Coagulation factors

Synthesis of coagulation factors

• All coagulation factors except vWF are synthesized in liver
• vWF is synthesized by endothelial cells and platelets

Factor 2 (Thrombin/prothrombin)

Actions of thrombin

• Catalyse the conversion of fibrinogen to fibrin
• Positive feedback action
  --> Activates factor 5,8,11
• Activates factor 13
  --> Stabilises clot
• Enhance platelet adhesion
• Activation of platelets, endothelial cells, and leukocytes
• Binds to thrombomodulin at intake vessel walls
  --> Activation of protein C and prevents clot formation

Amplication by thrombin

Minute amount is produced during platelet plug formation
--> Thrombin amplifies the platelet plug formation reactions

• Enhance platelet adhesion
• Activates platelets (plus aggregation and release of granules)
  * via PAR receptor (Protease activated receptors)
• Activates factor 5,8,11
  * Thrombin splits vWF-factor 8 complex (bound to platelet surface)
  --> Activating factor 8 and release vWF

Factor 3 (Tissue factor)

aka thromboplastin

An integral membrane protein present in cells around the vascular bed

TF is expressed in the membrane of a variety of extravascular cells (e.g. fibroblasts)

TF is also expressed by blood monocytes and endothelial cells in inflammatory states

Function of tissue factor

• A cofactor for factor 7
• Does not circulate in blood
• Activates coagulation in normal response to vascular injury and in inflammatory states
• Generates trace amount of thrombin
  --> Set up for positive feedback effect of thrombin

Factor 4 (Calcium)

• In vivo, Ca2+ level low enough to interfere with coagulation is incompatible with life
• In vitro, Ca2+ removal can prevent clotting

Factor 7

• Main role seems to be to activate factor 9, rather to activate factor 10 directly
  * [PK1:p249]

Factor 8

• Factor 8 has two components: Factor 8 C and Factor 8 vWF
• Factor 8C is synthesized in liver and inactivated by protein C and protein S
• Factor 8 vWF is synthesized by endothelial cells and platelets
  --> Circulates in blood
• von Willebrand factors binds to factor 8
  --> Regulate the level of active factor 8 (Factor 8C)
• Factor 8 is activated when it is separated from von Willebrand factor [WG21:p545]

Factor 9

• Factor 9 in vivo is considered to be activated mainly by factor 7

von Willebrand factor (vWF)

Synthesized by

• Endothelial cells (stored in Weibel-Palade bodies)
• Megakaryocytes (stored in alpha-granules in platelets)

Main function

• Bind platelets to damaged subendothelium
• Bind activated platelets to each other
  * Fibrinogen may be more important than vWF in this role
• Binds to factor 8
  * Regulation of factor 8a
  * Binding to factor 8 prevents factor 8a from degradation

NB:

• vWF gene is on chromosome 12