Can the AstraZeneca vaccine cause blood clotting?
Recently, a few European countries stopped the use of Oxford-AstraZeneca COVID-19 vaccine due to the alleged connection between this vaccine and the creation of blood clots.
The connection is not confirmed but the suspension of the vaccination program raises an interesting question:
What would be the mechanism that connects this particular vaccine and blood clot formation?
The most likely explanation lies in a structure called the endothelial glycocalyx (which, for some reason, scientists just keep ignoring).
Endothelial glycocalyx (I will refer to it as eGC in this article ) is a layer of proteoglycans and glycoproteins that covers the luminal side of the blood vessels and creates a barrier between endothelial cells and blood components (Figure 1).
Since my last speculative article in early April of 2020, the connection between eGC and SARS-CoV-2 has been confirmed — It was interesting to write and learn about eGC from the sidelines and watch it being connected to the COVID-19 symptoms in real-time.
It is now known that the spike protein of the novel coronavirus binds both to the ACE2 cell receptor and to heparan sulphate (HS) as well.
Heparan sulphate (HS) is a part of the eGC structure.
HS is an important glycosaminoglycan ubiquitously expressed on cell surfaces, including the surfaces of the endothelial cells, where it plays a role in many different immune system-related processes.
When SARS-CoV-2 binds to the ACE2 receptors in the lung epithelial cells, a person may develop respiratory symptoms of COVID-19. On the other hand, if this virus binds to HS expressed on the endothelial cells, a person might develop vascular symptoms of COVID-19, which have been reported since the novel coronavirus outbreak.
Let's dig deeper — how does the interaction between HS and SARS-CoV-2 look like — a story of a dysfunctional relationship?
Once inside a human body, SARS-CoV-2 virus travels hopelessly across the bloodstream until it finds its vascular soulmate — heparan sulphate. They form a tight bond and travel together inside the endothelial cell — via the process called endocytosis or internalization. Like all toxic relationships, this love affair causes some destructive consequences:
- SARS-CoV-2 is now inside the endothelial cell and can cause vascular damage.
- The amount of heparan sulphate on the endothelial cell surface is lowered (you could say that HS lost its true self in this relationship).
What does lowering the amount of surface HS mean for the body?
The eGC is comprised of many different glycoproteins, proteoglycans and other supporting structures that have one thing in common — they are negatively charged. This net negative charge allows for the plasma proteins, such as albumin, to bind to the eGC. These kinds of interactions extend the length of the whole glycocalyx structure and form a steady protective barrier called the endothelial surface layer (Figure 1).
One of the functions of this surface layer is to prevent leukocytes and platelets adherence, rolling and migration into the endothelial cells and deeper structures.
This is where it gets interesting:
The Oxford AstraZeneca vaccine is made a bit differently than the others. It uses adenovirus-vectored technology, meaning that a version of adenovirus (that cannot harm humans) is used as a transporter of the SARS-CoV-2 spike protein.
The spike protein is a part of the SARS-CoV-2 that we need to show to our immune system in order for it to create defences for novel coronavirus.
Some research suggests that the adenoviruses bind to HS as well.
This kind of research is usually aimed towards developing cancer treatments, as the interactions between non-harmful adenoviruses and HS could be a way to deliver cancer therapy inside the cell, without damaging healthy parts of the body.
Putting it all together
Although the internalization of a complex between adenovirus and HS might seem ‘helpful’ at first, in the case of the COVID-19 vaccine — it might show signs of a dysfunctional relationship.
As I mentioned before, when a virus binds to the cell surface HS, the whole structure gets internalised, causing the endothelial surface layer to lose its firm structure and its balance with blood plasma proteins. In addition, the eGC loses a part of its negative charge.
The net negative charge and homeostasis with the plasma proteins was what kept the leukocytes and platelets from coming close to the endothelial cells (check out one of my earlier articles for more info).
Without surface HS, the leukocytes and platelets are now “free” to adhere to the endothelial cell and cause, guess what — blood clots.
If this is true, what could be done?
Unnecessary blood clot formation can lead to thrombosis. One of the treatments for this condition in acute settings is the injection of intravenous heparin, a heparan sulphate analogue molecule that exhibits similar properties. Perhaps the addition of heparin could be considered to prevent blood clot formation.
Also, there is some evidence of certain nutrients acting in a protective manner towards eGC, a nutritive cocktail would provide blood vessel support and could be easily administered adjacent to the vaccine — more research is needed in this area!
I don't want to discourage you from vaccinating, this is not an anti-vaxxer article — it is just my personal speculation and is not backed up by experiments. The fact that some adenoviruses bind to HS, does not mean that the Oxford AstraZeneca version does as well.
At this point in time, the benefits of vaccinating still outweigh the potential side effects.
If you are a researcher and this article helped you put some pieces of the puzzle together or if you find it incorrect, please let me know!
If you are as passioned about the endothelial glycocalyx as I am — I am open to collaboration!
