BLOOD CLOT AND COMPOSITION OF CLOT
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.
CLOT RETRACTION
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.
FIBRINOLYSIS
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
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.
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