AstraZeneca : Et si les thromboses étaient causées par l

Needle in a blood vessel? The formation of blood clots blocking the blood flow a few days after injecting a dose of AstraZeneca vaccine in some people could be due to improper administration: the vaccine was injected into a vein rather than into the tissue. shoulder muscle. This is the hypothesis proposed by the group of researchers and doctors “On the side of science”, based on the scientific literature and developed in an article published on Thursday, March 25.

As a reminder, the National Medicines Safety Agency (ANSM) has confirmed the existence of a risk « rare » of atypical thrombosis associated with the AstraZeneca vaccine, in a press release dated Friday, March 26, stressing, however, that the benefit / risk balance remained « favorable ». Have thus been declared in France “Nine cases of thrombosis of the large veins [les plus graves, ndlr], atypical in terms of their location (mostly cerebral, but also digestive), which may be associated with thrombocytopenia or coagulation disorders, including two deaths ”. Most thromboses are treatable with an anticoagulant, although the most severe cases can lead to neurological damage or even death, for example by blocking the veins in the brain (cerebral thrombosis).

The Haute Autorité de Santé has also recommended that the AstraZeneca vaccine be reserved for people aged 55 and over, insofar as “The European Medicines Agency (EMA) has identified a possible increased risk of cases of disseminated intravascular coagulation (DIC) and cerebral venous thrombosis (CVT) in people under the age of 55”, according to the press release dated March 19.

Accidental passage into the blood and immune cascade

Several clues push the collective “On the side of science” to indict the intravenous passage as responsible for an increased risk of thrombosis. The central hypothesis is that this administration error would cause an autoimmune reaction, leading to the formation of blood clots. If the injection is intravenous, the first cells to be detected by the virus are mainly endothelial cells (those that line the blood vessels). “However, by associating with “héparanes sulfates“- cells which are located on the surface of endothelial cells – the virus could elicit an immune response against certain proteins in the “self“; those which are, at that time, in direct contact with the adenovirus”, explains Éric Billy, researcher in immunology and leader of the collective, who specifies “To have worked with adenovirus”.

And for good reason: according to a study published in the journal Blood in October 2020, the Spike protein of SARS-CoV-2 acts as an activator of the immune system and can induce an immune cascade, leading to thrombosis. “These antibodies will then in turn induce, by cascade, an activation of the blood platelets, to the point of generating a specific thrombocytopenia … that is to say a fall of these same platelets, limiting the capacity of coagulation in your blood”, continues the researcher.

Abnormal activation of a defense mechanism

Other parameters, with different levels of contribution, could associate this increased risk of thrombosis with intravenous injection, like the NET defense mechanism (Neutrophil extracellular traps). “In neutrophils [des globules blancs, ndlr], there is an innate defense mechanism (NET) which, like a net dropped in the body in the blood, aims to catch viruses ”, illustrates Mr. Billy. Problem (highlighted by several studies): in the case of SARS-CoV-2, this mechanism worsens the thrombotic elements in people with severe forms of Covid-19. The accidental injection of the vaccine into a vein could again explain the occurrence of thrombosis by abnormal activation of NET.

Finally, ” direct injection of adenoviruses into the blood would induce an innate and adaptive immune response, activation of neutrophils and release of NET. Then the formation of thrombus would define the severity of the thromboses ”, says Billy.

Adaptive immune response

The time interval between the injection of the AstraZeneca vaccine and the onset of thrombocytopenia – between four and fourteen days – also supports the hypothesis of an immune response resulting from intravenous passage. “The antibody immune response is roughly seven to ten days, which correlates well with the adaptive immune response that we have described in the case of the immune cascade.”, Eric Billy says.

If it was a question of toxicity due to the quantity of product injected, the pathology would appear much more quickly. ” In the publications on cytotoxicity identified by the direct injection of a large quantity of adenovirus, the animals die within hours or even minutes following the injection, adds Éric Billy. This is then an immediate toxicity. “

The article published by the collective indicates that the dose of adenovirus present in an injection of AstraZeneca vaccine (in number of viral particles per kg) is “35,000 times lower” to that used to obtain a toxic effect in mice. “Of course by typing “adenovirus“, “toxicity”, you will find articles in the scientific literature, many conspiracy theories are circulating on this subject on social networks … points to the immunologist. But the amounts of viruses have nothing to do with it! “

Favorable factors

It remains to be seen why cases of atypical thrombosis have overwhelmingly affected women aged 20 to 55, which the hypothesis of accidental intravenous injection alone does not explain. “Taking contraceptive pills (third and fourth generations) and smoking, which create the risk of thrombosis, could explain the frequency – beyond what is expected in a population – in women of a certain class of ‘age “, enlightens Corinne Depagne, pulmonologist and member of the collective “On the side of science”.

Risk factors, linked to gender and age, would thus be added to the discordant immune reaction, garnered by an accidental intravenous injection.

Rare accidental injection

Should we then fear an administration error during our vaccination? “No, stinging in vessels really happens very rarely!” “, reassures Ms. Depagne. There is also, normally, a control procedure so that the clinician can ensure that the needle is in the muscle tissue before injecting the dose of vaccine. “Historically, we have to make a blood call, that is to say we prick, then suck a little into our syringe to check that there is no blood coming back up and that we are not in. a vessel “, details Corinne Depagne.

According to the group, this protocol would be a simple way to overcome this potential accidental intravascular injection. « Or, “the absence of blood return“is not recommended today by the Ministry of Health for the AstraZeneca vaccine … We are not sure on what basis this decision was taken”, wonders the researcher in immunology.

In a report dated March 18, a pharmacovigilance team from the Danish Statens Serum Institute Moreover, recommends that the personnel responsible for vaccination draw a light suction on the plunger before administering the serum, thus making the same hypothesis as that supported by the French collective.

“We don’t claim to have THE solution. But considering that the incidence is still very low, that the products have been re-analyzed several times and that there is no batch specifically implicated, the trail of an accidental intravenous injection must be explored ”, concludes Eric Billy. “It is all of these hypotheses that would lead to an increased thrombotic risk … insists Corinne Depagne. But these are leads… for the time being, we don’t know! “ It is up to the scientific community to seek the needle in a bundle of hypotheses and uncertainties.


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