Thrombosis Flashcards
What is coagulation
Coagulation is an inflammatory response to injury that is initiated by a coagulation cascade that
prevents blood loss.
How is blood loss prevented in coagulation
This is through sealing of the wound that is aided by vasodilation that delivers
inflammatory products to the wound
What causes ischaemia of the brain
Ischaemia of the brain caused by embolic stroke either from
the carotids or the heart is an example of where coagulation can go wrong. The result is a region of
neuronal cell death due to lack of blood flow. This can be fatal or very debilitating.
What can the body’s response to damage be split into
The body’s response to damage is divided into two parts; primary and secondary haemostasis.
What is primary heamostasis
Primary haemostasis is the activation of platelets that cause them to come together and stick along
with RBCs to become a clot (aggregation).
What is activated in secondary heamostasis
Fibrinogen is then activated in secondary haemostasis to
form a firmer more rigid fibrin clot that is cross linked and this replaces the initial blood clot.
When fibrinogen is formed what does it convert to
Fibrinogen is converted to fibrin by the protease thrombin that is itself activated by a series of
upstream reactions. There is in fact a whole cascade of reactions that culminate in the activation of
fibrinogen to fibrin.
What two processes occur due to low levels of thrombosis
Anticoagulants can prevent thrombosis whilst fibrinolysis breaks down the clots
and reverses them. These two processes in fact occur all the time in the body in response to low
levels of thrombosis.
Where can thrombosis form
Thrombosis can be formed in arteries or veins with the event occurring in each type of vessel being
very different.
How does arterial thrombosis form
Arterial thrombosis mostly results from atheroma rupture or damage to the
endothelium. They tend to be platelet-rich mostly primary clots that can block downstream arteries.
This clot can in fact be dislodged and travel down to essential blood vessels in the lungs or in the
brain where the consequences are severe.
How does venous thrombosis form
Venous thrombosis is the more serious type of thrombosis
due to them happening more often. They often result from stasis or hyper-coagulant state and the
clots formed are platelet-poor ‘red’ thrombus. They are mostly secondary clots and may move into
pulmonary circulation and block the lungs or even the heart itself.
What must the body balance between - 2 processes
The body is constantly under the balance of coagulation and fibrinolysis.
What factors does flowing blood interact with to initiate clotting
In a blood vessel, flowing
blood is surrounded by endothelial cells with a subendothelial layer of cells underneath this that are
not normally in contact with blood. When this layer is exposed, the blood interacts with tissue factor
(TF) that initiates clotting (comes into contact with factors in the blood). Blood can also interact with
von Willebrand factor that is also found in circulating blood, with the result of the interaction being
that platelets in the blood bind to this substance to start a clot.
Why is a clot able to start without too much tissue damage
A clot can be started without too
much tissue damage due to the circulating von Willebrand factor (slowing down blood).
What are the mechanisms that prevent blood from clotting
There are a
number of mechanisms by which blood clotting is prevented. Antithrombin and heparan binding
together inhibits clotting whilst prostaglandin I2 and nitric oxide (produced by the endothelium to
cause vasodilation) both inhibit platelets. There are all mechanisms to breakdown clots when they do
form.
How are clots broken down
Tissue plasminogen activator activates plasminogen to become plasmin that then goes on to
act on clots and break them down into D-dimers (breakdown products).
What three mechanisms are in balance
The mechanisms for clotting,
resisting clotting and reversing clots are all in balance.
What does static blood lack and tend to do
Static blood lacks kinetic energy and tends to clot (lack of activity like patients in bed and
passengers in long haul flights).
What can endothelial damage cause
Endothelial damage caused by surgery or a cannula can also cause
clotting as the subendothelial layer is exposed.
What factors increase ones hyper- coagulation state
Factors that increase ones hyper-coagulant state
including infections (especially sepsis where the entire system becomes hyper-coagulant and this can
lead to death), genetic predisposition and drugs (e.g. HRT and oestrogen) all increase clotting.
What increases risk of stasis in veins
Valves in the veins prevent the backflow of blood. Contraction of nearby muscles squashes
veins and acts as a pump tor return blood to the heart. Blood near the valves tends to eddy
around them increasing the risk of stasis (see right).
What happens when venous return is eventually blocked - what is the name for this , risk
If venous return is eventually blocked,
the affected organ becomes congested with fluid increasing the pressure in the vein. This
increases the hydrostatic pressure pushing fluid out of the veins causing oedema. There
can also be some inflammation which amplifies the fluid build-up. This blockage is known
as deep vein thrombosis. The bigger risk is that the thrombus may become dislodged and
make its way back to the heart.
WHat are the fates of thrombus
There are in fact several fates of the thrombus. The first is that the clot can be resolved by
thrombolysis.
This is in fact the fate of many micro-clots that are constantly being formed in our
bodies. The thrombus can sometimes become an embolism which is where it breaks off from the
wall of the endothelium and moves to another location to block that blood vessel (usually a smaller
vessel). This can be very serious depending on where the clot has settled. If it goes to the brain for
example, embolic stroke can occur whilst if it blocks part of the heart, this can also cause a serious
problems.
What can happen if the thrombus is small
If the thrombus is small, it can sometimes become organised which is where the
endothelium grows over it. This is also very common and the effect is the blood vessel is a little
narrower and less elastic, however the consequences of this are minimal.
