Topic 12: Haemostasis: Coagulation cascade mechanism

Question 1

What should be mentioned in this topic?

Answer 1

• Haemostasis - Central Cascade - Roles of Thrombin - Extrinsic Way of Coagulation - Intrinsic Way of Coagulation

Question 2

Haemostasis

Answer 2

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

Question 3

Central Cascade

Answer 3

Together with the activation of platelets starts the activation of the enzyme system stored in the plasma and partly in the thrombocytes in inactive forms, which causes formation of the fibrin net from the fibrinogen of the plasma, i.e. the coagulation. The coagulation is a result of either an external tissue injury or the repeated enzyme activation caused by the injury of the internal intima, stimulating a last, common enzyme-activating system. This is the Xth coagulation factor. By activating as factor Xa stimulates the prothrombin-thrombin transformation in the presence of an activation complex: factor IV (calcium), factor V-Va fand the thrombocyte phospholipid (TF3) produced by the thrombocytes are activated. Thrombin is able to turn the plasma fibrinogen to a loose fibrin net, (factor Ia). The last step of this common way is when the coagulation factors XIII – XIIIa activated by the thrombin stabilises the formed fibrin net.

Question 4

Roles of Thrombin

Answer 4

Thrombin is the most important enzyme of coagulation and elimination of the clot. When activated it stimulates the primary processes of fast coagulation. It self activates itself making coagulation very effective. Finally, as this enzyme activates, it immediately starts the stimulation of the processes against coagulation, thus it is responsible also for keeping the balance of the coagulation-anticoagulation mechanisms.

Question 5

Extrinsic Way of Coagulation

Answer 5

• Activates in case of external tissue injuries.
• Two important factors:
• Inactive factor VII in the plasma that activates when the plasma enters the tissues
• The VIIa and the tissue factor released from the tissues activate the first member of the common pathway, the factor X - The essence of activation is that with the help of Ca the tissue factor fixes the other members of the cascade to the site of coagulation.
• The Ca , as a glue helps the connection of the negatively charged injured area and the negatively charged protein factors of coagulation.

Question 6

Intrinsic Way of Coagulation

Answer 6

-Microinjuries occur constantly. In case the very smooth surface of the intima turns rough the intrinsic way activates.

• Three components register the roughness of the surface and stimulate the central cascade by exaggerating this effect:
• Plasma factor XII connects to the surface
• It binds a macromolecular protein (kininogen)
• Binds and activates the enzyme (kallikrein) that transforms the factor XII to active XIIa.
• The XIIa transforms the factor XI to Xia and this ends up with the production of an activator complex.

This activator complex contains the active IXa calcium activated VIII and thrombocyte phospholipids..

The genetic lack of factor VIII causes haemophilia A, the lack of the factor IX causes the B-type haemophilia.

Question 7

Central Cascade: (picture)

Answer 7

Question 8

Extrinsic way of coagulation: (picture)

Answer 8

Question 9

Intrinsic way of coagulation (picture)

Answer 9

Question 10

Fibrinolysis, thrombolysis (picture)