Haemostasis #1 Flashcards
What is haemostasis?
- arrest of blood loss from damaged vessels
- active process that inhib/induces platelet activation
What are platelets like during haemostasis?
- non-adhesive
- circulate singularly
What happens to platelets during vessel wall injury?
- aggregate
- become stabilised by fibrin
- arrest bleeding from severed vessels (clotting)
What is thrombosis?
formation of occlusive thrombi leading to MI, ischaemic stroke
What does NO + prostacyclin (PGI2) do?
- released by endo cell + can inhib platelet formation + sm cell activity
What does EDHF do?
released by endo cell + inhib sm cell activity
What does endothelin 1 (ET-1) do?
released by endo cell + activates sm activity
What does thromboxane (TXA2) do?
released by platelets + activates sm cell activity
Describe activation of platelets + vasoconstriction
- damage to blood vessel
- exposure of platelets to collage + von Willebrand factor in ECM of damaged blood vessel + later exposure to thromboxin
- causes platelets to adhere by adhesion mol to ECM + activate release of mediators
- cause vasoconstriction of blood vessel to stop blood loss + aggregation of platelets
- formation of soft platelet plug
What is the 1st part of the clotting pathway (simplified)?
initiation (used to be extrinsic as TF not normally present on damaged vasculature but becomes expressed when blood vessel damaged)
What is initiation activated by?
tissue factor
Where does initiation take place?
on TF-expressing cells in tissues after blood with clotting factors leaks out of vessels
What are clotting factors?
serine proteases
Describe process of initiation of clotting pathway (simplified)
- TF combines with FVII to prod activated FVIIa:TF complex
- activates FX to cause FXa
- FXa cause prothrombin (FII) to prod thrombin (FIIa)
- thrombin activates platelets which leads to amp + propagation of cascade
What is 2nd part of clotting pathway?
amp + propagation (used to be intrinsic as activated by cells normally found in blood vessels)
What does amp + prop involve?
- initiated by thrombin
- involves activation of many factors: FV, FVIII, FIX, FX
Where does amp + prop take place?
on activated platelets surface
Describe process of amp + prop of clotting pathway (simplified)
- FVa combines with FXa to cause amp of prod of thrombin
2. thrombin causes cleaving of fibrinogen to fibrin on surface of activated platelets to cause irrev clot
What does sev of steps of clotting pathway involve?
Ca2+ + phospholipids
What are key roles of FXa + FIIa?
- accelarate cascade
- anti-coagulant drug targets
Describe process of initiation of clotting pathway (detailed)
- TF in plasma combines with FVII to prod activated FVIIa:TF complex
- FX activated by complex, Ca2+ + phospholipid to cause FXa
- FXa combine with FVa to cause prothrombin (FII) to thrombin (FIIa)
- thrombin activates platelets which leads to amp of cascade
Describe process of amplification of clotting pathway (detailed)
- on platelet surface
1. thrombin activates platelets - changes shape
2. release of FV from alpha granules in platelets to be expressed on platelet surface to give FVa
3. thrombin cleave FVIII-vWF complex to FVIIIa on platelet surface
4. FVIIIa + FVa cause propagation of FIX to FIXa by TF:VIIa
Describe process of propagation of clotting pathway (detailed)
- FIXa combine with FVIIIa:IXa (tenase) on platelet surface
- activates FX to form FXa:Va (prothrombinase)
- cleaved by prothrombin to thrombin
What is effect of prop?
1000x more thrombin than initiation phase - stronger response
