9. Haemostasis 1 Flashcards
Define haemostasasis
The stopping of blood flow
How is coagulation initially stimulated?
Stimulated by vessel injury - there is an exposure of collage and this leads to the ‘platelet release reaction’
The vessel injury also results in the release of tissue factor, which activates the ‘coagulation cascade’
NB. vessel injury also stimulates vasoconstriction to reduce blood flow
Briefly describe the platelet release reaction
Release of serotonin which leads to vasoconstriction
Release of Thromboxane A2 and ADP which results in platelet aggregation
Release of platelet phospholipid which activates the coagulation cascade
SO all the components of anticoagulation are dependant on the platelet release reaction
What is meant by primary haeomostasis and briefly describe this
Primary haemostasis refers to the formation of the primary platelet plug
This occurs due to the platelet aggregation and reduced blood flow created from the platelet release reaction
What is meany by secondary haemostasis and briefly describe this
This is the coagulation cascade
Leads to the formation of thrombin and then fibrin which transforms the primary haemostatic plug into a stable haemostatic plug
I.e. stabilises the primary platelet plug when the plug alone is insufficient to stop the haemorrhage
What is Von Willebrand factor (vWF)?
This is a glycoprotein that circulates in the plasma
vWF is made by cells in the bone marrow and by endothelial cells
Mediates the adherence of platelets to one another and to the sites of vascular damage
Binds to GpIb, GpIX and GpV on the surface of platelets and this activates aggregation of platelets as well as collagen formation
What is Von Willebrand disease?
Autosomal inheritance
Deficient or defective VWF
Means that these patients cannot clot properly and are prone to excessive bleeding
Name two common platelet disorders and they they occur
Bernard Soulier syndrome - lack of GpIb
Glanzmann’s syndrome - lack of GPIIb
What are the three stages of primary haemostasis?
Adhesion
Activation
Aggregation
Give the mechanism of action of primary haemostasis
(Remember primary haemostasis is the formation of the platelet plug)
- Adhesion
Damage to the endothelium exposes the subendothelium
The endothelial cells then release VWF
VWF anchors platelets to the subendoethelium via GpIb binding - Activation
Thrombin combines with it’s receptor on the platelet surface
The platelet then undergoes a shape change
There is a release of thromboxane A2 and ADP from the platelet - Aggregation
TXA2 and ADP uncap the fibrinogen receptor on the platelet
The fibrinogen then attaches to GPIIb/GPIIIA
Platelets are then linked together
A water soluble clot is formed
Describe the importance of tissue factor in secondary haemostasis (coagulation cascade)
Tissue factor is necessary for the initiation of coagulation
It is present on the subendothelial tissue
It comes into direct contact with blood upon trauma
It is factor VII dependent
The tissue factor leads to the activation of coagulation factors in the blood at the site of the injury
What is the roll of fibrin in the coagulation cascade?
Fibrin polymers form long chains between platelets in the primary plug to form a more stable clot
How is fibrin formed?
Coagulation factors adhere to platelets and form catalytic complexes
These complexes cause the formation of thrombin
Thrombin converts fibronogen to fibrin
What are the three pathways of the coagulation cascade?
Intrinsic pathway
Extrinsic pathway
Final common pathway
Give the mechanism of the intrinsic pathway of the coagulation cascade
How is this pathway activated?
Activated by subendothelial collagen exposure from trauma
XII –> XIIa
XI –> XIa
IX –>IXa (using Ca2+)
X –> Xa (using VIII)
