BLOOD CLOTTING - Edited

BIOCHEMICAL PHYSIOLOGY
By- Kshitij Bhavsar
Blood Coagulation
Blood coagulation or clotting is an important phenomenon to

prevent excess loss of blood in case of injury or trauma
a. The blood stops owing from a wound in case of injury. The blood
clot or ‘coagulum’ is formed by a network of brin threads. In this
network, deformed and dead formed elements (erythrocytes,
leukocytes and platelets) get trapped.
Prothrombin is the inactive form of thrombin that is present in the

plasma. Thrombokinase converts prothrombin to active thrombin
which in turn activates brinogen to brin. All these clotting factors
help in blood coagulation.
An injury stimulates platelets or thrombocytes to release various

factors that initiate the blood clotting cascade. Calcium ions play an
important role in blood coagulation.
Let’s learn more in detail about the process of blood coagulation

(clotting).
Factors Involved in Blood Coagulation

First let’s glance at the coagulation factors involved in the blood
clotting process.
Coagulation of blood occurs through a series of reactions due to the

activation of a group of substances called clotting factors. There are
13 clotting factors identi ed and named after the scientists who
discovered them or as per the activity. Only factor IX or Christmas
factor is named after the patient in whom it was discovered.
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Factor VI Factor XI Plasma
Factor I Fibrinogen
Unassigned thromboplastin antecedent
Factor II Prothrombin Factor VII Stable Factor XII Hageman factor

factor
Factor III Factor VIII Factor XIII Fibrin-stabilising
Thromboplastin Antihemophilic factor
Factor IV Calcium Factor IX Christmas
Factor factor
Factor V Labile factor Factor X Stuart-
(Proaccelerin) Prower factor
Blood Coagulation Pathway

The process of blood coagulation leads to haemostasis, i.e.
prevention of bleeding or haemorrhage. Blood clotting involves
activation and aggregation of platelets at the exposed endothelial
cells, followed by deposition and stabilisation of cross-linked brin
mesh.
Primary haemostasis involves platelet aggregation and formation of

a plug at the site of injury, and secondary haemostasis involves
strengthening and stabilisation of platelet plug by the formation of a
network of brin threads. The secondary haemostasis involves two
coagulation pathways, the intrinsic pathway and the extrinsic
pathway. Both pathways merge at a point and lead to the activation
of brin, and the formation of the brin network.
Platelet Activation
The blood circulating in the blood vessel does not clot under normal
circumstances. The blood coagulation process is stimulated when
there is any damage to the endothelium of blood vessels. It leads to
platelet activation and aggregation. When collagen is exposed to
the platelets due to injury, the platelets bind to collagen by surface
receptors. This adhesion is stimulated by the von Willebrand factor
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released from endothelial cells and platelets. This forms additional
cross-linking and activation of platelet integrins, which facilitate tight
binding and aggregation of platelets at the site of injury. This leads
to primary haemostasis.
Blood Coagulation Cascade

The process of coagulation is a cascade of enzyme catalysed
reactions wherein the activation of one factor leads to the activation
of another factor and so on.
The three main steps of the blood coagulation cascade are as

follows:
1. Formation of prothrombin activator

2. Conversion of prothrombin to thrombin
3. Conversion of brinogen into brin
1. Formation of prothrombin activator
The formation of a prothrombin activator is the rst step in the blood

coagulation cascade of secondary haemostasis. It is done by two
pathways, viz. extrinsic pathway and intrinsic pathway.
Extrinsic Coagulation Pathway
It is also known as the tissue factor pathway. It is a shorter pathway.

The tissue factors or tissue thromboplastins are released from the
damaged vascular wall. The tissue factor activates the factor VII to
VIIa. Then the factor VIIa activates the factor X to Xa in the
presence of Ca2+.
Intrinsic Coagulation Pathway
It is the longer pathway of secondary haemostasis. The intrinsic

pathway begins with the exposure of blood to the collagen from the
underlying damaged endothelium. This activates the plasma factor
XII to XIIa.
XIIa is a serine protease, it activates the factor XI to XIa. The XIa

then activates the factor IX to IXa in the presence of Ca2+ ions.
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The factor IXa in the presence of factor VIIIa, Ca2+ and
phospholipids activate the factor X to Xa.
Common Pathway
The factor Xa, factor V, phospholipids and calcium ions form the
prothrombin activator. This is the start of the common pathway of
both extrinsic and intrinsic pathways leading to coagulation.
2. Conversion of prothrombin to thrombin
Prothrombin or factor II is a plasma protein and is the inactive form

of the enzyme thrombin. Vitamin K is required for the synthesis of
prothrombin in the liver. The prothrombin activator formed above
converts prothrombin to thrombin. Thrombin is a proteolytic
enzyme. It also stimulates its own formation, i.e. the conversion of
prothrombin to thrombin. It promotes the formation of a prothrombin
activator by activating factors VIII, V and XIII.
3. Conversion of brinogen into brin
Fibrinogen or factor I is converted to brin by thrombin. Thrombin

forms brin monomers that polymerise to form long brin threads.
These are stabilised by the factor XIII or brin stabilising factor. The
brin stabilising factor is activated by thrombin to form factor XIIIa.
The activated brin stabilising factor (XIIIa) forms cross-linking
between brin threads in the presence of Ca2+ and stabilises the
brin meshwork. The brin mesh traps the formed elements to form
a solid mass called a clot.
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Blood Clotting Disorders
Haemophilia is the main blood clotting disorder. Haemophilia is
characterised by excessive bleeding. It is due to the absence of
some of the factors required in the blood clotting cascade. The
three main forms of haemophilia are as follows:
• Haemophilia A – Factor VIII de ciency

• Haemophilia B – Factor IX de ciency or “Christmas disease”
• Haemophilia C – Factor XI de ciency
Thrombosis is the formation of a blood clot inside the blood vessel.
It blocks the ow of blood. Thrombosis can occur in arteries as well
as veins. Arterial thrombosis affects the blood supply and leads to
the damage of tissue, i.e. ischemia or necrosis. The clot may
sometimes break free and circulate in the body and lead to
embolism.
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BIOCHEMICAL PHYSIOLOGY

By- Kshitij Bhavsar

Blood coagulation or clotting is an important phenomenon to

Prothrombin is the inactive form of thrombin that is present in the

An injury stimulates platelets or thrombocytes to release various

Let’s learn more in detail about the process of blood coagulation

Factors Involved in Blood Coagulation

Coagulation of blood occurs through a series of reactions due to the

Factor II Prothrombin Factor VII Stable Factor XII Hageman factor

Blood Coagulation Pathway

Primary haemostasis involves platelet aggregation and formation of

Blood Coagulation Cascade

The three main steps of the blood coagulation cascade are as

1. Formation of prothrombin activator

The formation of a prothrombin activator is the rst step in the blood

Extrinsic Coagulation Pathway

It is also known as the tissue factor pathway. It is a shorter pathway.

Intrinsic Coagulation Pathway

It is the longer pathway of secondary haemostasis. The intrinsic

XIIa is a serine protease, it activates the factor XI to XIa. The XIa

2. Conversion of prothrombin to thrombin

Prothrombin or factor II is a plasma protein and is the inactive form

3. Conversion of brinogen into brin

Fibrinogen or factor I is converted to brin by thrombin. Thrombin

• Haemophilia A – Factor VIII de ciency

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