ANTICLOTTING MECHANISM IN THE BODY

ANTICLOTTING MECHANISM IN THE BODY

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.

ANTICOAGULANTS

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.

1. HEPARIN

Heparin is a naturally produced anticoagulant in the body. It is produced by mast cells which are the wandering cells present immediately outside the capillaries in many tissues or organs that contain more connective tissue. These cells are abundant in liver and lungs. Basophils also secrete heparin.

Heparin is a conjugated polysaccharide. Commercial heparin is prepared from the liver and other organs of animals. Commercial preparation is available in liquid form or dry form as sodium, calcium, ammonium or lithium salts.

Mechanism of Action of Heparin

Heparin:

i. Prevents blood clotting by its antithrombin activity. It directly suppresses the activity of

thrombin

ii. Combines with antithrombin III (a protease inhibitor present in circulation) and removes

thrombin from circulation

iii. Activates antithrombin III

iv. Inactivates the active form of other clotting factors like IX, X, XI and XII.

Uses of Heparin

Heparin is used as an anticoagulant both in vivo and in vitro.

Clinical use

Intravenous injection of heparin (0.5 to 1 mg/kg body weight) postpones clotting for 3 to 4 hours (until it is

destroyed by the enzyme heparinase). So, it is widely used as an anticoagulant in clinical practice. In clinics, heparin is used for many purposes such as:

i. To prevent intravascular blood clotting during surgery.

ii. While passing the blood through artificial kidney for dialysis.

iii. During cardiac surgery, which involves heartlung machine.

iv. To preserve the blood before transfusion.

Use in the laboratory

Heparin is also used as anticoagulant in vitro while collecting blood for various investigations. About 0.1 to 0.2 mg is sufficient for 1 mL of blood. It is effective for 8 to 12 hours. After that, blood will clot because heparin only delays clotting and does not prevent it. Heparin is the most expensive anticoagulant.

2. COUMARIN DERIVATIVES

Warfarin and dicoumoral are the derivatives of coumarin.

Mechanism of Action

Coumarin derivatives prevent blood clotting by inhibiting the action of vitamin K. Vitamin K is essential for the formation of various clotting factors, namely II, VII, IX and X.

 Uses

Dicoumoral and warfarin are the commonly used oral anticoagulants ( in vivo). Warfarin is used to prevent myocardial infarction (heart attack), strokes and thrombosis.

3. EDTA

Ethylenediaminetetraacetic acid (EDTA) is a strong anticoagulant. It is available in two forms:

i. Disodium salt (Na2 EDTA).

ii. Tripotassium salt (K3 EDTA).

Mechanism of Action

These substances prevent blood clotting by removing calcium from blood.

Uses

EDTA is used as an anticoagulant both in vivo and in vitro. It is:

i. Commonly administered intravenously, in cases of lead poisoning.

ii. Used as an anticoagulant in the laboratory (in vitro). 0.5 to 2.0 mg of EDTA per mL of blood

is sufficient to preserve the blood for at least 6 hours. On refrigeration, it can preserve the blood

up to 24 hours.

4. OXALATE COMPOUNDS

Oxalate compounds prevent coagulation by forming calcium oxalate, which is precipitated later. Thus, these compounds reduce the blood calcium level. Earlier sodium and potassium oxalates were

used. Nowadays, mixture of ammonium oxalate and potassium oxalate in the ratio of 3 : 2 is used. Each

salt is an anticoagulant by itself. But potassium oxalate alone causes shrinkage of RBCs. Ammonium oxalate alone causes swelling of RBCs. But together, these substances do not alter the cellular activity.

Mechanism of Action

Oxalate combines with calcium and forms insoluble calcium oxalate. Thus, oxalate removes calcium from

blood and lack of calcium prevents coagulation.

Uses

Oxalate compounds are used only as in vitro anticoagulants. 2 mg of mixture is necessary for 1 ml

of blood. Since oxalate is poisonous, it cannot be used in vivo.

5. CITRATES

Sodium, ammonium and potassium citrates are used as anticoagulants.

Mechanism of Action

Citrate combines with calcium in blood to form insoluble calcium citrate. Like oxalate, citrate also removes calcium from blood and lack of calcium prevents coagulation.

Uses

Citrate is used as in vitro anticoagulant.

i. It is used to store blood in the blood bank as: a. Acid citrate dextrose (ACD): 1 part of ACD

with 4 parts of blood

b. Citrate phosphate dextrose (CPD): 1 part of CPD with 4 parts of blood

ii. Citrate is also used in laboratory in the form of formol-citrate solution (Dacie’s solution) for RBC

and platelet counts.

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