3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.4. Physiology
                  3.1.4.4. Haematology
                      3.1.4.4.1. Haemostasis
 3.1.4.4.1.3. Coagulation factors 

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