Blood clots and TAM receptors signalling after receiving COVID-19 vaccines

 

Blood clots and TAM receptors signaling after receiving COVID-19 vaccines

The blood clots happening to vaccinated people around the world are probably due to the effects of the mRNA vaccine messing up with the TAM (Tyro3, Axl, Mer) receptors and their ligands Gas6 (Growth arrest-specific protein 6) and Protein S which they play an important role in many cellular processes such as resolution of inflammation and phagocytosis. Notably, they were found to have an important function in vasculature, acting as a pro-survival factors and regulators of angiogenesis and ANTI-COAGULANTS.

TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the proteins Gas6 and Protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a pro-inflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, I compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S+/−, Gas6−/−, TAM−/−, and variations of these). In this manner, I aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation and blood coagulation.

Protein S is produced by a variety of cell types (eg, hepatocytes, endothelial cells, megakaryocytes, osteoblasts). It contains an amino terminal γ carboxyglutamic acid (GLA) domain, followed by a thrombin-sensitive loop region and 4 epidermal growth factor–like domains ending with the carboxy-terminal (C-terminal), consisting of 2 laminin G repeats that together comprise the sex hormone–binding globulin domain (Figure 1B). The C-terminal region is sufficient for TAM receptor binding and phosphorylation.

Protein S circulates in plasma at a concentration of 346 nmol/L and serves as an anticoagulant by working as a nonenzymatic cofactor for activated protein C in the breakdown of coagulation factors (F) Va and FVIIIa. It is further capable of binding FXa and FVa directly in that it can autonomously inhibit coagulation. Factor Xa is also inhibited by protein S through acting as a cofactor for tissue factor pathway inhibitor. In humans, it exists in a free active form (30% to 40%) and in an (almost) inactive form bound to C4b-binding protein (60% to 70%).It is therefore plausible that in human protein S is apt to affect the complement system.

Heterozygous deficiency of PROS1 is associated with an elevated risk for developing thrombosis, whereas homozygous deficiency is incompatible with life or leads to neonatal purpura fulminans in rare cases.

With respect to hemostasis, all 3 TAM receptors are located on platelets and mediate thrombogenesis and platelet stabilization. Platelet stabilization occurs after integrin activation, granule secretion, and platelet aggregation through platelet-to-platelet contact. Gas6 levels in plasma were higher in patients with venous thromboembolic accident as compared with healthy individuals.

Measurement of free PROS1 levels in the circulation is not currently part of the standard blood work-up for patients, but I would suggest that such measurements may be informative and warranted in patients that were inoculated with a COVID-19 vaccine to check if there's evidence of coagulopathy and high D-dimer levels.