood clots that gobble up the body’s supply of platelets. said Andreas Greinacher, MD, head of the Institute of Immunology and Transfusion Medicine, University Hospital Greifswald, Germany, who was among the first scientists in the world to link the rare clots to antibodies against a key protein in platelets. “This is, in my opinion, rock-solid evidence,” he said in a “This is what scientists usually think is confirmatory evidence,” call with reporters hours after publishing his study (read below) as a preprint ahead of peer review on the Research Square server. Greinacher said that he believes the mechanism linking the vaccine with the rare clotting reactions is likely to apply to other vaccines that also use adenoviruses to ferry instructions for making the virus’s spike protein into cells. In his new study, Greinacher and colleagues describe a series of events that has to happen in the body before the vaccines create these large clots. He explained that while everyone has the basic immune machinery that leads to the unusual clots, it is almost always kept in balance. The body uses a series of checks to prevent any step in the process from getting out of control. 2 Step Process how AstraZeneca Vaccine causes Blood Clots First Step In the first step, the adenovirus shell in the vaccine, along with proteins from the cells where the vaccine is grown, come into contact with platelets from the blood. Platelets are best known as colorless cell fragments that rush to the site of an infection or injury, helping the blood congeal to stop bleeding; they also play a key role in the body’s immune response. When activated, they surround invaders like bacteria and change shape to release chemical signals they store in granules. When platelets are activated en masse, as can happen rarely after a person takes the blood thinner heparin or gets the AstraZenecaAstraZeneca vaccine, they release a flood of these signals, Greinacher explained. These blaring signals recruit an ancient and hard-to-control branch of the immune response. “Imagine this is like a dragon in the cave who was sleeping for a long time [but] which now got alerted by someone’s throwing a stone on it,” he said. The chemical signals awaken B-cells that then produce massive amounts of antibodies against the platelet factor 4 protein, which helps coordinate blood clotting. The body erroneously thinks it is reacting to massive amounts of pathogens in the body, so the immune system overshoots.The antibodies bind the platelets, the platelets recruit white blood cells, and “then the whole thing is exploding,” he said. Second Step The second key step in these reactions is caused by EDTA, a calcium-binding agent and stabilizer that is added to the AstraZeneca vaccine. EDTA opens junctions between cells that form the walls of blood vessels, causing them to become leaky. This allows the giant complexes formed by proteins and platelets to enter the blood circulation, where they — on very rare occasions — trigger that body-wide alarm. But he said he was not a vaccine developer and didn’t know how important it might be to its formulation.e noted that women might be slightly more susceptible because of hormones and because women are more likely to develop autoimmune diseases, but that the risk was probably more balanced between men and women than it first seemed.