CONTENTS
BLOOD COAGULATION
FACTORS INVOLVED IN BLOOD
COAGULATION
BLOOD COAGULATION PATHWAY
BLOOD CLOOTING DISORDERS
BlOOd COagulaTiON
Blood coagulation or clotting is an important
phenomenon to prevent excess loss of blood
in case of injury or trauma. The blood stops
flowing from a wound in case of injury. The
blood clot or ‘coagulum’ is formed by a
network of fibrin 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 fibrinogen to fibrin. 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.
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 identified 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.
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
fibrin 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 fibrin 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
fibrin, and the formation of the fibrin 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 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 fibrinogen into fibrin
1. FOrMaTiON OF prOThrOMBiN
The formation of a prothrombin activator is the
first 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.
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.
[Link] OF FriBriNOgEN
iNTO FiBriN
Fibrinogen or factor I is converted to fibrin by
thrombin. Thrombin forms fibrin monomers
that polymerise to form long fibrin threads.
These are stabilised by the factor XIII or fibrin
stabilising factor. The fibrin stabilising factor is
activated by thrombin to form factor XIIIa. The
activated fibrin stabilising factor (XIIIa) forms
cross-linking between fibrin threads in the
presence of Ca2+ and stabilises the fibrin
meshwork. The fibrin mesh traps the formed
elements to form a solid mass called a clot.
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 deficiency
Haemophilia B – Factor IX deficiency or
“Christmas disease”
Haemophilia C – Factor XI deficiency
Thrombosis is the formation of a blood clot
inside the blood vessel. It blocks the flow 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.
FrEquENTly aSkEd quESTiONS
Q1. Define blood coagulation
Ans. Coagulation or clotting is defined as the
process in which blood loses its fluidity and
becomes a jelly-like mass a few minutes after
it is shed out. It is a vital phenomenon to
prevent excess loss of blood in case of injury
or trauma.
Q2. What is a blood clot?
Ans. Coagulation or clotting is defined as the
process in which blood loses its fluidity and
becomes a jelly-like mass a few minutes after
it is shed out. It is a vital phenomenon to
prevent excess loss of blood in case of injury
or trauma.
Q3. What is fibrinolysis?
Ans. Lysis of blood clot inside the blood
vessel is called fibrinolysis. It aids in the
removal of clots from lumen of the blood
vessel. This process happens in the presence
of a substance called fibrinolysin or plasmin.
Q4. What are anticoagulants?
Ans. Substances which prevent or postpone
coagulation of blood are called
anticoagulants. Examples – EDTA and
heparin. Sodium, potassium and ammonium
citrates are also used as anticoagulants.
BiBliOgraphy
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