Vascular occlusion, a phenomenon known as thrombosis, is a frequent clinical event throughout life. Approximately 100,000 cases appear in the European Union every month.
It has been known for a long time that there are numerous factors that predispose to the appearance of thrombosis in venous territories. For example, hormone replacement therapy in postmenopausal women or women treated for breast cancer and taking oral contraceptives (birth control pill) in young women. Immobilization, surgery, and certain autoimmune diseases, such as lupus erythematosus, also play a role.
Likewise, there are certain family situations, known as hereditary thrombophilias, that could facilitate the development of thrombosis in certain circumstances.
Finally, the history of previous thrombosis is also taken into account. These people are more prone to new thrombotic episodes.
Now also AstraZeneca
As we can see, there are a large number of circumstances that favor thrombosis. Furthermore, in recent weeks we have learned that the administration of the AstraZeneca vaccine carries a risk, although very low, of the appearance of a vascular occlusive phenomenon. One case is estimated for every one hundred thousand people who have received the first dose.
Therefore, lately it is common to answer questions related to the risk of getting the AstraZeneca vaccine. Should we be concerned if we are going to get vaccinated and have a predisposition or history of thrombosis?
This is an important issue that needs to be explained, although we are reiterative, because the factors responsible for the generation of a thrombus are very diverse and complicated. You cannot simplify or mix different situations.
In the vast majority of observed cases, thrombosis is preceded by a reduction in circulating platelets (thrombocytopenia). Platelets are very important elements in maintaining hemostatic balance. If there is a relevant decrease, the risk of bleeding increases and its activation can trigger and accelerate blood clotting and, therefore, the formation of the thrombus.
What is the mechanism behind the thrombi?
How can the mechanism behind the rare cases where thrombocytopenia and thrombosis have been seen after AstraZeneca vaccination can be explained?
The clinical observation of these patients showed a similarity with an also strange phenomenon that occurs in approximately 0.1% of patients receiving heparin. In them, from the first week of its administration, a variable reduction of platelets appears and, occasionally, it is accompanied by severe thrombosis. The condition was called heparin-induced thrombocytopenia (HIT).
In a study led by Dr. Andreas Greinacher, a researcher at the University of Greifswald (Germany), an interesting finding was made in this regard. In patients who suffered the complication, they detected an antibody against a platelet protein known as platelet factor 4.
This antibody was generated after the administration of heparin, which was capable of triggering its appearance by an autoimmunity mechanism. This condition could be diagnosed with the circulating detection of antibodies against platelet factor 4.
It was also shown that the interaction of the antibody, in addition to reducing the number of circulating platelets by increasing their destruction, was capable of activating them . This justified the appearance of thrombosis in both arterial and venous territory.
Similarities to Heparin Behavior
Until a few days ago, about 300 patients – of the 34 million who had received the AstraZeneca vaccine – presented a picture with certain similarities to patients with HIT. That is, thrombopenia and thrombosis, but without having previously been treated with heparin.
In these cases, the thrombosis was located mainly in cerebral and abdominal vessels. This new condition was called vaccine-induced thrombotic thrombocytopenia (VITT).
The clinical similarity led Dr. Greinacher himself and other groups to study and identify circulating antibodies against platelet factor 4, as well as platelet activation.
That suspicion has been buttressed by biophysical data obtained by another study (which is not yet peer-reviewed) from different German universities. These have shown that certain components of the vaccine complex with platelet factor 4.
Thus, they induce the appearance of autoantibodies, while other components of the vaccine itself promote an inflammatory reaction, favoring the appearance of these adverse effects.
Recently, the vaccine marketed by Janssen has also been linked to some cases of VITT. Both vaccines have been obtained by a recombinant procedure from the adenovirus vector that encodes the spike protein of the coronavirus.
Moderna and Pfizer vaccines follow a different procedure. The administration is messenger RNA (mRNA) and, although they have not been related to thrombosis, some cases of decreased platelet count have been described in some vaccinated people.
Combine vaccine and drugs, is it possible?
At this point, we can return to the question posed by many patients: if I am at risk of thrombosis or of suffering from thrombocytopenia, can I be vaccinated with Astrazeneca? Different international organizations such as the WHO and the scientific societies of hemostasis and thrombosis do not establish contraindications.
This decision is based on the fact that the possible adverse reaction of VITT is related to a special and very rare “hypersensitivity” to generate autoantibodies to platelet factor 4. The clinical history does not seem to be related to the appearance of the autoimmunity phenomenon described.
Many achievements are being made in a very limited space of time, but important issues remain to be clarified. For example, why does the VITT phenomenon appear in some people and not more generally? Will we have a test to help identify individual risk? Are there individual predisposing factors? Why are thrombi rare in patients with VITT?
The contribution of vaccines is, without a doubt, the fundamental element to defeat an unprecedented pandemic. There are already more than 400 million people in the world who have received different vaccines. Despite the rare adverse effects observed and its negative impact on some social sectors, we hope that the main objective is not limited: to get immunized against Sars-CoV-2 to recover global public health.
Vicente Vicente García, Professor of Hematology. Head of the Hematology Service of the Morales Meseguer University Hospital of Murcia, University of Murcia
This article was originally published on The Conversation. Read the original.
