CVS 9: Haemostasis Flashcards
What are the two functions of haemostasis?
- Prevent blood loss from intact vessels
2. Arrest bleeding from injured vessels
What is the first response to vessel wall injury?
Vessel constriction- the smaller blood vessels constrict to stop blood loss
What happens during the primary haemostasis phase?
Formation of an unstable platelet plug
- platelet adhesion
- platelet aggregation
What happens during the secondary haemostasis phase?
Stabilisation of the platelet plug
- blood coagulation
- activation of fibrin
What is coagulation?
The process by which blood is converted from a liquid to a solid state
What is Von Willebrand factor?
It’s a plasma proteins secreted by endothelial cells and platelets
What triggers haemostasis?
- damage to the endothelial lining
- exposure of sub endothelial layer especially the collagen
What are the two ways in which the collagen is recognised?
- Von Willebrand factor binds to collagen and platelets bind to Glp1b receptor on the VWF
- Glp1a on platelets directly binds to the collagen
Why are there two different mechanisms? And under which circumstances will each of the mechanisms be favoured?
Circumstances within the vessels will vary- stressors in blood are different
- Von Willebrand factor= in small blood vessels with high shear stress
What happens once the platelets are activated?
They release ADP and Prostaglandins (Thromboxane in particular)
What is the function of the prostaglandins?
To activate other platelets so the platelets aggregate- Glp2b and Glp3a become available for fibrinogen to bind to
What molecule is generated during the blood coagulation cascade and what is its function?
Thrombin
- directly activates platelets so that they can aggregate
- platelets have specific receptors for thrombin
What happens to activated platelets?
- Changes shape
- Changes membrane composition:
- Phospholipids usually inside the platelet come to the outside
- These phospholipids bind to the coagulation factors
- Platelets present Glp2b and 3a on its surface= can react with fibrinogen
What is the life span of platelets?
8 days
Where are clotting factors, fibrinolytic factors and inhibitors synthesised?
- The liver- most of these made in the liver
- Endothelial cells- Von Willebrand factor is made in high concs
- Megakaryocytes==> Platelets - Factor V is synthesised
What are the two different clotting cascade pathways and what starts of each of the pathways?
- Intrinsic pathway: Factor 12 => Factor 12a
2. Extrinsic pathway: When vessel is damaged, blood comes into contact with TISSUE FACTOR and involves factor 7a
What do the extrinsic pathway and intrinsic pathway merge at?
The common pathway
What is the main driver of coagulation?
Tissue factor > Factor 12
What happens to the haemostat platelet plug once it has been stabilised?
It is fibrinolysed
What is plasminogen converted to and which enzymes does this?
Plasminogen==> plasmin
by Tissue plasminogen Activator (tPA)
The reaction between tPA and Plasminogen does not usually happen, how does it occur then?
The fibrin clot brings the tPA and plasminogen close together on its surface which triggers the cleavage reaction
What is the role of plasmin?
Plasmin is a powerful proteolytic enzyme that can break down the fibrin clot
What are the breakdown products of the fibrin clot? and when might it be measured for diagnostic therapy?
Fibrin Degradation Products (FDP).
Measured when we are giving thrombolytic therapy
What is tPA used to manage in the pharmaceutical industry? Which other enzyme might be used?
tPA and streptokinase (a bacterial activator) used in therapeutic thrombosis for MI
