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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