Evidence is growing of a link between the Covid-19 vaccine and a deadly thrombosis – and theories are emerging as to why
@ 12 Apr 2021 17.34 EDT
Since rare but severe clotting was seen in some people following vaccination with AstraZeneca’s Covid-19 vaccine, researchers worldwide have been grappling to understand why the clotting syndrome, known as “thrombosis with thrombocytopenia” (clotting with a low platelet count), occurs.
Most cases of these clots occurred in veins in the brain (a condition called cerebral venous sinus thrombosis, or CVST), though some occurred in other veins, including those to the abdomen (splanchnic vein thrombosis). It has a high death rate.
Evidence is growing that the vaccine is causing this rare clotting syndrome. So what happens in those affected and, more importantly, why?
What do we know about this syndrome?
Platelets are cells that usually help to stop bleeding by clumping together to form a blood clot. In AstraZeneca vaccine recipients affected by this rare clotting syndrome, the number of platelets drops. A unique immune system reaction occurs involving the remaining platelets and white blood cells, and it is this reaction that makes the blood more clumpy, leading to clotting.
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The condition is very similar to another relatively rare but serious clotting condition caused by the use of a blood thinner called heparin. In both heparin use and administration of the AstraZeneca vaccine, the rare clotting disorder appears within two weeks, usually between day four and 20.
In those affected after being given heparin, the immune system makes antibodies to a complex of heparin and a protein called “platelet factor 4”, triggering this dangerous clotting. Those affected by the syndrome after receiving the AstraZeneca vaccine also have the same complex, with antibodies to platelet factor 4 in their plasma.
What’s causing this clotting?
Dr Jose Perdomo, a senior research officer in the haematology research unit at the University of New South Wales St George and Sutherland clinical school, said: “We know what’s happening, but the ‘why’ is not known.”
He said much is still unknown about why heparin-induced thrombocytopenia occurs, and that condition was first reported in the 60s. The exact mechanism causing the vaccine-induced thrombosis with thrombocytopenia may never be known, he said.But there are some theories.“One is that some people are already predisposed to this condition because of previous bacterial or viral infections,” Perdomo said.That’s because infections can lead the body to produce what is called cell-free DNA, which is basically extracellular DNA from dying cells in the blood (though cell-free DNA can also derive from normal cells).“That DNA somehow behaves like heparin – that the molecule, in this case DNA, can form complexes with the protein called platelet factor 4,” Perdomo said. “That complex is the one that gives rise to antibodies which see this complex as an invading bacteria. Once that complex is there, you have all these reactions including the activation of clotting for example.”Perdoma said one theory as to why the vaccine is triggering that antibody response against platelet factor 4 is that the AstraZeneca vaccine has DNA in it. “So that DNA in some people can get into the circulation and trigger these same complexes,” he said. “But that is just speculation and hasn’t been shown to be the case yet.”The other theory is that there may be some people predisposed to developing inflammation from the vaccine. That inflammation will lead to the production of cell-free DNA, and then the formation of the immune complex that leads to clotting.“What we know is the final complex is the same. That is, antibodies are being produced against platelet factor 4. And that complex is what activates platelets and other blood cells to form clots,” Perdoma said.