Thrombosis Flashcards
How are platelets formed
Megakaryocytes push out structures called pro platelets from their location in the bone marrow into capillaries running through the bone marrow, the platelets then bud off into the blood stream from these structures
What is Hemophilia A and how can this be treated?
This is an x linked bleeding disorder that is due to a genetic defect in coagulation factor 8
This is treated with continual injections of recombinant factor 8
What is Hemophilia B?
This is a mutation in coagulation factor 9 this leads to a bleeding disorder which affects the intrinsic coagulation pathway this is also X linked and can be treated with recombinant factor 9.
What is Von Wille Brand disease?
This is a more common bleeding disorder.
This is due to the type of mutation that can happen you can get mutations that just result in reduced expression which then only leads to you getting a mild form of the disease.
How Is Von Wille Brand disease Treated?
You can use drugs to increase production of VWF
You can treat using recombinant VWF
You can use antifibrinolytics which are drugs that avoid fibrinolysis to push the system to coagulation.
What do the endothelial cells produce to keep the platelets quiescent and what do these molecules do
The platelets produce prostacyclins and also nitric oxide
These work to stop the platelets from sticking to the endothelial surface and they also promote vasodilation of the blood vessel.
What is the main difference between arterial and venous thrombosis?
In arterial thrombosis the endothelial wall of the blood vessel is ruptures but in venous thrombosis the endothelial wall remains in tact.
What are the three main causes of venous thrombosis?
Slow blood flow
Endothelial dysfunction
Altered blood properties leading to increase coagulation chances
What is there an elevated level of in those that present with increase deposition of arterial plaques?
LDL Cholestrol
What are the steps that lead to atherosclerotic plaque formation?
1: LDL particles penetrate the arterial wall across the endothelium by transcytosis or from in between the endothelial cells they then accumulate in the endothelium that lines the wall of the blood vessels.
2: this leads to the formation of a fatty streak in the artery wall
3: the LDLs are oxidised by free radicals
4: the damage to the endothelial cells and the LDL oxidation leads to an inflammatory response and monocytes migrate into the arterial wall as well as T cells
5: The monocytes become macrophages which then ingest the oxidised LDL the accumulation of the LDL turns the macrophages into foam cells in the endothelium
6: smooth muscle cells proliferate and form a fibrous cap around the core of LDL and foam cells this narrow the artery but stabilises the plaque
7: a lot of apoptosis and inflammation can happen the cap thins due to smooth muscle cap thinning
8: then the plaque is prone to rupture which leads to a platelet aggregate that blocks the blood vessel.
What is the common site of arterial thrombus formation?
At the bifurcation of an artery where the laminar flow is disrupted.
How long does it take for blood flow obstruction to cause tissue death?
3 minutes - often when heart tissue dies the heart stops beating entirely.
How often does somebody have a stroke? Heart attack?
Stroke 5 minutes
Heart attack 2 minutes
What is the most common cause of death in the UK
Stroke and heart attack
What are the 6 main causes of arterial thrombosis?
High blood cholesterol Physical inactivity Smoking High blood pressure Obesity Familial predisposition
What does Aspirin do to threat arterial thrombosis?
Inhibits thromboxane a2 produced by activated platelets as a positive feedback mechanism to activate more platelets.
A for aspirin A for A2
What does Clopidogrel do to treat arterial thrombosis?
Blocks the receptor for ADP on the platelet called the p2y12 receptor this blocks the positive feedback mechanism of ADP by platelets.
What are the the two major cell surface receptors that are being looked into for arterial thrombosis treatments?
GP1B receptor for VWF
GP6 for collagen
What is the effect of using alpha2beta3 inhibitors to treat arterial thrombosis?
The integrins are used to stick lots of platelets together using the fibrinogen and VWF as bridges. Drugs can be used to inhibit clotting using this method during operations like stenting but long term use of these drugs leads to severe bleeding problems.
What is the name of the thrombin receptor on platelets that can be blocked to try and limit platelet activation?
PAR1
What is the most common of the anti-platelet therapies?
Aspirin.
What are the three main causes of venous thrombosis?
Slow blood flow
Endothelial cell dysfunction
Altered blood properties leading to increased coagulation.
What is venous thrombosis?
The spontaneous formation of clots.
Inherited:What is factor 5 Leiden?
This Is the most common form of inherited venous thrombosis.
This is when factor five is resistant to activated protein C which normal inhibits factor five by cleaving it, the increased activity of the factor 5 leads to increased chances of clotting happening.
If your heterozygous you’re risk is increases your risk by 5/8X
If you are homozygous this increases your risk by 30/140X
