Topic 11 - Haemostasis (except coagulation cascade mechanism) and stopping blood coagulation

Question 1

Words to include

Answer 1

• Defense reaction
• Internal vessel injury
• External vessel injury
• Hemophilia
  
  • Coagulation (ø)
• Thrombus
  
  • Over-reaction of coagulation
• Steps:
  
  • Injuries (continuous internal, casual external)
  • Vascular reaction
  • Thrombocyte reaction
  • Coagulation cascade mechanism
  • Fibrinogen-fibrin transformation
  • Formation of white or red thrombus
  • Blood loss ceases
  • Vascular reaction decreases
  • Inactivation of the cascade
  • Fibrinolysis
  • Thrombolysis
  • Reparation of the vessel walls
  • Complete local healing

The balance system

• Capillary injury
• Intrinsic way of hemosatis
• Self-inhibiting mechanism
• Balance system
  
  • Continous internal and external injuries
  • Continous hemostatic, clot forming mechanisms
  • Continous clot-removing mechanisms
  • Continous local healing
• Imbalance
  
  • Thrombosis
    
    • Clot forming mechanism ↑
    • Clot removal ↓
  • Hemophilia
    
    • Local healing ↓
    • Damaged local healing

Vascular reaction

• Automatic process
• Mechanical defense
• Perfusion ↓
• 6-10 min
• First line of defense
• Steps:
  
  • Injury of smooth mucle cells
  • Membrane potential
  • Potential difference
  • Reflex contraction
  • CNS-activation
  • Humoral vasoconstrictor substances
• Contraction after injury
  
  • Direct depolarization of smooth muscle cells
  • Neural: reflex
  • Tissue vasoconstrictor factors
  • Vasoconstrictors form platelets:
    
    • Serotonin
    • TX2 (Thtromboxane A2)
  • Perfusion drop

Thrombocyte reaction

• Thrombocytes = platelets
• Secretion
  
  • White thrombus
• Steps:
  
  • Intima injury
  • Primary activation:
    
    • Platelets binds to the exposed collagen
  • Von Willebrand factor increases primary activation
  • Secondary activation
  • Thrombocytes bind together
    
    • Secrete coagulation factors
  • Production of the endothelial PG_I2 and NO stops
  • Secretion of thrombocytes
  • Thrombin forming in the meantime activates
  • Thrombocyte released:
    
    • 5-HT (serotonin)
    • ADP
    • PF-3
    • TXA2 (thromboxane A2)
    • Coagulation factors

Stopping blood coagulation

• Over-reaction
• Anticoagulation
  
  • Endothelial cell
  • Thrombin
  • Plasma protein
  • Protein-C
  • Calcium
  • Intrinsic and extrinsic activation complex
    
    • Factor V
    • Factor VII
• Fibrinolysis
  
  • Thrombin
  • Plasma protease
  • Plasminogen
• Thrombolysis
  
  • Loosening of clot
  • Phagocytosis
  • Thrombus
  • Perfusion ↑

Question 2

Topics to include in the essay

Answer 2

1. Introduction of hemostasis
2. Steps of hemostasis
3. The balance system
   
   • Imbalance (hemophilia, thrombus)
4. Vascular reaction
5. Thrombocyte reaction
6. Stopping blood coagulation
   
   • Anticoagulation
   • Fibrinolysis
   • Thrombolysis

Question 3

What is haemostasis?

Answer 3

Haemostasis is a complex defense reaction which prevents the loss of blood in case on internal or external vessel injury

Question 4

Give the steps of haemostasis

Answer 4

1. Injuries (continuous internal, casual external)
2. Vascular reaction
3. Thrombocyte reaction
4. Coagulation cascade mechanism
5. Fibrinogen-fibrin transformation
6. Formation of white or red thrombus
7. Blood loss ceases
8. Vascular reaction decreases
9. Inactivation of the cascade
10. Fibrinolysis
11. Thrombolysis
12. Reparation of the vessel walls
13. Complete local healing

Question 5

The balance system

Answer 5

• In a physiological environment capillary injuries constantly occur due to everyday mechanical activities. Therefore the intrinsic way of the hemostasis is constantly working together with a self-inhibiting mechanism
• This balance makes sure that the aggressive coagulation mechanism does not lead to pathological clot-formation

Imbalance

• Hemophilia (bleeding sickness, lack of coagulation)
  
  • Local healing ↓
  • Damaged local healing
• Thrombosis (pathological clot formation, over-reaction of coagulation)

Question 6

Vascular reaction

Answer 6

• First line of defense, occurs right after injury
• Automatic process
• Temporary stage: 6-10 minutes
• Tasks of vascular reaction:
  
  • Mechanical defense
  • Decreasing of the perfusion
    
    • Result: thrombocytes can stick to the injured surface more easily, basis of further reactions
• Steps:
  
  1. Injury of smooth muscle cells → membrane potential of the injuried cells will be different from that of the surrounding cells → contraction of the surrounding smooth muscle cells
  2. Reflex contraction, caused by CNS-activation
  3. Humoral vasoconstrictor substances released from the injured cells
• Contraction after injury:
  
  • Direct depolarization of smooth muscle cells
  • Neural: reflex
  • Tissue vasoconstrictor factors
  • Vasoconstrictors form platelets:
    
    • ​Serotonin
    • TXA2
  • Drop in perfusion
    
    • ​Optimal condition for the accumulation of platelets

Question 7

Thrombocyte reaction

Answer 7

• Thrombocyte = platelets
• Thrombocytes do not attract to intact endothelial cells
• Secretion: white thrombus

Steps:

• Intima injury
• ​Primary activation:
  
  • The platelets binds to the exposed collagen
    
    • Von Willebrand factor increases primary activation​
• Secondary activation starts
  
  • Actin, microtubule system of the thromobcyte and their secretions activates the reaction
  • Thrombocytes bind together due to fiopodia, secrete coagulation factors
    
    • ​White thrombus is formed
  • Vascular endothel produces:
    
    1. Prostacyclins (PGI₂)
    2. Nitrogen monoxide (NO)
  • PGI₂ and NO prevent the production of the factors responsible for aggregation (eg. TXA2)
  • Thrombocytes can therefore produce their own stimulating factors:
    
    1. TXA2 (thromboxane A2)
    2. Serotonin
    3. ADP

Question 8

Stopping blood coagulation

Answer 8

• The inhibition of over-reaction of the coagulation mechanisms and the elimination of the formed thrombus in time are supported by an anticoagulative, fibrinolytic, and thrombolytic system activated at the beginning of the coagulation process
• Anticoagulation:
  
  • _​_Endothelial cells bind to thrombin
  • Thrombin activates protein-C (plasma protein) with the help of calcium
  • The active protein-C prevents the activation of the key enzymes of the intrinsic and extrinsic activation complex
    
    • ​Factor V
    • Factor VII
• Fibrinolysis
  
  • ​The thrombin stimulates the activation of plasminogen (inactive plasma protease)
• Thrombolysis
  
  • ​Decreasing the size of the thrombus:
    
    • ​Loosening of clot
    • Phagocytosis starting from the inside
  • Increasing perfusion plays a role in the demolition of the thrombus