Haemostasis Flashcards
What is hameostasis?
The cessation of blood loss from damages vessels by a specific sequence of responses
What are the 4 phases of haemostasis?
Not linear, all occur at the same time
1) Vascular phase (occurs immediately)
2) Platelet phase (inv. the platelet plug)
3) Coagulation phase
4) Tissue repair and clot breakdown (fibrionolysis)
What occurs during the vascular phase?
Vascular spasm and changes to the endothelial cells
What is vascular spasm?
- Contraction of the smooth muscle by a nerve impulse
- Occurs immediately and lasts for several hours
- Constricts the diameter of the lumen, in order to lose less blood
What vessels is vascular spasm specific to and why?
Arteries and arterioles as they have smooth muscle
What are the 3 changes that occur to the damaged endothelial cells?
1) Contraction - exposing the basal lamina and collagen underneath the cells to the blood
2) Release chemical factors
3) Become more adhesive - helps the platelet plug
What chemical factors do damaged endothelial cells secrete and what do they do?
- ADP: Platelet aggregation
- Tissue factor (FIII): extrinsic pathway of coaggulation
- Prostacyclin: reduces the spread of platelet aggregation
- Endothelins: peptide hormone
1) Stimulate smooth muscle contraction aftet the nerve impulse
2) Promotes cell division
How does prostacyclin reduce the spread of platelet aggregation?
- They are reduced where the damage is
- They are increased either side of the damage
What are platelets?
Anucleate fragments, essential for clotting
How long do platelets last?
Around 10 days
What is thrombocytopoiesis and how does it occur?
Platelet production
- Megakaryocytes send projections into the bone marrow sinuses and shed cytoplasm in small, membrane-enclosed packets (platelets)
Where are platelets made?
In the bone marrow by megakaryocytes
What is the platelet phase dependant on and when does it occur?
Temperature dependant
Occurs 15 seconds from injury
What are the 3 stages of the platelet phase?
1) Platelet adhesion
2) Platelet activation
3) Platelet aggregation
What happens during platelet adhesion?
Platelets stick to the damaged part of the blood vessel (eg. exposed collagen):
- Collagen expresses ‘Von willwbrand factor’
- Platelets have receptors
This activates the platelets
What happens during platelet activation?
- Platelets change shape (swell and have spike extension)
- Granulolysis (release of 2 types of vesicles)
What does granulolysis of platelets release and what does this do?
- ADP : stimulate aggregation and secretion
- Serotonin and thromboxane A2 (vascular spasm)
- Clotting factors (eg.PF3)
- Platelet derived growth factor: promote vessel repair
- Ca2+ : Aggregation and clotting
What type of feedback is used in granulolysis?
Postivite feedback
- More activated platelets
- More granulolysis
- More platelets brought in and activated
What happens during platelet aggregation?
- The positive feedback loop forms a platelet plug (from build up of platelets)
- This covers the whole area of damage
What is platelet aggregation stimulated by?
ADP
TA2
Ca2+
Positive feedback
Where is the platelet plug restricted to and how?
The site of injury
Inhibited by:
1) Prostacyclin and NO (nitrous oxide) released from the intact endothelium
2) Compounds released from blood vessels
3) Aspirin
When does coagulation occur?
30 seconds after injury
What are the 4 aims of coaggulation?
1) Make small platelet plug into a blood clot
2) Convert circulating fibrinogen into insoluble fibrin
3) Promote growth of fibrin network to cover the platelet plug
4) Trap passing blood cells within this network to form a blood clot
How is fibrinogen converted into fibrin?
1) Prothrombinase converts prothrombin into thrombin
2) Thrombin converts fibrinogen into fibrin
This way thrombin is not always making fibrin
Why must fibrin have a precursor?
- Fibrin molecules stick to eachother, so can’t have it circulating in the blood
- Instead have soluble precursor fibrinogen
What does the coagulation phase trigger?
A cascade of enzyme reactions to make fibrin (AMPLIFICATION)
What are the 3 pathways of coagulation and what stimulates them?
1) Intrinsic pathway
- Stimulated when collagen triggers activation of proenzymes
- Produces the majority of thrombin (which can activate the pathway more- feedback)
2) Extrinsic pathway
- Begins with the release of FII from damages tissue
- Occurs immediately
- More damage = more released = faster clotting
3) Common pathway
- Triggered by release of factor X from 1) and 2)
Apart from making fibrin, what else does thrombin do?
- Causes release of more tissue factor and PF3 (clotting factor)
- Produces anti-thrombin (negative feedback)
After blood clotting what must happen?
- Blood clot needs to contract to pull the 2 edges of the blood vessel together
- Need to break down the clot
- Then the tissues can repair themselves
What wold too much clotting cause?
A thrombus
What substances restrict clot formation, how? Where are they released from?
1) Anti thrombin III
2) Heparin: accelerates ATIII activation, resticts clot
- From intact endothelium
3) Thrombomodulin: convets thrombin to another enzyme
- From thrombin
4) Prostacyclin: restricts aggregation
- From intact endothelium
5) Medicines (Aspirin and warfarin)
What is wound healing and fibrinolysis stimulated by and what does this cause?
Production of thrombin
- Thrombin and t-Pa (tissue plasminogen activator) activates plasminogen
- Plasminogen froms plasmin (enzyme that degrades fibrin strands)
What is deep vein thrombosis?
- An inherited, anti-thrombin deficiency
- Can’t break down the clot
OR from staying still
What is vitamin K needed for?
What can reduce it?
Needed to synthesise clotting factors in the liver
- Antibiotics can reduce it
How is the liver involved in heamostasis?
Synthesises and clears clotting factors, coagulation inhibitors and fibrinolytic agents
What are 2 diseases of the liver which disrupts clotting?
Hepatitis
Cirrhosis
What is haemophillia and what 3 things cause it?
Abnormal or absent clotting
1) Deficiency in factory VIII (X linked)
2) Deficiency in facctor IX (X linked)
3) Deficiency in factor XI (Autosomal recessive)
All in the intrinsic pathway
XI activates IX
What is von Willebands disease?
Less clotting as the platelet plug can’t form
VWF helps in platelet activation
