8. MECHANISM OF BLOOD CLOTTING

Blood coagulation (or blood clotting) is the process by which blood from its liquid state changes to a gel-like consistency. A host defence mechanism known as haemostasis is a complex process which blocks the bleeding from a damaged vessel. Platelet adherence and aggregation to macromolecules in the sub-endothelial tissues forms a primary haemostatic plug.

Blood clotting is the most powerful homeostatic mechanism of the body. It is a biochemical reaction carried out by 13 different blood coagulation clotting factors:

SequenceName and Characteristics
Factor IFibrinogen
Factor IIProthrombin
Factor IIITissue thromboplastin or platelet factor-3
Factor IVCalcium (Ca²⁺)
Factor VLabile factor or proaccelerin or Ac-globulin
Factor VIAccelerin or autoprothrombin
Factor VIIStable factor or proconvertin
Factor VIIIAntihemophilic factor-A or antihemophilic globulins or platelet cofactor or thromboplastinogen
Factor IXChristmas factor or platelet cofactor I or plasma thromboplastin or antihemophilic factor-B
Factor XStuart factor
Factor XIPlasma thromboplastin antecedent or antihemophilic factor-C
Factor XIIHageman factor or surface factor or clot promoting factor
Factor XIIILaki-Lorand factor or fibrin stabilizing factor

Under normal conditions, blood circulates in vessels and does not clot spontaneously. Blood coagulation occurs when there is: 1) Trauma or injury to the vascular wall or adjacent tissues, 2) Trauma to blood, or 3) When blood comes in contact with damaged endothelial cells or collagen or other tissue elements outside blood vessels.

Prothrombin activator is formed by two different pathways:

Initiated by trauma to vascular wall or tissues outside blood vessels.

  1. Release of Tissue Thromboplastins: Damaged tissues release tissue thromboplastin (factor III).
  2. Activation of Factor X: Tissue thromboplastin (factor III) combines with stable factor (factor VII) to form tissue thromboplastin-factor VII complex, which in presence of Ca²⁺ activates factor X to Xa.
  3. Formation of Prothrombin Activator Complex: Activated factor X along with labile factor (factor V) and Ca²⁺ (factor IV) forms prothrombin activator.

Initiated by injury to blood itself or exposure of blood to collagen of injured vascular endothelium.

  1. Injury activates factor XII to XIIa; platelets are activated to release phospholipids.
  2. Factor XI is activated to XIa by activated factor XII.
  3. Factor IX is activated to IXa by activated factor XI in presence of Ca²⁺.
  4. Factor X is activated to Xa by activated factor IX in presence of activated factor VIII, Ca²⁺, and phospholipids.
  5. Activated factor X along with phospholipids, activated factor V, and Ca²⁺ forms prothrombin activator (prothrombinase).

Prothrombinase in the presence of Ca²⁺ converts prothrombin to thrombin at the surface of platelets, forming a platelet plug at the injury site.

  1. Thrombin acts as a proteolytic enzyme and converts fibrinogen to fibrin monomer.
  2. Fibrin polymerizes to form a long chain, creating a reticulum of clot.
  3. In presence of fibrin stabilizing factor (factor XIII), covalent cross-linkages form between fibrin threads, covering injured blood capillaries within 2-8 minutes.
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