In-depth expository into Coronavirus Vaccine-Induced Thrombotic thrombocytopenia and associated side effects

It is no longer news that coronavirus vaccines comes with salient side effects . These side effects usually include Self limited symptoms like headache, fever, chills, body pain and rarely thrombosis.

This are usual normal symptoms associated with vaccination of any kind and it simply proves that the body is building protection CDC, 2021.

It is worth knowing that to date, approximately over 4.4 billion vaccine doses have been administered to individuals globally as an effort towards protection against Covid-19 infection, Syed Hassan Ahmed and colleagues, 2021. A more updated record from National public health agencies reveals that as of 23 December 2021, 8.85 billion doses of COVID‑19 vaccines have been administered worldwide.

A lot of rumours regarding the coronavirus vaccines abound but I won't bother bugging us about them, the most important thing is conveying verifiable facts and not rumours.

The thrombotic thrombocytopenia associated with coronavirus vaccine is not a rumour. These adverse effect though is not common with everyone, reason being that, not all that receive coronavirus vaccines experience adverse effects.

Thrombophilia

This post is in no way intended to scare the reader, rather it is aimed at enlightening the general public about the subtle adverse effects associated with coronavirus vaccines after their administration. Increasing your bank of knowledge with more information won't be a bad idea.

This side effects associated with coronavirus though has been regarded as not something to really panic about after the principle of consequatialism was invoked. (Risk assessment conducted showed that, the benefits of the vaccine outweighed the risk).

Going furthermore and deep into the discussion without bringing you up to speed on the meaning of the word - 'Thrombotic Thrombocytopaenia' might make the discussion uninteresting.

Worry less, I will simplify every term when necessary. I am on a mission to make hive, the compendium of knowledge and a place where you can get information with less ambiguity. A message passed in any form or way, provided the end user understood, then the message is assumed clear.

Thrombosis formation and terminologies explained!

Let's begin by understanding what thrombocytes, thrombosis and thrombocytopenia is, this will give us a good head start.

Thrombocytes by definition are the components of red blood cells. A special type of cells that play huge role in prevention and control of bleeding through the formation of blood clot (what stops bleeding) or a thrombus (a blood clot within the blood vessels and remains there).

In essence, blood clot essentially formed arrest bleeding and it is named depending on where is formed and the nature. It could be a thrombus, formed inside the blood vessels (e.g. veins and arteries).

In situations where these thrombus dislodge and travel from the region of formation to another point, it is referred to as an embolism (a very dangerous situation). I want to make sure you fully understand everything we will discuss later on. Keep reading!

They are also known as platelets and are the smallest cell of the blood averaging about 2 - 4μm in diameter. Being the smallest cells, they are the most numerous ranging from 150,000 to 400,000 per cubic millimeter. So in all, platelets are the basis for blood clot.

Thrombosis formation

In situations where these block veins or arteries in the body, it is reference to as Thrombosis. Blocked veins and arteries definitely would lead to ischemia (restrictions of blood flow to vital tissues and organs) and Necrosis.

Necrosis (a form of cell injury which results in the premature death of cells in living tissue) will definitely occurs since the affected organs or parts of the body's nutrients and oxygen supply has been cut short as a result of the blockage.

Some of the symptoms usually associated with thrombosis includes pain and swelling in the affected area, chest pain and numbness on one side of the body.

In situations where the level of platelets are less than normal range or severely low in level, this condition is referred to as Thrombocytopenia. In essence, thrombocytopenia is a medical condition that is characterized by platelets lower than 150,000/microliter and it is usually associated with a risk of severe
bleeding and thrombosis. Hope it is making more sense to you now?

So if Thrombosis is blood clot formation inside blood vessels and blockage of this vessels by the blood clot. What then is Vaccine-induced Thrombotic thrombocytopenia, (VITT). Would you want to try? I will allow you think through that while I quickly discuss the most important factors and conditions that usually leads to thrombosis.

The Virchow's Triad

You cannot talk about thrombosis without mentioning the virchow's triad which is an embodiment of the three most important factors that cause or lead to thrombosis. In no particular order, we have

•Hypercoagulability
•Venous stasis and
•Endothelial injury/dysfunction

The three factors above can individually initiate and contribute to the formation of thrombosis.

The Virchow's Triad

Hypercoagulability is simply the increased tendency of the blood cells to form coagulation or clump together easily instead of moving and flowing freely within the blood vessels.

Cells with high tendency of always clumping together can cause the formation of thrombus. When it comes to Venous Stasis, it refers to the haemodynamic changes to the movement of the blood cells within the vessels.

Naturally, blood cells flow in a laminar manner without any form of obstruction, but in situation where there is turbulent or haphazard flow, the tendency of the blood to clump is extremely high thus, leading to thrombus formation. It becomes worst if the blood cells are not constantly flowing.

The third factor which is endothelial injury or dysfunction refers to injury to the smooth endothelial wall of the blood vessels. Should anything happen to the endothelial wall, the consequence is a activation of the clotting system which comes in to repair the damage.

Comparing the Normal and abnormal endothelial with thrombus

By nature, the endothelial wall is smooth and this is ensure by vasoactive factors like Nitric oxide (NO), Prostacyclin (PGI2), TXA2 etc. All this factors work to maintain the antithrombogenic (inability to form clot) nature of the blood vessels. Imagine that the wall or route through which blood moves is sticky or adhesive in nature, it simply means that the cells will stick to the walls and should this continue, there will definitely be clumping and serious aggregation of cells thus leading to blood flow obstruction.

We have been able to understand how the three factors listed above can affect and trigger thrombosis. We have been able to also explain the major terminologies relating to the topic. So it is safe at this point to say that Vaccine-induced Thrombotic Thrombocytopaenia, (VITT) is simply thrombosis caused by or arising as a consequence coronavirus vaccine administration and leading to drastic fall in platelets level or concentration in the blood.

The fall in platelet level could be as a result of its use in the formation of the internal clots (Thrombus) or probably due to the destruction of this platelets by auto antibodies formation post vaccination. When platelets are used up more than the rate at which they are produced level, the consequence is definitely a fall in its value.

The question now is; Why and how does the coronavirus vaccine cause thrombosis in patients? What could be the possible reason and why is it that it is mostly associated with the AstraZeneca COVID-19 and Johnson & Johnson vaccine? as reported in the review by Brit Long and colleagues, 2021. Although the cases are rare as earlier stated, still, it calls for an attention.

So far, there has not been much researched on this topic and the possible reason why it happens. But the few available facts are what I will be sharing in due course regarding the pathophysiology (i.e the the functional changes that accompany a particular disease) of the coronavirus Vaccine-induced Thrombotic thrombocytopenia (VITT).

It's of no doubt that coordinated global efforts by several health agencies, research groups and organizations led to the development of COVID-19 vaccines, followed by its emergency use authorization within nine months of the pandemic, evident in the publication made by FDA in 2020.

Today, these coronavirus vaccines are now widely available for public administration. The vaccines so far have been considered safe and effective in preventing severe infection, hospitalization, and death, WHO, 2021.

No doubt, the vaccines are safe and efficacious, based on WHO report 2021 but still, the reported adverse reactions has to be addressed to possibly convince those that are still doubting the safety profile of the vaccine and one of the major reasons for hesitancy by individuals towards the available vaccines, Ismail Elalamy et al, 2021

Pathophysiology of Vaccine induced Thrombotic thrombocytopenia

Till date, the exact pathophysiology of VITT is still yet to be fully understood but based on the review done by Syed Hassan Ahmed and colleagues, 2021:

VITT is reported to be in close resemblance with heparin-induced thrombocytopenia (HIT), a medical condition characterized by
thrombocytopenia, and the presence of antibodies against the Heparin-PF4 complex.

A better explanation to the above is that, there is a formation of antibodies that act against platelet antigens. Because of this, it in turn triggers massive activation of platelet, its subsequent aggregation, and ultimate consumption, which reduces platelet count and results in thrombosis. This mechanism is similar to heparin (An anticoagulant - substance that has the ability to prevent the blood from clotting) induced thrombocytopenia, (HIT).Brit Lon et al., 2021.

By implication, the explanation above is not far from what we earlier pointed out regarding the development of auto antibodies against the platelets thus, leading to their destruction and consequent fall in level (thrombocytopenia). Though, there is still a gap to be filled in this regards; how then are the antibodies formed if at all of a fact, the possible pathophysiology proposition is confirmed.

Another point to also ponder on is the fact that, the said VITT is mostly associated with only AstraZeneca and Johnson & Johnson COVID-19 Vaccines. So why is it not associated with the other types like BioNTech, Pfizer vaccine, Moderna etc. Since both AstraZeneca and Johnson & Johnson are both made up of recombinant adenovirus vectors from a chimpanzee adenovirus or even human virus respectively that encodes for the severe acute respiratory syndrome coronavirus 2 aka (SARS-CoV-2) spike protein.

Vaccine design overview

Could it be that the components of the vaccines have a role to play in this regard. Another area worth diving deeply into through research. I believe in due time and in years to come, we will definitely have an answer, but in the mean time, we keep researching.

Just for the record, according to the research, it has been observed that VITT occurs mostly occurs in patients aged < 55 years and is associated with high morbidity and mortality, Chih-Cheng Lai et al., 2021. If this happens to be the case, why then is it not with older people since these group are mostly at higher chances of developing thromboembolism, Peter L. Gross and Chan C Chan, 2021. These are another area worth researching deeply on.

Areas of the body mostly implicated with VITT and incidence rate so far

Research has shown that VITT occurs mostly in atypical areas like the brain - Cerebral venous thrombosis ,CVT (a cerebrovascular disease with diverse clinical manifestations that often affects young adults) and also in the hepatic, portal or the splanchnic veins - (Mesenteric vein thrombosis), Brit Lon et al., 2021.

The above regions are usually not regular spots or common areas thrombosis are well known to occur.

Though the incidence of VITT is extremely low. So far, the Published estimates of the incidence of VITT ranges from 1 case per 26,000 to 1 case per 127,000 doses of AstraZeneca/COVISHIELD administered to people, COVID-19 science table.

These estimates differ from one country to another, with countries like Norway and Denmark being the countries with highest rate of incidents. As of April 28, 2021, the rate of VITT in Canada has been estimated to be approximately 1 per 100,000 doses.

The World Health Organization(WHO) on 7 April 2021. As per the European Medicines Agency (EMA), revealed that the incidence of VITT after vaccination with Oxford-AstraZeneca (ChAdOx1 nCoV-19) is estimated to be between 1 in 125,000 and 1 in 1 million and very importantly, more than 80% of the patients in the reported cases of VITT were females and aged between 20 to 55 years of age.

Indeed, the incidence rate is massively low and rare, regardless, it is much better to douse the fear in people by trying as much as possible to find out through research the real reason behind the VITT and the possible way out. Or better still, we resort to using those that have no serious adverse effects.

The latter obviously won't be so easy to achieve considering the fact that one of the said vaccines is from UK, I won't be surprised seeing politics playing out in that regards. Who would want to be kicked out of business? Definitely no one.

I won't blame some of my colleagues that keep reiterating that COVID-19 is just another opportunity for pharmaceutical industries, biotech companies and most biomedical firms to make money. They would want to recover their billions or millions of dollars which they have invested in finding a possible cure to the COVID-19.

Now they have most likely found the solution through vaccine production, the time for profit is next, they probably begin to engineer the pathogen, replicating its look alike and call it all manner of names, meanwhile, they still have the solution, telling the masses to come for more shots.

As much I hate rumours or unfounded statements, I am tempted to agree with him them, though not in totality. The aspect of recommending more shots as a solution to the Omicron variant actually made me to wonder, could it real be true that these 'guys' are really doing this to humanity.

Well, I wouldn't still want to believe this since it is just a mere assumption with no verifiable proof. As far as I am concerned, it remains an assumption unless proved with facts.

Any possible treatment so far for VITT?

It has been reported that VITT associated with coronavirus is not the regular type of thrombosis, research has shown that VITT is more serious and fatal than the regular thrombosis. Reason being that VITT is supposedly caused by antibodies that recognize platelet factor 4 that is bound to platelets leading to platelet activation and possible activation of other cells like the neutrophils.

Parallels in Pathogenesis of VITT and autoimmune HIT

These cascade of reaction results to significant or marked initiation of the coagulation cascade system and clinically significant thromboembolic complications Theodore E Warkentin, 2021.

The key difference or distinctive feature of VIIT from HIT is that, antibodies associated with HIT are unable to activate the platelets to cause aggregation resulting to thrombosis while those of VITT can. This feature is taken advantage of in treatment and management of patients suffering from coronavirus VITT.

Decision Tree for Diagnosing and Ruling Out VITT

Patients with possible VITT if subjected to testing, are usually seen having thrombocytopenia, markedly elevated d-dimers (Markers of coagulation disorders), and low fibrinogen (Proteins that are involved in clotting process) Vanessa E. Kennedy and colleagues, 2021. So t

Treatment usually involves administration of intravenous Immuno globulin G to mop up the antibodies against the platelets and also administration of non heparin anticoagulant.

Research has shown that early treatment offers good prognosis as seen in the cases reported by Vanessa E. Kennedy and colleagues, 2021.

Do not be scared for nothing though, the adverse effects of the vaccines are indeed rare and reports have shown it. But if you feel you are not comfortable with the one reported to have adverse effects, you can probably make your decision on which to go for.

Though I don't know if individuals have that power. Regardless, COVID-19 vaccines so far are safe and very effective to my best of understanding. We only hope we don't see more cases that will defy these vaccines.

I will always be around to update us if need be. For further readings, kindly explore the reference section of this article.

Till I come your way again, have a blessed day.

Thanks for reading.

References
_{•Possible Side Effects After Getting a COVID-19 Vaccine
•Platelets biochemistry
•Physiology of the endothelium
•The Endothelium and Its Role in Regulating Vascular Tone
•FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine
•Vaccine-Induced Thrombotic Thrombocytopenia Following Coronavirus Vaccine: A Narrative Review
•Coronavirus Vaccine and safety
•The Oxford/AstraZeneca COVID-19 vaccine: what you need to know
•SARS-CoV-2 Vaccine and Thrombosis: An Expert Consensus on Vaccine-Induced Immune Thrombotic Thrombocytopenia
•Pfizer-BioNTech Vaccine
•Thrombosis with thrombocytopenia syndrome associated with COVID-19 vaccines
•COVID-19 vaccines and thrombosis with thrombocytopenia syndrome
•Thromboembolism in Older Adults
•SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
•Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)
•VITT following Ad26.COV2.S vaccination presenting without radiographically demonstrable thrombosis}