Blood Coagulation, Platelet Aggregation, Fibrinolysis Flashcards
What is haemostasis
The balance between clotting and bleeding.
The balance between normal blood flow and preventing blood loss.
Complex interaction between:
Blood vessels - vascoconstricion
Platelets
Coagulation and clotting factors - inhibitors
Fibrinolysis
What is an embolous
A fragment or whole thrombus that detached from the vessel wall and travels through the vessel. It can block small blood vessels in the pulmonary/ cardiac/ CNS circulation.
What does an embolous cause
Pulmonary embolism
Myocardial infarction
Stroke
How does a thrombus form
When there is not enough blood/ oxygen flow to a tissue the fibrin framework incorporates platelets or other blood cells and they become trapped. It is attached to the vessel wall which then impacts on blood flow and reduces tissue perfusion.
What are the types of thrombus
Venous thrombosis- where coagulation has a major role
Arterial thrombosis- where platelet aggregation plays the major role (coagulation included)
How do you modify a thrombosis
. Modify coagulation (v)
. Modify platelet aggregation (a)
. Modify clot thrombous break down- after prevention fails
What is an example of an anti- coagulant
Parin
Heparin.
We have a natural supply.
It is present in the liver lungs and mast cells as a natural anticoagulant.
VENOUS
What does heparin do
. Activated AT
. AT forms complexes with activated clotting factors (thrombin factors xa) and inactivated them.
. Heparin then increases the rate of complex formation
. Stops thrombous
What are the issues with heparin
It’s poorly absorbed when administered orally but can be given intravenously or subcutaneously.
There is a risk of haemorrhage- when mild stop when severe protea mine sulphate needed to stop heparin AT effect
What is an example of a drug that is an oral anticoagulant
Warfarin.
What does warfarin do
.Related in structure to vitamin K.
.Antagonises vit k’s role in formation of various clotting factors (2,7,9)
.stops conversion of precursors of these to active factors- promotes coagulation.
What are the problems with warfarin
It's slow to work- 3 days Need to give heparin first to work. Variation in half life between clotting factors. Influenced by vit k It interacts with many things Monitored using INR (h/w) Risk of haemorrhage (m stop s vit k/ clotting f/ blood) Teratogenic (avoid preg)
What is rivaroxaban
. Oral fxa inhibitor
. Prevents both venous and arterial thromboembolic disorders
What are the benefits of rivaroxaban
. Fixed dose
. No need for routine monitoring
. Effective in both venous and arterial thromboembolic disorders
. Potentially can replace warfarin
What is dabigatran
.An oral thrombin inhibitor
. Used to prevent venous thrombosis in orthopaedic surgery without increasing bleeding risk
What are the benefits of dabigatran
. Fixed dose
. No routine monitoring
. Effective in preventing venous thrombosis in orthopaedic surgery with no increased risk of bleeding
. Potentially replace warfarin
How does a clot form
Damage to the vessel
Then collagen is exposed
The platelets then bind and are activated
There’s an increase in txa2 synthesis
This leads to an increase in GPIIB / IIIA receptor expression on the platelets
The platelets hen aggregate
What factors affect aggregation
. Synthesis of a thromboxane in platelets (reduce)
. cAMP levels in platelets (increase)
. Glycoprotein IIb IIIA receptors in platelet (reduce)
What is an example of an anti platelet drug which reduces synthesis of thromboxane within the platelets
Asprin
What does Asprin do
. Blocks COX enzyme to reduce txa2 synthesis.
. Aggregation is reduced until new platelets are made. 7-10.
. Low dose needed to avoid enzyme endothelium.
. Alters the balance between platelet txa2 and endothelial PGI2
What is an example of an anti platelet drug which raises cAMP levels in the platelet
Dipyridamole
What does dipyridamole do
. Stops PDE enzyme . Prevents cAMP breakdown in platelets . Decreases platelet aggregation . Blocks he intake of adenosine into platelets, red cells and endothelial cells . Stops TXA2 synthesis
What is an example of a drug which reduces the glycoprotein IIb/ IIIa receptors in a platelet
Clopidogrel
How does Clopidogrel work
. Inhibits platelet receptors
. It’s irreversible and specific
. It stops ADP receptor
. It blocks the activation of glycoprotein IIb/IIIa pathway