Basic Haemostasis Flashcards
What are the functions of haemostasis?
- Prevention of blood loss from intact vessels
- Stop bleeding from injured vessels
Outline the main steps of haemostasis in reponse to injury
- vessel constriction
- formation of unstable platelet plug (platelet adhesion and aggregation)
- stabilisation of plug with fibrin (coagulation)
- dissolution of clot and vessel repair
What are the two main stages of haemostasis and describe them?
primary- formation of unstable plug
secondary - stabilisation
Define coagulation
process by which blood is converted from liquid to solid
Outline the formation of the platelet plug
- endothelial damage exposes the collagen in the subendothelial layer
- collagen is recognised by Von Willebrand factor or glycoprotein 1a receptor
- when the glycoprotein receptors on the platelets are engaged either to the Von Willebrand Factor or directly to the collagen, the platelets become activated
- the platelets will release ADP and prostaglandins (thromboxane)
- thromboxane acts on the surface of the receptor
- prostaglandins activate other platelets so the platelets aggregate - the glycoproteins IIa and IIIb receptors become available which the fibrinogen can bind to
- protease called thrombin gets generated which can also directly activate the platelets so that they aggregate
What is Von willenbrand factor?
A plasma protein made by endothelial cells and platelets. It binds to collagen and attracts platelets. The platelets bind to glycoprotein 1b receptor on the VWF
Where is glycoprotein 1a receptor found?
platelets and directly binds to collagen
What determines which mechanism is used to identify collagen?
- Because the circumstances within the vasculature will vary - the stressors in the blood can be different
- In a small blood vessel there could be very high shear stress which favours the Von Willebrand mechanism
What is the clinical significance of thrombin?
specific receptors for thrombin on the platelets which are therapeutic targets
What happens to the platelet when it gets activated?
- When platelets are activated they change shape and hence its membrane composition
- Certain phospholipids which are usually inside the platelet come to the outside (they bind to the coagulation factors)
- The platelet presents new or activated proteins on their surface (e.g. GlpIIb and IIIa - this becomes an active conformation so it can react with the fibrinogen)
Where are clotting factors, fibrinolytic factors and inhibitors made?
- most made in liver
- VWF made in the endothelium
- factor 5 is made in the megakaryocyte
Describe the intrinsic pathway
- factor 12 (precursor protease called zymogen) is converted to factor 12a
- this converts factor 11 to factor 11a
- this converts factor 9 into factor 9a
- this converts factor 10 into 10a
- factor 8a accelerates conversion of 10 to 10a
is factor 8 a zymogen?
no it is a cofactor
What is a zymogen?
inactive enzyme precursor
Describe the extrinsic pathway of blood coagulation
- vessel damage means blood comes into contact with tissue factor
- tissue factor is a smooth membrane protein not normally in blood
- it initiates the clotting cascade
- it binds to factor 7 and converts it into 7a
- 7a converts 10 into 10a
- 10a converts prothrombin into thrombin
- 5a helps convert prothrombin to thrombin faster
- factor 5a is generated from factor 5 by trace amounts of thrombin
- thrombin converts finbrinogen into fibrin making an insoluble clot
- the clot can be crosslinked by factor 13a so it is stabilised
- tissue factor can also activate factor 9 to 9a when it binds to factor 7