Haemostasis Flashcards
Define haemostasis
Body’s physiological response to prevent significant blood loss after vascular injury
List the 4 step process
- Localised vasoconstriction
- Primary haemostasis (platelet plug formation)
- Secondary haemostasis (coagulation)
- Tertiary haemostasis (fibrinolysis)
Describe each step of haemostasis
1st - Reduces blood flow to injury site + retards blood flow
2nd - Plugs breach in blood vessel
3rd - Strengthens + reinforces platelet plug
4th - dissolves clot once blood vessel integrity has been restored
List the 4 events that occur in primary haemostasis
Platelet adhesion + activation
Aggregation + plug formation
What changes occur during platelet activation
- Change shape
- Cytoplasmic granules released
- Increase thromboxane A2
- Activation + expression of GPIIb/IIIa receptors
Agonist - activated platelet GPIIb/IIIa receptors bind to ______ to form _____ with adjacent platelets to form a primary haemostatic plug. This can stop haemorrhage in _____ blood vessels.
Fibrinogen
Cross-bridges
Small
Activated + aggregated platelets form the phospholipid membrane surface for _____
Clotting
What are the 3 pathways of the coagulation cascade?
Extrinsic, intrinsic, common
Major activation of the cascade requires what?
- Very charged phospholipid-rich membrane
- Enzyme
- Substrate
- Cofactor
- Ca 2+
What is the coagulation cascade?
A sequence of enzymatic reactions involving blood borne coagulation factors
What is the final substrate of the cascade?
Fibrinogen
Fibrinogen is converted into ____ by the enzyme ____
Fibrin
Thrombin
Where are the main coagulation factors synthesised?
Liver
Is extrinsic a quick/slow response?
Quick
Is intrinsic a quick/slow response?
Slow
Which tissue factor is exposed at damaged tissue? (extrinsic pathway)
FIII
What does prothrombin FII require for synthesis?
Require vit K for synthesis
In the extrinsic pathway the released TF forms a complex with _____ and _____ which is called the _______. This activates _____ of the ________ and _______ pathway.
Activation of FX leads to the production of ______.
FVII Ca 2+ extrinsic tenase FX intrinsic common thrombin
In the intrinsic pathway, FXII forms a complex with ______ and ______ on collagen, activating _____.
FXIIa activates ____. FXIa activates ______.
HMW kininogen Prekallikrein FXII FXI FIX
The intrinsic tenase activates _____ in the ______ pathway, leading to the production of _______.
FX
common
thrombin
List the steps of the common pathway
- Activation of FX
- Conversion of prothrombin (FII) to thrombin (FIIa)
- Cleavage of fibrinogen (FI) to fibrin (FIa)
- Polymerisation + stabilisation of fibrin polymers by FXIII
The prothrombinase complex converts ______ to ______
prothrombin
thrombin
Give 2 limitations of the coagulation cascade
- Doesn’t explain how blood clots in vivo
- Assumes intrinsic + extrinsic are independently capable of clot formation
Name the 3 steps of the new proposed model
Initiation
Propagation
Amplification
What are the 2 cells required?
TF-bearing cells
Platelets
Describe the 3 steps of fibrinolysis
- Release of plasminogen activators
- Plasmin production
- Clot lysis + release of degradation products
How is regulation of haemostasis achieved?
Combination of multiple endogenous antithrombotic & antifibrinolytic systems
What are the general regulators of haemostasis?
Endothelium Plasma proteins (protease inhibitors)
Why should the fibrinolytic system be regulated?
To ensure removal of unwanted fibrin clots & preservation of fibrin in wounds
How many coagulation factors are there?
12
What determines how coagulation factors are identified with roman numerals?
order of discovery
What is fibrinolysis?
Dissolves and removes fibrin clot
What proteolytic enzyme mediates fibrinolysis?
Plasmin
