Blood clot is defined as the mass of coagulated blood which contains RBCs, WBCs and platelets entrapped in fibrin meshwork. RBCs and WBCs are not necessary for clotting process. However, when clot is formed, these cells are trapped in it along with platelets. The trapped RBCs are responsible for the red color of the clot. The external blood clot is also called scab. It adheres to the opening of damaged blood vessel and prevents blood loss.


After the formation, the blood clot starts contracting. And after about 30 to 45 minutes, the straw-colored serum oozes out of the clot. The process involving the contraction of blood clot and oozing of serum is called clot retraction. Contractile proteins, namely actin, myosin and thrombosthenin in the cytoplasm of platelets are responsible for clot retraction.


Lysis of blood clot inside the blood vessel is called fibrinolysis. It helps to remove the clot from lumen of the blood vessel. This process requires a substance called plasmin or fibrinolysin.

Formation of Plasmin

Plasmin is formed from inactivated glycoprotein called plasminogen. Plasminogen is synthesized in liver

and it is incorporated with other proteins in the blood clot. Plasminogen is converted into plasmin by tissue plasminogen activator (t-PA), lysosomal enzymes and thrombin. The t-PA and lysosomal enzymes are released from damaged tissues and damaged endothelium. Thrombin is derived from blood. The t-PA is always inhibited by a substance called t-PA inhibitor. It is also inhibited by factors V and VIII.

Besides t-PA, there is another plasminogen activator called urokinase plasminogen activator (u-PA). It is

derived from blood.

Sequence of Events Involved in the Activation of Plasminogen

1. During intravascular clotting, the endothelium of the blood vessel secretes a thrombin-binding protein, the thrombomodulin. It is secreted by the endothelium of all the blood vessels, except the minute vessels

of brain

2. Thrombomodulin combines with thrombin and forms a thrombomodulin-thrombin complex

3. Thrombomodulin-thrombin complex activates protein C

4. Activated protein C inactivates factor V and VIII in the presence of a cofactor called protein S

5. Protein C also inactivates the t-PA inhibitor

6. Now, the t-PA becomes active

7. Activated t-PA and lysosomal enzymes activate plasminogen to form plasmin. Plasminogen is also

activated by thrombin and u-PA


Under physiological conditions, intravascular clotting does not occur. It is because of the presence of some physicochemical factors in the body.

1. Physical Factors

i. Continuous circulation of blood.

ii. Smooth endothelial lining of the blood vessels.

2. Chemical Factors – Natural Anticoagulants

i. Presence of natural anticoagulant called heparin that is produced by the liver

ii. Production of thrombomodulin by endothelium of the blood vessels (except in brain capillaries).

Thrombomodulin is a thrombin-binding pro tein. It binds with thrombin and forms a thrombomodulin-

thrombin complex. This complex activates protein C. Activated protein C along with its cofactor protein S inactivates Factor V and Factor VIII. Inactivation of these two clotting factors prevents clot formation

iii. All the clotting factors are in inactive state.


Substances which prevent or postpone coagulation of blood are called anticoagulants.

Anticoagulants are of three types:

1. Anticoagulants used to prevent blood clotting inside the body, i.e. in vivo.

2. Anticoagulants used to prevent clotting of blood that is collected from the body, i.e. in vitro.

3. Anticoagulants used to prevent blood clotting both in vivo and in vitro.


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