Blood coagulation or blood clotting in animals

Blood coagulation or blood clotting in animals

Many substances present in tissue and blood affect coagulation. Substances that promote coagulation are called as procoagulants‚ and those inhibiting coagulation are anticoagulants.

Three stages of clot formation

  1. Formation of prothrombin activator in response to rupture of blood vessel or damage to the blood itself.
  2. Conversion of prothrombin into thrombin by the catalytic activity of prothrombin activator.
  3. Conversion of fibrinogen into fibrin thread by the enzymatic activity of thrombin.

Intrinsic and extrinsic mechanism of clot formation

Intrinsic or endogenous mechanism

When the blood come in contact with foreign surface (other than intact vascular endothelium) like disrupted endothelium, negatively charged surface or glass, it causes a sequence of enzymatic reactions to initiate the coagulation mechanism. Blood drawn in a glass tube clots by this mechanism.

Extrinsic or exogenous mechanism

These sequential enzymatic reactions occur when the blood from the damaged blood vessel contacts extra-vascular tissue factor, the tissue thromboplastin, released from the surrounding tissues. Tissue thromboplastin is not present normally in the blood but released when the surrounding tissue is damaged.

Blood clotting cascade

Most of the clotting factors are inactive proteolytic enzymes and when activated produce enzymatic activities leading to cascading reaction of clotting process.

The extrinsic mechanism is fast acting. The cascade reactions of clotting process involving so many factors helps even a low amount of stimulus (damage) to produce large amounts of final end product (clot).

In the intrinsic mechanism, injury to the blood alters the factor XII and the platelets of the blood. When the factor XII comes in contact with collagen or a wettable surface, it becomes a proteolyt­ic enzyme called activated XII (XIIa).

The blood trauma also damages the platelets, release platelet phospholipid, which is essential for subsequent reactions. In the extrinsic mechanism, the damaged tissue releases a complex of factor called tissue thromboplastin contains phospholipids and a glycoprotein which acts as proteo­lytic enzyme.

Conversion of prothrombin to thrombin

Both intrinsic and extrinsic mechanisms results in the formation of a complex called prothrombin activator complex, which includes activated Factor X, (acts as protease on prothrombin); Factor V (acceler­ates protease activity) and phospholipid (further activates the whole process).

The prothrombin activator acts on prothrombin and converts it to thrombin. The thrombin converts fibrinogen to fibrin monomers. It also activates more and more of Factor V, which further accelerates prothrombin activation.

Clotting factorsProteins except factor IV
Factor IFibrinogen
Factor IIProthrombin
Factor IIITissue thromboplastin
Factor IVCa++ ion
Factor VLabile factor/Proacclerin
Factor VIISerum prothrombin conversion accelerator/Proconvertin
Factor VIIIAntihemophlic factor C
Factor IXChristmas factor/Antihemophlic factor B
Factor XStuart factor
Factor XIPlasma thromboplastin antecedent
Factor XIIHageman factor
Factor XIIIFibrin stabilizing factor
VWFVon Willebrand factor
PrekallikreinFletcher factor
HMWKHigh molecular weight kininogen
Fibronectin 

Prothrombin is a plasma protein, an alphaglobulin (molecular weight 68,700) produced from the liver. Vitamin K is required for the formation of prothrombin and clotting factors VII, IX and X. Thrombin is formed from prothrombin by the action of prothrombin activator and Ca++.

Blood clot formation

Blood clot formation - Blood coagulation or blood clotting in animals
Blood clot formation

Conversion of fibrinogen to fibrin

Fibrinogen is a high molecular weight plasma protein produced from liver. The proteolytic enzyme thrombin acts on fibrinogen and remove 4 low molecular weight peptides from each molecule of fibrin­ogen resulting in formation of fibrin monomer which polymerises with other fibrin monomers and forms fibrin threads.

The fibrin-stabilising factor, present in platelets and to small extent in plasma, causes covalent bonds between the fibrin monomers and cross linkage between adjacent fibrin threads thus adding strength to the fibrin meshwork, the clot.

Clot‚ is composed of fibrin threads running in all directions and entrapping blood cells, platelets and plasma. The fibrin threads adhere to damaged surface of blood vessel and close the opening in the blood vessel thereby prevent blood loss.

Clot retraction: Within a few minutes after a clot is formed, it begins to contract and expresses most of the fluid from the clot within 30 to 60 minutes. The fluid that is expressed out of the clot is called serum.

Platelets are necessary for clot retraction. This is caused by the contraction of actin and myosin of the platelets by using ATP of platelets.

Fate of clot

  • Once a blood clot is formed, it can follow either of the following two courses.
    1. The clot may be invaded by fibroblasts (the formation and invasion is stimulated by platelet derived growth factor) within few hours of its formation. The fibroblasts promote connective tissue formation within the clot and within 7-10 days the clot is organised into fibrous tissue.
    2. When the hemorrhage occur in large quantities and when the blood clot forms in the tissues, some special substances formed within the clot will dissolve the clot (lysis of clot).

Lysis of blood clot

The plasma contain a glycoprotein called plasminogenor profibrinolysin. During the formation of clot, this is trapped within the clot. This can be activated to plasmin or fibrinolysin by tissue plasminogen activator (tPA) released from the damaged tissues and vascular endothelium. The plasmin acts as proteolytic enzyme and digests fibrin threads leading to dissolution of clot.

Scroll to Top