7. Haemostasis
1
We will briefly touch upon the structure of blood vessels.
Haemostasis is coagulation.
1 – of course, we want our blood to clot if we get an injury but why is it important that
coagulation is only initiated when we get damage to a vessel wall, why is not a good thing if
we were to bleed excessively and not control blood loss and why is it not a good thing if we
have this increased tendency to clot spontaneously.
2 – what are the different factors involved within coagulating or clotting blood, that ranges
from platelets to coagulation factors.
3 and 4 – what is involved in those pathways and what do they do.
5 – describe the different types of tests we can perform in the lab to be able to assess
coagulation.
1 – it is the damage of those blood vessels and through that damage blood is lost.
3 – there are a number of these, the royal family have a deficiency within a given
coagulation factor.
4 – its all well and good that we can activate coagulation when we need to, but we don’t
want it to happen all of the time as the formation of spontaneous clots can give rise to
strokes and heart attacks.
5 – once we have formed that clot and stopped the blood loss, how can we then break down
that fibrin clot.
Fine balance – we don’t want to bleed excessively anymore than we want clots to form.
Primary – the injury to the blood vessels will cause lots of blood to flow out of that injured
site and you will get the interactions between the damaged vessel wall and the platelets
which are flowing past that damaged vessel wall which will recognise the damage and begin
to stop that blood flow by forming a primary platelet plug. This primary platelet plug isn’t
the end of coagulation – it is one of the first stages and a temporary measure and it needs
strengthening.
Secondary – involves intrinsic and extrinsic coagulation pathways – they will then merge to
form the common pathway and that will give rise to fibrin strands and its those fibrin strands
which act like glue that aim to support and strengthen the primary platelet plug thereby
stopping the blood loss.
All the phases in the primary and secondary haemostasis interact and integrate and many of
them occur simultaneously.
The inner most layer in white is the lumen – where the blood cells will be flowing through
but if we talk about the vessel wall itself the innermost layer is the tunica intima which is
lined with the endothelial cells.
The next layer as we move out is the tunica media and the most outer layer is the tunica
adventitia.
Intact epithelial cells line the intima – these are referred to as being anti-thrombotic because
they produce molecules such as heparin and heparin is a cofactor for antithrombin and that
aims to prevent coagulation.
, 7. Haemostasis
When we get damage to the endothelium, we get the exposure of ECM protein which are
normally sequesters by those intact endothelial cells. The ECM proteins include collage,
elastin and fibronectin and that will initiate coagulation.
During injury we get vasoconstriction, and this is due to the contraction of smooth muscle
cells, and this is mediated by a number of factors such thromboxane, endothelin 1,
adrenaline and ultimately, we get constriction of the smooth muscle cells that narrow the
lumen of the blood vessel, reducing the amount of blood that can be lost because it slows
blood flow.
The cysteine-rich glycoproteins vWf is able to bind to a number of components upon the
surface of platelets such as glycoprotein 1b, 2b and 3a and when we get damage to the
endothelial cells within the blood vessels we get exposure of ECM proteins – vWf is able to
bind to a number of those ECM proteins and therefore able to kickstart coagulation.
Example of this include being able to bind to elastin and to collagen.
It mediates the adhesion of platelets to the damaged blood vessel and vWf acts as the
bridge between the platelets and the damaged blood vessel.
It is secreted constitutively (all of the time) and when it’s not being secreted it is stored in
endothelial cells as Weibel-Palade bodies and these are the rod shaped structured shown on
the right – on the electron microscopy image.
Digestion of these large multimers is mediated by the plasma metalloprotease ADAMTS-13.
It is synthesised in megakaryocytes which will then form the platelets and it is stored within
those platelets within alpha granules and each platelet contains roughly about 18 alpha
granules each.
Platelets are derived from megakaryocytes – these megakaryocytes will begin to bud off
their cytoplasm to form pro-platelets and each megakaryocyte can give rise to 2000-3000
platelets each.
The production of platelets is referred to as thrombopoiesis and in a typical healthy
individual you get 10^11 platelets produced each day.
Because of their small size they will flow towards the edges of the circulation and have most
contact with the blood vessel wall that’s helpful due to their involvement in coagulation.
Platelets don’t exist in an activated state, and they require activation.
Alpha granules contain clotting factors such as 5 and 8.
Dense bodies are less common – you have around 8 per platelet and these contain the
vasoconstrictor serotonin, but they also contain calcium, ATP and ADP.
Lysosomes contain acid hydrolase enzymes that are involved within the degradation of
blood clots.
Vasoconstriction will occur to reduce the amount of blood flow to ultimately reduce the
amount of blood loss.
Here we have the blood vessel and the endothelial cells which line the intima of the blood
vessel (the inner most layer next to the lumen) – damage to those endothelial cells so they
are lost and this leads to the exposure of ECM proteins such as collagen – vasoconstriction at
the site to reduce the amount of blood loss and this could be due to things such as
adrenaline acting on the smooth muscle cells, endothelin which is produced at the site of the
damage – these will them promote that vasoconstriction.
1
We will briefly touch upon the structure of blood vessels.
Haemostasis is coagulation.
1 – of course, we want our blood to clot if we get an injury but why is it important that
coagulation is only initiated when we get damage to a vessel wall, why is not a good thing if
we were to bleed excessively and not control blood loss and why is it not a good thing if we
have this increased tendency to clot spontaneously.
2 – what are the different factors involved within coagulating or clotting blood, that ranges
from platelets to coagulation factors.
3 and 4 – what is involved in those pathways and what do they do.
5 – describe the different types of tests we can perform in the lab to be able to assess
coagulation.
1 – it is the damage of those blood vessels and through that damage blood is lost.
3 – there are a number of these, the royal family have a deficiency within a given
coagulation factor.
4 – its all well and good that we can activate coagulation when we need to, but we don’t
want it to happen all of the time as the formation of spontaneous clots can give rise to
strokes and heart attacks.
5 – once we have formed that clot and stopped the blood loss, how can we then break down
that fibrin clot.
Fine balance – we don’t want to bleed excessively anymore than we want clots to form.
Primary – the injury to the blood vessels will cause lots of blood to flow out of that injured
site and you will get the interactions between the damaged vessel wall and the platelets
which are flowing past that damaged vessel wall which will recognise the damage and begin
to stop that blood flow by forming a primary platelet plug. This primary platelet plug isn’t
the end of coagulation – it is one of the first stages and a temporary measure and it needs
strengthening.
Secondary – involves intrinsic and extrinsic coagulation pathways – they will then merge to
form the common pathway and that will give rise to fibrin strands and its those fibrin strands
which act like glue that aim to support and strengthen the primary platelet plug thereby
stopping the blood loss.
All the phases in the primary and secondary haemostasis interact and integrate and many of
them occur simultaneously.
The inner most layer in white is the lumen – where the blood cells will be flowing through
but if we talk about the vessel wall itself the innermost layer is the tunica intima which is
lined with the endothelial cells.
The next layer as we move out is the tunica media and the most outer layer is the tunica
adventitia.
Intact epithelial cells line the intima – these are referred to as being anti-thrombotic because
they produce molecules such as heparin and heparin is a cofactor for antithrombin and that
aims to prevent coagulation.
, 7. Haemostasis
When we get damage to the endothelium, we get the exposure of ECM protein which are
normally sequesters by those intact endothelial cells. The ECM proteins include collage,
elastin and fibronectin and that will initiate coagulation.
During injury we get vasoconstriction, and this is due to the contraction of smooth muscle
cells, and this is mediated by a number of factors such thromboxane, endothelin 1,
adrenaline and ultimately, we get constriction of the smooth muscle cells that narrow the
lumen of the blood vessel, reducing the amount of blood that can be lost because it slows
blood flow.
The cysteine-rich glycoproteins vWf is able to bind to a number of components upon the
surface of platelets such as glycoprotein 1b, 2b and 3a and when we get damage to the
endothelial cells within the blood vessels we get exposure of ECM proteins – vWf is able to
bind to a number of those ECM proteins and therefore able to kickstart coagulation.
Example of this include being able to bind to elastin and to collagen.
It mediates the adhesion of platelets to the damaged blood vessel and vWf acts as the
bridge between the platelets and the damaged blood vessel.
It is secreted constitutively (all of the time) and when it’s not being secreted it is stored in
endothelial cells as Weibel-Palade bodies and these are the rod shaped structured shown on
the right – on the electron microscopy image.
Digestion of these large multimers is mediated by the plasma metalloprotease ADAMTS-13.
It is synthesised in megakaryocytes which will then form the platelets and it is stored within
those platelets within alpha granules and each platelet contains roughly about 18 alpha
granules each.
Platelets are derived from megakaryocytes – these megakaryocytes will begin to bud off
their cytoplasm to form pro-platelets and each megakaryocyte can give rise to 2000-3000
platelets each.
The production of platelets is referred to as thrombopoiesis and in a typical healthy
individual you get 10^11 platelets produced each day.
Because of their small size they will flow towards the edges of the circulation and have most
contact with the blood vessel wall that’s helpful due to their involvement in coagulation.
Platelets don’t exist in an activated state, and they require activation.
Alpha granules contain clotting factors such as 5 and 8.
Dense bodies are less common – you have around 8 per platelet and these contain the
vasoconstrictor serotonin, but they also contain calcium, ATP and ADP.
Lysosomes contain acid hydrolase enzymes that are involved within the degradation of
blood clots.
Vasoconstriction will occur to reduce the amount of blood flow to ultimately reduce the
amount of blood loss.
Here we have the blood vessel and the endothelial cells which line the intima of the blood
vessel (the inner most layer next to the lumen) – damage to those endothelial cells so they
are lost and this leads to the exposure of ECM proteins such as collagen – vasoconstriction at
the site to reduce the amount of blood loss and this could be due to things such as
adrenaline acting on the smooth muscle cells, endothelin which is produced at the site of the
damage – these will them promote that vasoconstriction.
