Blood clotting

1. BLOOD CLOTTINGBLOOD CLOTTING
When blood is shed out or collected in a When blood is shed out or collected in a
container, it looses its fluidity & becomes a container, it looses its fluidity & becomes a
jelly like mass after few minutes. This process jelly like mass after few minutes. This process
is called coagulation or clotting of blood. The is called coagulation or clotting of blood. The
clot is a mesh of thin fibrils entangling the clot is a mesh of thin fibrils entangling the
blood cells. These fibrils consist of fibrin. The blood cells. These fibrils consist of fibrin. The
fibrin is formed from fibrinogen. fibrin is formed from fibrinogen.

2. FACTORS INVOLVED IN FACTORS INVOLVED IN
BLOOD CLOTTINGBLOOD CLOTTING

Coagulation of blood occurs through a Coagulation of blood occurs through a
series of reactions due to the activation of series of reactions due to the activation of
a variety of substances. Those a variety of substances. Those
substances necessary for clotting are substances necessary for clotting are
called clotting factors. The clotting factors called clotting factors. The clotting factors
are : are :

3. Factor I : FibrinogenFactor I : Fibrinogen
Factor II : ProthrombinFactor II : Prothrombin
Factor III: ThromboplastinFactor III: Thromboplastin
Factor IV: CalciumFactor IV: Calcium
Factor V: Labile factor(Proaccelerin or Factor V: Labile factor(Proaccelerin or
accelerator globulin)accelerator globulin)
Factor VII: Stable factor Factor VII: Stable factor
Factor VIII: Antihemophilic factorFactor VIII: Antihemophilic factor
Factor IX: Christmas factorFactor IX: Christmas factor
Factor X: Stuart – Prower factorFactor X: Stuart – Prower factor
Factor XI: Plasma thromboplastin antecedentFactor XI: Plasma thromboplastin antecedent
Factor XII: Hegman factorFactor XII: Hegman factor
Factor XIII: Fibrin stabilizing factor Factor XIII: Fibrin stabilizing factor

4. SEQUENCE OF SEQUENCE OF
CLOTTING MECHANISMCLOTTING MECHANISM
Normally during circulation, the blood Normally during circulation, the blood
does not clot, because the enzymes does not clot, because the enzymes
involved in clotting are in inactive form. involved in clotting are in inactive form.
Slight initial activation causes clotting in Slight initial activation causes clotting in
which each enzyme activates another one which each enzyme activates another one
in a sequential manner till the conversion in a sequential manner till the conversion
of fibrinogen into fibrin. In general, of fibrinogen into fibrin. In general,
clotting occurs in 3 stages namely:clotting occurs in 3 stages namely:

5. Formation of prothrombin activator.Formation of prothrombin activator.
Conversion of prothrombin into thrombin.Conversion of prothrombin into thrombin.
Conversion of fibrinogen into fibrin.Conversion of fibrinogen into fibrin.
During the process of blood clotting, the clotting During the process of blood clotting, the clotting
factors, which are in inactive forms, are factors, which are in inactive forms, are
converted into active forms. And their converted into active forms. And their
enzymatic actions produce the successive enzymatic actions produce the successive
reactions one after another in a cascading reactions one after another in a cascading
manner.manner.
Thus, the various reactions involved in blood Thus, the various reactions involved in blood
clotting are explained by Enzyme cascade clotting are explained by Enzyme cascade
theory. theory.

6. Stage 1 : Formation of Stage 1 : Formation of
prothrombin activatorprothrombin activator
Prothrombin activator is formed in two ways Prothrombin activator is formed in two ways
namely: namely:
Extrinsic pathway:Extrinsic pathway: In this, the formation of In this, the formation of
prothrombin activator is initiated by the prothrombin activator is initiated by the
tissue thromboplastin.tissue thromboplastin.
Intrinsic pathwayIntrinsic pathway: In this, the formation of : In this, the formation of
prothrombin activator is initiated by prothrombin activator is initiated by
platelets, which are within the blood itself.platelets, which are within the blood itself.

7. EXTRINSIC PATHWAYEXTRINSIC PATHWAY
Tissue traumaTissue trauma
↓ ↓
Tissue thromboplastinTissue thromboplastin
(Protein, Glycoprotein, Phospholipid)(Protein, Glycoprotein, Phospholipid)
Factor VII→ ↓Factor VII→ ↓
Factor X → Activated Factor XFactor X → Activated Factor X
Calcium→ ↓ ← Factor V←ThrombinCalcium→ ↓ ← Factor V←Thrombin

Prothrombin ActivatorProthrombin Activator

8. INTRINSIC PATHWAYINTRINSIC PATHWAY
Tissue traumaTissue trauma
↓↓
Factor XII → Activated Factor XIIFactor XII → Activated Factor XII
kininogen→ ↓ ←Prekallkreinkininogen→ ↓ ←Prekallkrein
Factor XI →Activated Factor XIFactor XI →Activated Factor XI
Calcium → ↓Calcium → ↓
Factor IX → Activated Factor IX Factor IX → Activated Factor IX
Calcium → ↓ ←Factor VIIICalcium → ↓ ←Factor VIII

9. Factor X → Activated Factor XFactor X → Activated Factor X

Calcium → ↓ ← Factor V← Thrombin Calcium → ↓ ← Factor V← Thrombin

↓ ↓
Prothrombin ActivatorProthrombin Activator

10. Stage 2 : Conversion of Stage 2 : Conversion of
prothrombin into prothrombin into
thrombinthrombin
Prothrombin activator converts Prothrombin Prothrombin activator converts Prothrombin
into Thrombin in the presence of Calcium. into Thrombin in the presence of Calcium.
Thrombin itself can accelerate this reaction Thrombin itself can accelerate this reaction
by positive feedback mechanism. That is, the by positive feedback mechanism. That is, the
initial Thrombin activates Factor V. This in initial Thrombin activates Factor V. This in
turn accelerates the formation of both turn accelerates the formation of both
Extrinsic & Intrinsic Prothrombin activator.Extrinsic & Intrinsic Prothrombin activator.

11. Stage 3 : Conversion of Stage 3 : Conversion of
Fibrinogen into FibrinFibrinogen into Fibrin

During this, the soluble Fibrinogen is converted During this, the soluble Fibrinogen is converted
into insoluble Fibrin by Thrombin. Initially, the into insoluble Fibrin by Thrombin. Initially, the
fibrinogen is converted into activated fibrinogen, fibrinogen is converted into activated fibrinogen,
which is called fibrin monomer. This polymerizes which is called fibrin monomer. This polymerizes
with other monomer molecules to form Fibrin.with other monomer molecules to form Fibrin.
The first formed fibrin contains loosely arranged The first formed fibrin contains loosely arranged
strands. This is modified later into a dense tight strands. This is modified later into a dense tight
aggregate by fibrin stabilizing factor (Factor XII) & aggregate by fibrin stabilizing factor (Factor XII) &
this reaction requires the presence of calcium this reaction requires the presence of calcium
ions. ions.

12. FIBRINOGENFIBRINOGEN
Thrombin → ↓Thrombin → ↓
ACTIVATED FIBRINOGENACTIVATED FIBRINOGEN
↓ ↓ polymerizationpolymerization
FIBRIN – loose strandsFIBRIN – loose strands
Factor XIII→ ↓ ←CalciumFactor XIII→ ↓ ←Calcium
FIBRIN – tight clotFIBRIN – tight clot

13. ANTICOAGULANTSANTICOAGULANTS
The substances, which prevent or postpone The substances, which prevent or postpone
coagulation of blood, are called coagulation of blood, are called
anticoagulants. Some substances are used anticoagulants. Some substances are used
to prevent clotting inside the body i.e., in to prevent clotting inside the body i.e., in
vivo & some substances used to prevent vivo & some substances used to prevent
clotting outside the body i.e., in vitro.clotting outside the body i.e., in vitro.

14. The various The various
anticoagulants are as anticoagulants are as
follows:follows:
HeparinHeparin
DicoumoralDicoumoral
WarfarinWarfarin
EDTA(ethylenediaminetetraacetic acid)EDTA(ethylenediaminetetraacetic acid)
Oxalate compoundsOxalate compounds
Citrates(sodium, ammonium or potassium Citrates(sodium, ammonium or potassium
citrate)citrate)

15. Anticoagulants are Anticoagulants are
used:used:
For the prophylaxis or treatment of For the prophylaxis or treatment of
thromboembolic disorders.thromboembolic disorders.
For preservation of stored whole blood & For preservation of stored whole blood &
blood fractions (heparin & acid citrate blood fractions (heparin & acid citrate
dextrose).dextrose).
To keep laboratory blood specimens from To keep laboratory blood specimens from
clotting (EDTA, citrate, oxalate & fluoride). clotting (EDTA, citrate, oxalate & fluoride).

16. Tests for Clotting:Tests for Clotting:
1.1.Bleeding TimeBleeding Time
2.2.Clotting TimeClotting Time
3.3.Prothrombin TimeProthrombin Time

18. MICROVASCULATUREMICROVASCULATURE
The blood vessels are closed circuits for The blood vessels are closed circuits for
the transport of blood from the left heart to the transport of blood from the left heart to
the metabolizing cells, & then back to the the metabolizing cells, & then back to the
right heart. The blood containing oxygen, right heart. The blood containing oxygen,
nutrients & metabolites is routed through nutrients & metabolites is routed through
ARTERIESARTERIES, , ARTERIOLESARTERIOLES, , CAPILLARIESCAPILLARIES, ,
VENULESVENULES & & VEINSVEINS. These blood vessels . These blood vessels
differ from each other in their structure & differ from each other in their structure &
function. function.

19. Blood flows from the heart to arteries, Blood flows from the heart to arteries,
which branch & narrow into arterioles. The which branch & narrow into arterioles. The
arterioles give rise to metarterioles, which arterioles give rise to metarterioles, which
give rise to capillaries. After the tissue has give rise to capillaries. After the tissue has
been perfused, capillaries drain into been perfused, capillaries drain into
venules , which are then widen more to venules , which are then widen more to
become veins, & which return blood to the become veins, & which return blood to the
heart. heart.
The microcirculation of each organ is The microcirculation of each organ is
specially organized to serve that organ’s specially organized to serve that organ’s
own special needs – i.e., transport of own special needs – i.e., transport of
nutrients to the tissues & removal of nutrients to the tissues & removal of
cellular excreta.cellular excreta.

20. The “capillary bed” is the network of The “capillary bed” is the network of
capillaries supplying an organ.capillaries supplying an organ.
The capillaries are extremely thin The capillaries are extremely thin
structures with walls of a single layer of structures with walls of a single layer of
highly permeable endothelial cells. Here highly permeable endothelial cells. Here
interchange of nutrients and cellular interchange of nutrients and cellular
excreta occurs between the tissues & the excreta occurs between the tissues & the
circulating blood.circulating blood.
The walls of the arteries, arterioles & The walls of the arteries, arterioles &
small venules contain relatively large small venules contain relatively large
amounts of smooth muscle. The openings amounts of smooth muscle. The openings
of the capillaries are guarded by muscular of the capillaries are guarded by muscular
precapillary sphincters. precapillary sphincters.