Blood clotting is a process called coagulation where blood loses fluidity and forms a mesh of fibrin fibrils entangling blood cells. There are 12 coagulation factors involved in a sequential process to convert fibrinogen into fibrin. First, the extrinsic and intrinsic pathways form prothrombin activator which converts prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin to form the clot. Anticoagulants like heparin and warfarin prevent clotting by interfering with parts of this coagulation cascade.

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

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

3.  Factor I : Fibrinogen
 Factor II : Prothrombin
 Factor III: Thromboplastin
 Factor IV: Calcium
 Factor V: Labile factor(Proaccelerin or
accelerator globulin)
 Factor VII: Stable factor
 Factor VIII: Antihemophilic factor
 Factor IX: Christmas factor
 Factor X: Stuart – Prower factor
 Factor XI: Plasma thromboplastin antecedent
 Factor XII: Hegman factor
 Factor XIII: Fibrin stabilizing factor
“FPT CLS
ACS PHF”

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

5. 1) Formation of prothrombin activator.
2) Conversion of prothrombin into thrombin.
3) Conversion of fibrinogen into fibrin.
During the process of blood clotting, the clotting
factors, which are in inactive forms, are
converted into active forms.

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

7. EXTRINSIC PATHWAY
Tissue trauma
Tissue thromboplastin
(Protein, Glycoprotein, Phospholipid)
↓
Factor X
Calcium→
→ Activated Factor X
↓ ← Factor V←Thrombin
Prothrombin Activator

8. INTRINSIC PATHWAY
Blood trauma
↓
Endothelial cells expose collagen
fibres
Factor XII → Activated Factor XII
With Calcium Activates Factor X

9. Factor X → Activated Factor X
Calcium → ↓
← Factor V← Thrombin
↓
Prothrombin Activator

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

11. Stage 3 : Conversion of
Fibrinogen into Fibrin
During this, the soluble Fibrinogen is converted
into insoluble Fibrin by Thrombin. Initially, the
fibrinogen is converted into activated fibrinogen,
which is called fibrin monomer. This polymerizes
with other monomer molecules to form Fibrin.
The first formed fibrin contains loosely arranged
strands. This is modified later into a dense tight
aggregate by fibrin stabilizing factor (Factor XII)
& this reaction requires the presence of calcium
ions.

12. FIBRINOGEN
Thrombin → ↓
ACTIVATED FIBRINOGEN
↓ polymerization
FIBRIN – loose strands
Factor XIII→ ↓ ←Calcium
FIBRIN – tight clot

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

14. The various
anticoagulants are as
follows:






Heparin
Dicoumoral
Warfarin
EDTA(ethylenediaminetetraacetic acid)
Oxalate compounds
Citrates(sodium, ammonium or potassium
citrate)

15. Tests for Clotting:
1. Bleeding Time- (2-8 Minutes)
2. Clotting Time (5-15 Minutes) by Capillary
tube method.
3. Prothrombin Time- (11-13 Seconds)