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
What is not normally found in lumen of vas endo?
fibroblasts
Describe process of fibrin deposition of clotting pathway
- fibrinogen expressed on GPIIa/IIIa receptors of activated platelets
- thrombin converts fibrinogen to fibrin + binds to it
- get mesh of fibrin through polym
- thrombin + FXIIIa cause cross-linking of fibrin to cause irrev/stable clot
What is clot retraction?
- red clot size
- clot contracts + dies out to form scar
What is atherosclerosis?
- vulnerable plaque formed in blood vessel with lipid rich core + fibrous cap
- caused by poor diet + lack of exercise
What is fibrous cap of stable plaque?
covers core to limit its size
What happens in unstable coronary artery disease?
- disruption of cap causes localised activation + acc of platelets
What is downstream embolism?
- if dynamic process of thombosis + thrombolysis goes wrong in coronary circ - ischaemia of heart cells which leads to MI/emboli lodged in brain cause stroke
- if in pul circ, cause pul embolism
How is haemostasis dynamic process?
- pathways lead to thrombosis + thrombolysis
- thrombosis = full occlusion of artery’s lumen
- thrombolysis = prevent full occlusion
What is Virchow’s triad?
- predis to thrombosis:
1. lower blood flow (more common in vein)
2. endothelial disturbance/damage (more common in arteries)
3. hyper blood coagulability - stasis if blood - lead to dec blood flow which dilutes coagulation proteins which inc risk of thrombosis
What is arterial thrombosis (white clots) usually ass with?
- atherosclerosis
- large platelet component
Where do white clots form?
at site of vascular injury + disturbed blood flow
How is arterial thrombosis treated?
prophylaxis with anti-platelet drugs
What does arterial thrombosis cause?
MI + 80% strokes
What is venous thrombosis ass with?
- stasis/turbulent flow of blood
- vascular injury following surgery/trauma of vessels
- hypercoaguability of blood
What do red clots contain?
RBC component
What is treatment for venous thrombosis?
pro-phylaxis with anticoagulants
What can venous thrombosis cause?
3rd leading cause of cardiovas ass death which leads to pul embolism
