Haemostasis Flashcards
What is Haemostasis?
Stop blood loss.
Facts about haemostasis:
1) Is it vital?
2) Is it an active or passive process?
3) Why is it a dynamic process?
1) Vital for life
2) Active process - it can activate or inhibit platelet activation.
3) Can induce thrombosis or thrombolysis
Role of platelets in haemostasis:
- In rest state
- In activated state (damaged vessels)
During rest state, platelets are non-adhesive and circulate singularly.
In response to damaged vessels, platelets are activated and aggregate (stabilised by fibrin) to prevent blood loss from severed vessel.
What is thrombosis:
What are its implications (i.e. negative effects):
Thrombosis - formation of a thrombus (blood clot).
Occlusive thrombosis can lead to MI and ischaemic stroke.
What is the vascular control of platelet function?
- NO and PGI (prostacyclin) released from vascular ECs can inhibit platelet activation at rest
- ECs release NO, EDHF and PGI to inhibit SMC contraction
- Platelets release thromboxane which promotes SMC contraction
Initial soft-platelet plug formation in Haemostasis:
1) Damaged vessel causes platelets to be exposed to collagen and vWF in ECM and is later exposed to thrombin
2) That causes activation of platelets allowing them to adhere to the ECM via adhesion molecules
3) Release mediators such as thromboxane - vasoconstriction and aggregation of platelets
4) Form soft-platelet plug and causes haemostasis (initial response)
The clotting cascade (secondary response to haemostasis):
This consists of the extrinsic and intrinsic pathway which both promote activation of FXa (prothrombinase) which converts prothrombin to thrombin.
EXTRINSIC PATHWAY:
1) TF-expressing cells (fibroblasts and monocytes) aren’t always found in vasculature but damaged vessel causes them to be found in the lumen.
2) These release clotting factors (serine proteases) which activate via sequential cascade.
3) TF released from ECs and extravascular space combines and activates FVII.
4) TF:FVIIa activates FX (to FXa) using calcium and PLD.
5) FXa combines with FVa - prothrombinase.
6) Prothrombinase converts prothrombin (FII) to thrombin (FIIa) using calcium and PLD.
INTRINSIC PATHWAY:
7) Thrombin activates platelets and causes them to undergo morphological changes and activates 5 odd-numbered factors from FV: 5, 7, 8, 11, 13.
8) Thrombin causes FV to be released from α-granules of activated platelets and is expressed on cell surface as FVa. (PROPAGATION)
9) Thrombin cleaves vWF-FVIII on cell surface causing FVIII to be activated (FVIIIa). (PROPAGATION)
10) FVIIIa combines with FIXa (TF:VIIa and FXIa (activated by thrombin) activates FIX to FIXa) - forms tenase.
11) Tenase activates FX to FXa which combines with FVa to form more thrombin. (AMPLIFICATION)
FIBRIN DEPOSITION:
12) Thrombin cleaves fibrinogen (FI) (expressed on GPIIa/b on platelets) to fibrin (FIa).
13) Using calcium, polymerisation of fibrin occurs.
14) Thrombin and FXIIIa (activated by thrombin) causes cross-linking of fibrin polymers to allow a stable irreversible clot to form. HAEMOSTASIS!
What type of patients are susceptible to arterial thrombosis:
Patients with atherosclerosis are more susceptible to thrombosis.
Risk factors of atherosclerosis:
- Poor diet
- Lack of exercise
Stable and Unstable Coronary Artery Disease:
Stable:
- plaque formation occurs in major arteries
- has stable lipid-rich core
- has fibrous cap which restricts size plaque
Unstable:
- disruption of fibrous cap
- causes localised activation and aggregation of platelets
Complication of improper arterial and venous thrombus formation:
This can lead to formation of an embolus which circulates in blood and can block arteries in heart, brain or lungs, leading to MI, stroke or pulmonary embolism.
Virchow’s Triad (SHE):
1) Stasis of blood flow
2) Hypercoagulability
3) Endothelial Dysfunction
Low blood flow (common in veins) or endothelial dysfunction (common in arteries) or hypercoagulability (which some individuals are susceptible to) can lead to thrombus formation.
Arterial Thrombosis:
1) What condition is it usually associated with?
2) What sites are they found at?
3) White or Red clot
4) Complication
5) Treatment
1) Usually associated with atherosclerosis
2) Found at site of vascular injury/disturbed blood flow
3) White clot - major platelet component
4) Complication: MI and Stroke
5) Treatment: anti-platelet drug
Venous Thrombosis:
1) What sites are they found at?
2) White or Red clot
3) Complication
4) Treatment
1) Usually found at site of hypercoagulability, stasis/turbulent blood flow, vascular damage from surgery/trauma
2) Red clot - platelet, fibrin and RBC component
3) Complication: Pulmonary embolism
4) Treatment: anti-coagulant drug
Antiplatelet Drugs:
- Purpose of antiplatelet drugs:
- Types of antiplatelet drugs:
Purpose of antiplatelet drugs:
1) Reduces growth and risk of arterial thrombosis
2) Prevents activation and aggregation of platelets and hence thrombus formation
Types of antiplatelet drugs:
1) Aspirin
2) P2Y12 Receptor antagonist
3) GPIs (GPIIβ IIIα receptor antagonist)
