Haemostasis Flashcards
(37 cards)
Define haemostasis
A precisely orchestrated series of regulatory processes that culminate in the formation of a blood clot that limits bleeding from an injured vessel
What is the purpose of haemostasis?
1) Allows blood to be in a fluid state in normal vessels
2) Formation of a localised haemostatic clot at sites of vascular injury
3) Prevents haemorrhage
What are the 3 components of haemostasis?
1) Vessel wall
2) Platelets
3) Coagulation cascade
What is the layers in a blood vessel?
1) Tunica intima
- Endothelium
- Basement membrane
- Connective tissue
- Internal elastic lamina
2) Tunica media
Circumferentially arranged smooth muscle
3) Tunica adventitia
Connective tissue containing vascular and neural supply
What is the role of endothelium?
Normally endothelium cells are: Antiplatelet, anticoagulant, fibrinolytic.
Acts as a barrier between thrombogenic sub endothelium and coagulation factors in the blood.
Expresses factors which prevent thrombosis in undamaged vessels and limit clot formation to the site of vascular injury.
What is the role of platelets?
1) Form the initial haemostatic plug
2) Provide a surface for recruitment and concentration of coagulation factors
What are the 4 steps in haemostasis?
1) Vasoconstriction
2) Primary haemostasis
3) Secondary haemostasis
4) Clot stabilisation and resorption
Describe what happens in vasoconstriction
- Mediated by reflex neurogenic mechanisms and release of endothelin from endothelial cells
- Minimise blood loss
- Maximises interactions between platelets, clotting factors and vessel wall
What are the 3 stages to the formation of the primary haemostatic plug?
1) Platelet adhesion
2) Platelet activation
3) Platelet aggregation
Describe what happens in platelet adhesion
1) Damage to vessel wall -> exposure of subendothelial matrix
2) von Willebrand Factor (vWF) binds to exposed subendothelial collagen
3) Platelets bind to collagen-bound vWF
4) Platelet adhesion – platelets bind directly to subendothelial collagen
5) Platelets change shape to promote platelet-platelet interactions
Describe what happens in platelet activation
1) Platelets change shape to promote platelet-platelet interactions
2) Conformational change in GPIIb/IIIa receptors
3) Platelet release reaction
4) Platelets also release thromboxane A2 (TXA2)
What is released in the Platelet Release Reaction?
Part of platelet activation in primary haemostasis
Secretory granules release:
- vWF
- fibrinogen
- Calcium (important for forming complexes in secondary haemostasis)
- Serotonin
- ADP
What happens in platelet aggregation?
- ADP and TXA2 promote further platelet aggregation
- Platelet-platelet interact via GPIIb/IIIa receptors and fibrinogen
- Forms primary platelet plug. Not very stable so to stabilise, need secondary haemostasis
What stage of haemostasis is fibrin generation?
Secondary haemostasis
Describe what happens in fibrin generation
1) Damage to vessel wall -> exposure of tissue factor (TF) on subendothelial cells
2) Tissue factor binds and activates factor VII -> coagulation (clotting) cascade!!
3) Thrombin generated -> cleaves fibrinogen into fibrin
4) Fibrin polymerises to form network around plug
5) Forms secondary haemostatic plug
What is the goal of the coagulation/clotting cascade?
To produce thrombin which converts fibrinogen to fibrin, stabilising the clot (secondary haemostasis)
What are the 2 coagulation pathways?
Extrinsic pathway and intrinsic pathway. Both lead to a final common pathway.
Describe the extrinsic pathway
- Measured clinically as prothrombin time (PT)
- Initiated by tissue factor
- Tissue factor is not normally exposed to the blood, it is in the subendothelium – hence extrinsic
1) Exposed tissue factor (TF) converts Factor VII to FVIIa.
2) A complex is then formed containing FVIIa, TF, Ca+
Describe the intrinsic pathway
- Measured clinically as activated partial thromboplastin time (APTT)
- Initiated when FXII comes into contact with a negatively charged surface (eg. An activated platelet) -> FXIIa
FXIIa -> FXIa -> FIXa -> FIXa + FVIIIa + Ca2+ (tenase complex)
The complex from the extrinsic pathway also helps activate FIX
What are the three components of the tenase complex?
FVIIIa, FIXa and Ca2+
What happens in the common pathway?
1) The complex from the extrinsic pathway and the tenase complex activate FX -> FXa.
2) FXa, FVa and Ca2+ form a prothrombinase complex.
3) The prothrombinase complex converts prothrombin (FII) to thrombin (FIIa)
4) Thrombin converts fibrinogen to fibrin
5) Thrombin also activates FXIII to FXIIIa which then converts fibrin into cross-linked fibrin (which is more stable).
What are the three components of the prothrombinase complex?
FXa, FVa and Ca2+
What are the actions of thrombin?
1) Conversion of fibrinogen to fibrin
2) Amplifies coagulation process by further activating:
FXI
FV
FVIII
3) Activates FXIII -> covalent cross-linking between fibrin polymers-> stabilises the secondary haemostatic plug.
4) Further platelet activation
Proinflammatory effects – contributes to tissue repair and angiogenesis
5) Anticoagulant effects – when interacting with normal endothelium -> helps limit clots to site of injury
What are the factors which limit coagulation?
1) Dilution
2) Need for a negatively charged surface provided by activated platelets
3) Anticoagulation factors expressed by adjacent intact endothelium
4) Circulating inhibitors, e.g. antithrombin III – actively augmented by heparin-like molecules on intact endothelium -> inhibits thrombin, FIXa, FXa, FXIa, and FXIIa
5) Fibrinolytic cascade
