COAGULATION OF

BLOOD
 Hemostasis = arrest or stoppage of
blood
Stages:
* vasoconstriction
* platelet plug formation
* Coagulation of blood
Coagulation is defined as the process
in which blood loses its fluidity and becomes
a jelly-like mass few minutes after it is shed
out or collected in a container.
Factors involved in blood clotting :
Coagulation of blood occurs through a
series of reactions due to the activation of
group of substances. Substances necessary
for clotting are called clotting factors.
Thirteen clotting factors are identified:
Factor I - Fibrinogen
Factor II - Prothrombin
Factor III - Thromboplastin (Tissue factor)
Factor IV - Calcium
Factor V - Labile factor
Factor VI - Presence has not been proved
Factor VII - Stable factor
Factor VIII - Antihemophilic factor
Factor IX - Christmas factor
Factor X - Stuart-Prower factor
Factor XI - Plasma thromboplastin
antecedent
 Factor XII - Hageman factor
Factor XIII - Fibrin-stabilizing factor

Deficiency syndromes Cause:

I Fibrinogen - Afibrinogenemia Premature sep
of placenta/congenital
II Prothrombin - Hypo- prothrombinemia
Decreased Hepatic synthesis /secondary to Vit
K Def
III Tissue factor/ Thromboplastin
IV Calcium Ion
V Proaccelerin/ Labile Factor - Para
hemophillia Congenital
VII S.Prothrombin converter accelerator
Hypoconvertinemia Congenital
VIII Antihemophillic factor AHF-A,
Hemophillia –A Classical Hemophillia
Congenital : X linked
IX Christmas Factor AHF-B 24 Hemophillia –B
Christmas disease Congenital
X Stuart prower factor Auto prothrombin, def
Congenital
XI Plasma thromboplastin antecedent AHF-C
PTA def Congenital
XII Hageman /contact Hageman trait
Congenital
XIII Fibrin stabilizing, Fibrinase
Stages of Blood Clotting:
blood clotting occurs in three stages:
1. Formation of prothrombin activator
2. Conversion of prothrombin into thrombin
3. Conversion of fibrinogen into fibrin.
STAGE 1: FORMATION OF
PROTHROMBIN ACTIVATOR
Blood clotting commences with the
formation of a substance called
prothrombin activator, which converts
prothrombin into thrombin. Its formation
is initiated by substance produced either
within the blood or outside the blood. Thus
formation of prothrombin activator occurs
through 2 pathways :
a) Intrinsic pathway
b) Extrinsic pathway
Sequence of events in intrinsic pathway:
During the injury, blood vessel is
ruptured. Endothelium is damaged &
collagen beneath the endothelium is
exposed

When factor XII (Hageman factor) comes in

contact with collagen, it is converted
into activated factor XII

Activated factor XII converts factor XI

(Plasma thromboplastin) into activated factor
XI in the presence of HMW kinogen.
The activated factor XI activates factor IX (Christmas
Factor) in the presence of factor IV(calcium)

Activated factor IX activated factor X (Stuart prower

factor) in the presence of factor VIII ( Antihemophillic
factor) & calcium.

When platelets comes in contact with collagen of

damaged blood vessel, it gets activated & releases
phospholipids.

Now the activated factor X reacts with platelet

phospholipid & factor V (Labile Factor) to form
prothrombin activator. This needs the presence of
calcium ions
 Factor V (Labile Factor) is also activated by
positive feedback effect of thrombin.
Sequence of events in extrinsic
pathway:
The formation of prothrombin
activator is initiated by the tissue
thromboplastin, which is formed from
the injured tissues.
Tissues that are damaged during injury
release tissue thromboplastin(factor
III).
Thromboplastin contain proteins, phospholipid &
glycoprotein, which act as proteolytic enzymes.

Glycoprotein & phospholipid components of

thromboplastin convert factor X (Stuart prower
factor) into activated factor X in the presence of
factor VII (Prothrombin)

Activated factor X reacts with factor V (Labile

factor) and phospholipid component of tissue
thromboplastin to form prothrombin activator.
This reaction requires the presence of calcium
ions
 STAGE 2: CONVERSION OF
PROTHROMBIN INTO THROMBIN
Sequence of Events in Stage 2:
Prothrombin activator converts prothrombin
into thrombin in the presence of calcium (IV)

Once formed thrombin initiates the formation

of more thrombin molecules. The initially
formed thrombin activates factor V (Labile
factor), which converts prothrombin in
thrombin. This effect of thrombin is called
positive feedback effect.
STAGE 3: CONVERSION OF FIBRINOGEN
INTO FIBRIN
Sequence of Events in Stage 3:
Thrombin converts inactive fibrinogen
into activated fibrinogen due to loss of
2 pairs of polypeptides from each
fibrinogen molecule. The activated
fibrinogen is called fibrin monomer.

Fibrin monomer polymerizes with other

monomer molecules & form loosely
arranged strands of fibrin.
Later these loose strands are modified
into dense & tight fibrin threads by
factor XIII (fibrin stabilizing factor) in
the presence of calcium ions. All the
tight fibrin threads are aggregated to
form a meshwork of stable clot.
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.

FIBRINOLYSIS:
Lysis of blood clot inside the blood
vessel is called fibrinolysis. This process
requires a substance called plasmin or
fibrinolysin.
ANTICLOTTING MECHANISM IN THE BODY:
Physical Factors:
i. Continuous circulation of blood.
ii. Smooth endothelial lining of the blood vessels.
Chemical Factors:
i. Presence of natural anticoagulant called
heparin that is produced by the liver
ii. Production of thrombomodulin by endothelium
of the blood vessels.
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 (in vivo)
2. Anticoagulants used to prevent clotting of
blood that is collected from the body (in
vitro)
3. Anticoagulants used to prevent blood
clotting both in vivo and in vitro.
HEPARIN:
its produced by mast cells in liver and lungs.
Uses:
* Heparin is used as an anticoagulant both in vivo
and in vitro.
COUMARIN DERIVATIVES:
Warfarin and dicoumoral are the derivatives of
coumarin
EDTA:
It is available in two forms:
i. Disodium salt (Na2 EDTA).
ii. Tripotassium salt (K3 EDTA)
OXALATE COMPOUNDS:
only used in invitro
CITRATES
other substances which prevent blood clotting:
Peptone,
C-type lectin (proteins from venom of
viper)
hirudin (from the leach Hirudinaria
manillensis)
TESTS FOR BLOOD CLOTTING:
Bleeding time: it’s the time interval from oozing
of blood after a injury till arrest of bleeding.
Clotting time: it’s the time interval from oozing
of blood after a injury till clot formation.
Prothrombin time: it’s the time taken for the
blood to clot after adding tissue thromboplastin.
Partial prothrombin time (PTT/APTT): it’s the
time taken for the blood to clot after adding
phospholipid along with calcium.
International normalized ratio: it’s the ratio of
patients prothrombin time when compared to
the average.
Thrombin time: it’s the time taken for the blood
to clot after adding thrombin to it.
APPLIED PHYSIOLOGY:
„* BLEEDING DISORDERS
- Hemophilia
- Purpura
- Von Willebrand disease.
Hemophilia: characterized by prolonged
clotting time.
Types
Hemophilia A – Defn of Factor VIII
Hemophilia B – Defn of Factor IX
Hemophilia C – Defn of Factor XI
Treatment:
replacement of missing factor.
 Purpura:
characterized by prolonged bleeding time.
spontaneous bleeding under the skin from
ruptured capillaries.
 The hemorrhagic spots under the skin are
called purpuric spots.
Blood also sometimes collects in large areas
beneath the skin which are called
ecchymoses.
Types and causes of purpura:
i. Thrombocytopenic purpura
ii. Idiopathic thrombocytopenic purpura
iii. Thrombasthenic purpura
VonWillebrand Disease:
It is due to deficiency of von Willebrand
factor, which is a protein secreted by
endothelium of damaged blood vessels and
platelets. This protein is responsible for
adherence of platelets to endothelium of
blood vessels.
Deficiency of Von Willebrand factor
suppresses platelet adhesion. It also causes
deficiency of factor VIII.
* THROMBOSIS
Causes of Thrombosis
- injury to blood vessels
- Roughened endothelial lining
- Sluggishness of blood flow
- Agglutination of RBCs
- Toxic thrombosis
- Congenital absence of protein C
Complications:
1. Thrombus
2. Embolism
3. Ischemia
4. Necrosis
HOMOEOPATHIC MANAGEMENT:
ACTEA RECE, ARNICA, BELL,
BOTHROBS, CALENDULA, CROTALUS,
ERIGERON, FERRUM MET, HAMAMELIS,
LACH, MILLEFOLIUM, MELILOTUS,
PHOSPHORUS, SABINA, SECAL COR,
THALASPI BURSA.