Well, this is going to be a fawkin long one. I've tried editing it down but holy fuk there's just too much basic detail I don't want to leave out. And even then I'm only scraping the surface of this topic. Also I've amassed a crap tonne of studeez on my phone related to this, not gonna poast due to room so if anyone is interested in seeing anything specific just DM me. Lastly, as far as the specific Vax is concerned, I've focused all my attention on the Pfizer Cominarty version. As such I'm unsure if all SARS-CoV-2 Vaxs use the same Spike protein.
BLOOD CLOTTING: The Coagulation Cascade
There is a dual pathway that is responsible for coagulation and the formation of clots. Platelets, and fibrin, are the big players in these pathways. Thrombin interacts with fibrinogen, creating fibrin strands. These strands crosslink and gather to form a fibrin clot. Fibrinogen also promotes clotting by activating platelets (which are otherwise dormant in blood) and forming platelet bridges. We will see later how this all ties together as a single clot.
Fibrin also limits clot formation, and degrades/dissolves formed clots. Note: a clot is intended to have a transient/temporary function (inhibit bleeding/vessel wall damage); once the damaged area has been healed, the clot dissolves.
How clots are dissolved:
Fibrin can activate plasmin, an enzyme in the blood that degrades many blood plasma proteins...including fibrin/platelet clots. This degradation is called fibrinolysis.
Enter D-dimers:
Plasmins degradation of the fibrin clot releases D-dimers (Dd). Detection of Dd in blood is used as a clinical test for fibrinolysis (the breakdown of clots). Dd half life is short, 8 hours. Dd is cleared by the kidneys.
So what is the COVID vax possibly doing, such that we might see an increase in D-dimer?
I'm seeing at this stage 3 potentials:
1) Vax is triggering the Coagulation cascade, resulting in an increase in fibrinolysis
2) Vax is increasing Fibrinolysis
3) Vax is causing whatever initiates the Coagulation cascade
(1) seems unlikely to me.
(2) possible, the affected Dd patients might already have abnormally high clotting that is now being hyper-degraded
(3) we need to look more closely at what causes or initiates the Coagulation cascade, or clotting, in the first place
What initiates clotting?
Specifically: injury to the endothelial lining of blood vessels. When this occurs, blood exposed to the damaged area initiates the dual pathway: a change in or triggering of platelet activity, and fibrin formation.
A clot itself consists of 2 actions previously mentioned. Primarily, triggered platelets form a plug. Secondarily, and simultaneously, fibrin strands form to strengthen the platelet plug.
Once the clot has achieved its purpose (repair damage to endothelial lining), fibrinolysis occurs.
Again, fibrinolysis prevents clots growing beyond what is needed for repair and becoming problematic (significant vessel narrowing, or clot breaking away before being degraded and blocking vessels elsewhere ie embolism).
Plasmin breaks down the fibrin mesh and the platelet plug. A byproduct of this process is Ddimer (Dd). Dd is thus a marker for fibrinolysis.
We also typically find Dd levels elevated in most people with acute thrombosis, see an increase with age, post-surgery, pregnancy, cancer, chronic inflammatory conditions...and infection.
If endothelial damage triggers the Coagulation cascade, what might cause endothelial damage?
OK here's where things get real interdasting and important for our demographic.
*diabetes
*smoking
*sh1tty lipid levels
*high blood pressure
*hypoxia
*bacterial or viral infection
Now, my initial enquiry here was in regards to the Vax and how it might be implicated in somehow increasing Ddimer. This will be my focus, but I will reintroduce how AAS is also involved if and when appropriate.
With the Vax, I think we are really interested in acute damage to the endothelium in a short time frame. As such we can rule out diabetes, smoking, high blood pressure and lipids from our list at least for the time being as these are all chronic in nature.
This leaves us with hypoxia and infection. The connection with SARS-CoV-2 should be obvious. Hypoxia is crudely where insufficient oxygen is supplied to tissues to sustain normal function.
We have studies demonstrating SARS-CoV-2 (I'll just refer to it as Covid) causes endothelial damage. Vascular endothelium can be infected by Covid, and Covid induces endothelium inflammation, or endotheliitis.
The Pfizer Vax contains genetic code for part of the Covid virus, called the "Spike protein". This SProtein is itself claimed to impair endothelial function, and alone can damage endothelial cells. How? By downregulating ACE2.
Quick recap:
Endothelial damage--->Coagulation cascade--->clot formed--->fibrinolysis--->Ddmer byproduct
The renin–angiotensin system (RAS):
Ugh I know, more terminology. But trust me, if you get through this you'll see how everything ties together.
If you're familiar with ACE inhibitor or ARB drugs, you might also be familiar with the RAS.
The main function of the RAS is to regulate blood pressure and vascular resistance. It does this via various pathways (electrolyte balance, fluids, oxygenation).
With the RAS, we are mainly interested in Angiotensin1 (Age1), Angiotensin2 (Age2), and Angiotensin-converting enzyme 2 (ACE2).
Age1 is a vasodilator, so it helps widen and relax vessels.
Age2 is a vasoconstrictor, so it helps narrow vessels.
ACE2 is a kind of brake on Age2, converting it to Age1. It is therefore responsible for not only regulating blood pressure, but helping with wound healing (including endothelial damage) and inflammation. Remember hypoxia? ACE2 is also involved in oxygenation of body tissue. Age2 can increase inflammation and the death of cells in the alveoli which are critical for bringing oxygen into the body; these harmful effects of Age2 are reduced by ACE2.
So ACE2 is a good guy. But not everyone has the same number of ACE2 through their body. This is one variable contributing to variances in Covid symptoms across individuals.
ACE2, yay!!
However...the Covid virus, via the Spike protein, binds to ACE2, inhibiting its normal function. ACE2 is thus considered the entry point for Covid. This effectively removes the brakes from downstream chemicals, leaving Age2 to injure tissues especially the heart and lungs.
We have a paradox
ACE2 sucks, it lets Covid into our bodies. Less ACE2!! Less COVID!!
ACE2 is awesome, it improves vascular and endothelium function. It lowers inflammation. More ACE2!!
We need more ACE2, to combat the negative impact Covid has on heart, lungs, and vessels. But this increases the viral load of Covid. Ugh!!
There is one potentially promising angle to improve outcomes, and that is to decrease Age2 via ARBs like Telmisartan. There are preliminary studies looking into just this. I've also come across non pharma ways of doing this, but as to their potency who knows. Estrogen, incidentally, is good for Age1 and ACE2 function.
The AAS angle
It should be clear we don't want to minimize ACE2 function, Covid already does that. We want to promote its healthy levels, and so too Age1. Our overall goal should be to maximize endothelial and vascular health, or minimize anything deleterious. We need a properly functioning RAS to do this.
AAS is known to have negative impacts on vascular health and function. Aside from the impact on lipids, it also affects platelet function and Coagulation factors in general, and damages the endothelium. There are studies showing this occurs even at TRT doses.
The RAS tie-in for our demographic is clear. RAS health is impacted by Covid and potentially the Vax, and it is impacted by AAS use. I'm even more convinced now that focusing on Cardiovascular health is absolutely paramount.
