5. Haemostasis

Question 1

What is haemostasis?

Answer 1

The process of preventing or stopping bleeding in cases of trauma or disease, while maintaining blood in its fluid state (i.e. prevent unnecessary coagulation).

Question 2

Name the major steps in haemostasis.

Answer 2

1. vasoconstriction
2. clot initiation: temporary blockage of vessel damage via platelet plug
3. coagulation: formation of fibrin clot which stabilises platelet plug
4. fibrinolysis

Question 3

What are the essential components required for haemostasis?

Answer 3

1. blood flow - via heart, venous valves and calf pump
2. blood vessels
3. platelets
4. coagulation factors
5. anticoagulant factors

Question 4

How are platelets produced?

Answer 4

Produced in BM by ‘budding’ from megakaryocyte cytoplasm.

Question 5

What is the normal platelet count?

Answer 5

150-400 x 10^9/L

Question 6

What is the normal life span of platelets?

Answer 6

7-10 days

Question 7

Describe the formation of a platelet plug.

Answer 7

1. vasoconstriction (increases delivery of platelets)
2. platelet adhesion
   - damage to vessel wall exposes underlying tissues
   - platelets adhere to collagen fibres in wall via vWF
3. platelet activation
   - secrete ADP, thromboxane and serotonin to become activated and activated other platelets
4. platelet aggregation
   - platelet cross-linking to form plug

Question 8

What is the clotting cascade?

Answer 8

• Amplification system involving activation of precursor proteins to generate thrombin (IIa).
• Thrombin converts soluble fibrinogen into insoluble fibrin.
• Enmeshes initial platelet plug to make stable clot.

Question 9

How is the clotting cascade controlled?

Answer 9

1. natural anticoagulants to inhibit activation

2. clot destroying proteins activated by clotting cascade

Question 10

Name 4 examples of natural anticoagulants.

Answer 10

• protein C (inhibits F5 and F8)
• protein S (stimulates protein C)
• antithrombin (inhibits thrombin (F2) and F10)
• tissue factor pathway inhibitor (inhibits F7)

Question 11

How can activation of the clotting cascade be measured in the lab?

Answer 11

1- APTT (activated partial thromboplastin time) to measure intrinsic pathway. If time required for fibrin clot to form after addition of calcium is prolonged, indicates deficiency in F8, 9, 11 or 12.

2- PT (prothrombin time) to measure extrinsic pathway. If time required for fibrin clot to form after addition of Tissue Factor is prolonged, indicates deficiency in F7.

3- Problems common pathway indicates deficiency in F5, 10, prothrombin and/or fibrinogen.

Question 12

What are the functions of von Willebrand Factor (vWF)?

Answer 12

blood glycoprotein involved in haemostasis

1. platelet adhesion to vessel walls (binds to platelets and collagen)
2. platelet aggregation
3. stabilises and transports factor VIII when inactive in circulation

Question 13

How does vessel wall injury lead to activation of the clotting cascade?

Answer 13

Damaged endothelial cells:

1. expose and release vWF: essential for platelet adhesion and transport/stability of factor VIII
2. expose collage and Tissue Factor: initiates activation of clotting factors

Question 14

What is fibrinolysis and how is this carried out?

Answer 14

The breakdown of a fibrin clot after coagulation.

1. Plasminogen (produced by liver) is proteolytically cleaved to plasmin by tPA (tissue plasminogen activator).
2. Plasmin cleaves fibrin into fibrin degradation products.

Question 15

Describe the role of natural anticoagulants and give examples.

Answer 15

Prevent further coagulation by inhibiting clotting factors.

• Activated Protein C: proteolytically inactivates Factor Va and Factor VIIIa
• Protein S: co-factor to APC
• Anti-thrombin: proteolytically inactivates Factor IIa (thrombin) and Factor Xa