Session 14: Blood groups

Question 1

Why do we clot?

Answer 1

• Primary haemostasis prevents us from, bleeding
• Sealing vascular defect is an NB immunological
  function
• Intact endothelium maintains an adequate barrier
  between tissue and blood

Question 2

Name the five main factors responsible for haemostasis.

Answer 2

1. Endothelium
2. Platelets and Von Willebrand factor (primary
   haemostasis)
3. Procoagulant
4. Anticoagulants
5. Fibrinolysis

Question 3

Name the three endothelium PROCOAGULANT functions and briefly describe each in terms of vessel damage.

Answer 3

• VASOCONSTRICTION
• endothelium releases endothelin-1 that causes
  vasoconstriction
• vasoconstriction has an immediate effect on blood
  loss and also brings platelets to the walls of the
  damaged vessel
• EXPOSURE OF COLLAGEN
• collagen facilitates the binding of platelets and
  and Von Willbrand factor to injured vessels wall
• platelets are aggregated form a primary haemostatic plug and
  participate in secondary haemostasis
• EXPOSURE OF TISSUE FACTOR
• initiates the coagulation cascade

Question 4

Name the three endothelium ANTICOAGULANT functions and briefly describe each in terms of an intact vessel.

Answer 4

• VASODILATION
• mediated by NO and prostacyclin produced by intact endothelium
• INHIBITS PLATELET AGGREGATION
• NO is a direct inhibitor of platelet aggregation
• “hides” collagen
• expresses CD39 that inhibits aggregation
• INHIBITS COAGULATION CASCADE
• “hides” tissue factor from circulating procoagulants
• houses many anticoagulant proteins and receptors

Question 5

Describe the platelet structure.

Answer 5

• Anucleate
• Glycoprotein receptors that bind fibrinogen, VWF, and
  the vessel wall
• Internal structure made of contractile protein and
  granules

Question 6

What is the function of the platelet?

Answer 6

Formation of primary haemostatic plug at side of vessel damage, achieved through:
* adhesion
* aggregation
* release reactions and 
  amplifications

Question 7

Describe the process of adhesion in the functioning of platelets.

Answer 7

- VWF adheres to exposed 
  collagen 
- Platelets bind to VWF via 
  GPIb receptor 
- Platelets adhere to 
  damaged vessel wall 
- Binding of VWF to 
  platelets activates 
  platelets 
  to perform further 
  functions 
- Platelets undergo shape 
  changes called platelet 
  spreading
- Increases the platelets SA

Question 8

Describe the 3 functions of the Von Willebrand Factor.

Answer 8

- Involved in platelet 
  adhesion to collagen 
- Involved in platelet aggregation 
- Carries and extends the 
  half-life of factor VIII

Question 9

Describe the aggregation process in the functioning of platelets.

Answer 9

- Activated platelets 
  upregulate GPIIbIIIa 
  receptors  
- GPIIbIIIa receptors bind 
  fibronogen/VWF then bind 
  to other platelets= 
  aggregration 
- Fibronogen and VWF 
  bridge between platelets 
  and GPIIbIIIa receptors

Question 10

Describe release reactions and amplification in the functioning of platelets.

Answer 10

- Once activated, platelets 
  are triggered to release 
  granule content 
- The granule content is 
  involved in further auto- 
  activation
- Additional platelets 
  accumulate, become 
  activated and adhere to 
  each other

Question 11

Discuss the platelet plug.

Answer 11

- Sufficient to immediately 
  seal vessel damage
- Not stable, needs 
  reinforcement
- Reinforced  by fibrin

Question 12

Describe coagulation.

Answer 12

* Coagulating factors are 
  precursor proteins 
* When needed, they're 
  activated in a sequential 
  cascade and controlled by 
  a negative feedback 
* Cascade culminates 
  generation of thrombin 
* Thrombin converts 
  fibrinogen to fibrin
* Fibrin enmeshes 
  aggregated platelets and 
  converts unstable platelet 
  plugs to stable 
  haemostatic plug

Question 13

Name the 2 types of cascade models and where they’re used.

Answer 13

1. Laboratory-based cascade
   (old)
2. Cell-based cascade (new)

Question 14

Explain how regulators of coagulation (anticoagulants) work.

Answer 14

- Natural anticoagulants 
  regulate extent to which 
  coagulation occurs 
- Assures coagulation 
  doesn't progress beyond 
  damaged site/ becomes 
  pathological thrombosis 
- If clotting switch is "on", 
  anticoagulation switches 
  are "off"

Question 15

Define fibrinolysis and its importance.

Answer 15

Definition: process of removal of fibrin meshwork

Importance: tissue remodeling and restoring vessel patency

• complex balance between initiators and inhibitors
• fibrinolysis and its protein roll players act w/ fibrin to perform its function- fibrin orchestrates its own destruction

Question 16

What are fibrinolysis breakdown products called?

Answer 16

fibrin degradation products (FDP)

* there’s a diff. between crosslinked and non-crosslinked fibrin breakdown