Haemostasis

Question 1

Primary haemostasis - Platelet plug

Answer 1

Initial response

Compounds:
- Platelets
- Von Willebrand Factors (VWF)
- Collagen

1. Damage exposes collagen and releases VWF
2. Causes platelet adhesion at site of injury
3. Platelets secrete chemicals leading to aggregation of platelets at site of injury

Question 2

Secondary haemostasis - Fibrin clot

Answer 2

Vitamin K dependent coagulation factors

1. TF > Factor V
2. Factor V allows Prothrombin > Thrombin
3. Thrombin allows Fibrinogen > Fibrin
4. Thrombin releases factor VIII which can make more Factor V allowing reaction to repeat

Question 3

Fibrinolysis

Answer 3

1. Plasminogen > Plasmin via tissue Plasminogen Activator (tPA)
2. Plasmin breaks down Fibrin > FDPs (fibrin degradation products)

Question 4

Positive and negative feedback loops:

Answer 4

Maintain balance

Some overlap
Complex systems

Negative:
- Protein C inhibits FV and FVIII
- Protein S - Co factor that helps platelets bind
- Antithrombin - Binds to FX and Thrombin
- TFPI

Question 5

What is haemostasis:

Answer 5

Vasoconstriction

Physiological process to stop bleeding, prevents blood loss, and maintain blood vessel integrity

Question 6

Anti platelet treatment for arterial disease:

Answer 6

Anti-platelet drugs:
- Inhibit platelet function therefore primary haemostasis

Arterial thrombosis:
- Atherosclerosis
- Platelet rich thrombus

Treatment:
- Aspirin: Inhibits COX 1, decreasing thromboxane production

P2Y12 Receptor:
- GCPR for ADP
- Decreases cAMP levels

Question 7

Anticoagulation for venous disease:;

Answer 7

Anticoagulants:
- Inhibits fibrin clot formation
- Treats venous thrombosis and AF

Venous thrombosis:
- Virchow’s triad: Stasis, Vessel wall, Hypercoagubility

Treatment:

Heparin (Unfractionated):
- Potentiates effects of antithrombin
- Rapid onset of action but a short half-life
- IV administration

Heparin (low molecular weight)
- As effective as UFH
- Longer half life
- Lowe risk
- Subcutaneous administration

Warfarin:
- Inhibits Vitamin K OR (can cause bleeding)
- Monitored by INR (international normalised ratio)
- INR = Patients pt (s) / Mean normal PT (s)

Question 8

Treatment based on patient and disease specific factors:

Answer 8

Direct oral anticoagulants:
- Single dose
- No monitoring
- Safer

Andexanet-Alfa (reverses direct oral anticoagulants):
- E.g. Edoxaban
- Modifies FX
- Short half life

Idarucizumab:
- E.g. Dabigatran
- Thrombin inhibitor
- Monitored
- 13h half life

Tranexamic acid:
- Anti-fibrinolytic