The European Medicines Agency (EMA) has just updated its report on AstraZeneca’s vaccine against Covid-19. The EMA has established “a possible link with very rare cases of unusual blood clots with low blood platelets”, specifying that the balance “benefits-risks” of vaccination still remains largely positive. The study committee conducted an in-depth analysis of 62 cases of cerebral venous thrombosis and 24 cases of splanchnic venous thrombosis, 18 of which were fatal. In recent weeks, many countries, including France, have temporarily suspended vaccination before seeing more clearly. If these cases remain extremely rare, they nevertheless deserve to be explained. Several research teams are trying to pinpoint the mechanism that leads to the occurrence of these cerebral thromboses. A very rare location, since the majority of thromboses affect the arteries and not the brain. Another surprising parameter: these thromboses are associated with a decrease in platelets in the blood, whereas it should be the reverse: more fluid blood promotes hemorrhages.
An error during the injection?
In an attempt to explain these thromboses, these blood clots that clog a vein, the collective On the side of Science suggests that this reaction could be due to a problem related to the injection at the time of the bite: the failed injection. would pass the contents of the syringe directly into the blood. The adenovirus synthesizing the S protein in the blood would generate an overly strong immune reaction, which would lead to coagulation problems and thrombosis. A hypothesis “surprising” for Pr Stéphane Zuily, professor of vascular medicine at the Nancy CHRU. “The blood vessels under the skin are made up only of capillaries, small tubes the size of a hair, even smaller than a needle. Nothing prevents damage to a capillary at the time of injection and the product passes through the capillary. So there might be a local reaction. But that does not explain why thrombosis takes place in the head when injecting in the arm. Also, when injecting the product , the spike protein (present on the surface of the coronavirus, editor’s note) is encapsulated in lipid beads. It would have to come out of the capsule to diffuse into the capillary and then join the circulation more widely. But the capsule is made to diffuse in the muscle, not in the blood. ” These are all factors that leave specialists perplexed. “Anyone can miss their injection, but this is not the most convincing hypothesis.“, replies Dr Nicolas Gendron, doctor in the hematology department of the Georges-Pompidou European Hospital in Paris.
An antibody directed against patients’ platelets
Another lead emerges from Germany, where the team of Professor Andreas Greinacher, from the University of Greifswald, a leading specialist in his field, published an article on the link between the AstraZeneca vaccination and the occurrence of thromboses . In its analysis, the team examines the case of nine patients (aged 22 to 49) who presented with thrombosis between 4 and 16 days after vaccination. Among them, seven patients presented with cerebral thrombosis and four died. Prof. Greinacher describes an inappropriate immune system reaction to the vaccine and compares it to a pathology of which he is a great specialist: heparin-induced thrombocytopenia (TIH).
Heparin is a drug that has been used for over a hundred years, the main property of which is to prevent blood from clotting. In this, it is considered to treat thrombosis due to Covid-19 (since by thinning the blood, it prevents the formation of blood clots). However, in the reactions observed by the German team, some patients would present an allergy to heparin. On contact with this substance, the body would create anti-PF4 antibodies all over the platelet membrane. When the antibodies attach themselves to it, the platelets are activated. They all aggregate together. Hanging together, they form large clumps, which will cause a blood clot. In blood tests, the results show a low level of platelets. In reality, the patient has none the less; only, there are not many free left because many of them are agglutinated in the blood cluster. “It is an abnormal and serious reaction that we know from our fourth year of medicine“‘, explains Professor Zuily.
How is it that some patients are allergic to heparin without ever having been exposed to it? “There are different types of allergies. Some come with exposure to a factor, such as hazelnuts or peanuts. For others, they are immediate allergies that can be had without prior exposure.“For Prof. Greinacher from the Greifswald team, it would happen much the same in patients who received the vaccine, except that this time heparin does not come into play but the AstraZeneca vaccine is based on the technique of attenuated adenovirus (which uses a virus that is alive but made harmless to humans, to carry a specific part of the DNA of another virus). “In the same way, the system feels attacked, it jumps on the patient’s endothelial cells and causes a real blow of intravascular firedamp. Everything gets carried away and the patient ends up in thrombosis“, explains Pr Elalamy, head of the hematology service at Tenon hospital in Paris.
Detect and then treat this extremely rare reaction
A theory “quite convincing“for Dr Nicolas Gendron of the Georhes-Pompidou European Hospital in Paris. Especially since the study completes its work with a test carried out on patients, in whom anti-PF4 antibodies were found in four of the patients. “Any laboratory can do this test to detect this new antigen. So in case of suspicion, we could also use it in our laboratories. We don’t know why this happens but we know how to diagnose it now, which is a real breakthrough.“Treatment can even stop the progression of blood clotting.”Immunoglobulins can be given intravenously. They are really well tolerated and make it possible to counter the antibodies produced by the body. So no chain reaction“, specifies Professor Elalamy.
It remains to be seen why thrombosis occurs in the brain. “The way the veins in the brain, their endothelium, are formed would be different compared to other places in the body, including the lungs. This could be part of the answer. Added to this, there are certain so-called “unusual” thromboses linked to heparin-induced thrombocytopenia. It could correspond to it“, suggests Professor Zuily.
The benefit of vaccination is vastly greater than the risk
The three specialists specify that this reaction remains extremely rare and that it remains of the order of 1 case per 100,000 people, or even 1 case in 250,000 according to calculations. The benefit of being vaccinated to protect yourself from Covid-19 therefore remains immensely greater than the risk. “Vaccinating makes it possible to protect and to offer a sustainable long-term solution. Today this protection is essential”, recalls Professor Elalamy. After vaccination, monitor the injection site for any reaction. In case of pain in the arm which persists after three days, an arm which swells, severe pain in the head or in the leg, then the patient can consult. Health care practitioners will see with a simple blood test whether a “vascular storm“is in progress or not and an appropriate response will be offered.