Homeostasis Thrombogenesis

Dr. Alex Gatt

Going back in evolutionary time, all vertebrates have developed a protease known as thrombin
which is a key player in coagulation. This is used to block aneurysms, when people undergo
femoral artery catheterization a weakness is formed in the artery a false aneurysm thrombin is
in!ected into it and immediately a clot is formed.
"ertain creatures have retained certain essential features, non#essential elements have become
vestigial thrombin has been a constant element in evolution. $eeches, in fact, secrete a direct
thrombin inhibitor in order to facilitate sucking of blood. "oagulation is extremely important
certain coagulation factors are needed for compatibility with life.
A clot re%uires a platelet and fibrin meshwork. &t does not stick to the endothelium, but it grows
from the site of the damage into the lumen. The endothelial lining is an extremely powerful
epithelium and possesses an anti#coagulant layer to prevent clogging of vessels. The blood clot
grows and embolises, until the clot buds off, eventually retracting to a smaller size.
Primary Homeostasis
This relates to the platelets, the smallest of cells in the body, and like the '(" they are anucleate
but are active due to the presence of mitochondria. They are produced as buds in the bone marrow
from very large cells) the megakaryocytes *hyper#lobated nucleus, platelet#like cytoplasm+. The
lifespan is around ,-#,. days, in normal circumstances, however in other cases they can be
destroyed in minutes/hours.
The platelets has various functions. &t resembles very much a cookie the chocolate chips are
analogous to the granules in the platelet. The membrane of the platelet is lipid in nature and has 0
important functions1
it has a huge amount of receptors which allow the body to acknowledge that something is
wrong with the endothelial layer
in the bloodstream, platelet always flow at the periphery of the lumen, as they are
sentinel cells
underneath the endothelial layer the (2 and smooth muscles may come in contact with
the blood
the platelet has receptors for collagen fibres, 3on 4illerbrand factor, etc. # it attaches to
them and to the site of in!ury
a cascade of activating reactions attract more and more platelets upon attachment to
site of in!ury, an internal effect in the platelet is triggered, one that targets the granules
alpha *clotting factors+ and dense *agonists # chemicals which activate platelets factor+
granules
thromboxane pathway blocked by aspirin
the AD5 receptor activates other platelets and enhances its own activity the 506,0 is
the receptor blocked by clodiplogrel) an anti#platelet agent
when resting, the platelet membrane has an internal layer of phospholipids which are more
active when activated not only the granules are released but also the bilayer is flipped,
exposing active phospholipids to the outside
&f you lack one of the receptors involved in the cascade, you have a higher tendency to bleed.
The actual mechanism of coagulation in arteries and veins is exactly the same the only difference
lies in the structure of such vessels and the different pathologies in such vessels. &n arteries,
atherosclerosis is common but if the endothelium is damaged primary and secondary homeostasis
are present. $ines of 7ahn are lines of treatment used by the cardiologists after an infarct. The
pathophysiology in veins is different in the leg veins clot formation is due to stasis thus they look
8currant !elly#like8.
Thrombocytopenia low platelet count *9,.-#.--+
Secondary Homeostasis
5hospholipids act as a platform to sustain clotting. The scramblase mechanism is missing in patients
such as those suffering from :cott8s syndrome. ;aemophilia A patients suffer from congenital
bleeding, its gene lies on the < chromosomes and mainly affects boys. :uch patients bleed
spontaneously, even though the primary homeostasis is normal, as they lack =actor 3&&& *!ust a
single clotting factor+ which is extremely important.
5latelets only form a flimsy clot they re%uire a fibrin mesh which traps platelets and other cells in
the clot. A strong fibrin meshwork denotes a strong clot. ;ow does fibrin form>
FI - fibrinogen
FII - prothrombin
Tissue factor is a transmembrane receptor for =actor 3&& and =3&&a