GOAGULATION

1. COAGULATION FACTORS
1
Presented by : Dr.
Vishal kr.
Kandhway

2. Definition
2
 Coagulation or clotting 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.

3. 3
 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

4. Factor Synonyms Half life
(hrs)
Deficiency
syndromes
Cause
I Fibrinogen 100-150 Afibrinogenemia Premature sep of
placenta/congenital
II Prothrombin 50-80 Hypo-
prothrombinemia
Decreased Hepatic
synthesis /secondary to
Vit K Def
III Tissue factor/
Thromboplastin
IV Calcium Ion
V Proaccelerin/
Labile Factor
24 Para hemophillia Congenital
COAGULATON NOMENCLATURE :

5. Factor Synonyms Half
life(hr)
Deficiency
syndromes
Cause
VII S.Prothrombin
converter accelerator
Stable factor
6 Hypoconvertinemia Congenital
VIII Antihemophillic factor
AHF-A,VIII:C
12 Hemophillia –A
Classical Hemophillia
Congenital :
X linked
IX Christmas Factor
AHF-B
24 Hemophillia –B
Christmas disease
Congenital
X Stuart prower factor
Auto prothrombin
25-60 Stuart prower factor
def
Congenital
XI Plasma thromboplastin
antecedent
AHF-C
40-80 PTA def Congenital
XII Hageman /contact 50-70 Hageman trait Congenital
XIII Fibrin stabilising 150

6. Sequence of clotting mechanism
6
 Enzyme Cascade theory :
 Most of the clotting factors are proteins in the form of
enzymes.
 Normally all the factors are present in the form of
inactive proenzyme.
 These proenzymes must be activated into enzymes to
enforce clot formation.
 It is carried out by a series of proenzyme-enzyme
conversion reactions.
 First one of the series is converted into an active
enzyme that activates the 2nd one, which activates the
3rd one, this is continued till final active enzyme
thrombin is formed.
 Cascade refers to a process that occurs through a
series of steps, each step initializing the next, until the

7. 7
 Stages of Blood clotting :
1) Formation of prothrombin activator
2) Conversion of prothrombin into thrombin
3) Conversion of fibrinogen into fibrin.

8. 8
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

9. 9
 Intrinsic pathway for the formation of Prothrombin
activator :
In this pathway the formation of prothrombin activator is
initiated by platelets, which are within the blood itself.
 Sequence of events :
1) During the injury, blood vessel is ruptured. Endothelium
is damaged & collagen beneath the endothelium is
exposed.
2) When factor XII comes in contact with collagen, it is
converted into activated factor XII in the presence of
kallikrein & high molecular weight (HMW) kinogen.
3) Activated factor XII converts factor XI into activated
factor XI in the presence of HMW kinogen.
4) The activated factor XI activates factor IX in the
presence of factor IV(calcium)
5) Activated factor IX activated factor X in the presence of
factor VIII & calcium.

10. 10
6) When platelets comes in contact with collagen of
damaged blood vessel, it gets activated & releases
phospholipids.
7) Now the activated factor X reacts with platelet
phospholipid & factor V to form prothrombin activator.
This needs the presence of calcium ions.
8 ) Factor V is also activated by positive feedback effect
of thrombin.

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• Extrinsic pathway for the formation of Prothrombin
activator :
In this pathway, the formation of prothrombin activator is
initiated by the tissue thromboplastin, which is formed
from the injured tissues.
• Sequence of events :
1) Tissues that are damaged during injury release tissue
thromboplastin(factor III). Thromboplastin contain
proteins, phospholipid & glycoprotein, which act as
proteolytic enzymes.
2) Glycoprotein & phospholipid components of
thromboplastin convert factor X into activated factor X
in the presence of factor VII.
3) Activated factor X reacts with factor V and
phospholipid component of tissue thromboplastin to

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2) Stage 2 : Conversion of prothrombin into thrombin
Blood clotting is all about thrombin formation. Once
thrombin is formed, it definetly leads to clot formation.
• Sequence of events in stage 2 :
1) Prothrombin activator that is formed in intrinsic &
extrinsic pathways, converts prothrombin into thrombin
in the presence of calcium(factor IV).
2) Once formed thrombin initiates the formation of more
thrombin molecules. The initially formed thrombin
activates factor V. Factor V in turn accelerates formation
of both extrinsic & intrinsic prothrombin activator, which
converts prothrombin in thrombin. This effect of
thrombin is called positive feedback effect.

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 Stage 3 : Conversion of fibrinogen into fibrin
The final stage of blood clotting involves the conversion of
fibrinogen into fibrin by thrombin.
 Sequence of events in stage 3 :
1) 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.
2) Fibrin monomer polymerizes with other monomer
molecules & form loosly arranged strands of fibrin.
3) Later these loose strands are modified into dense &
tight fibrin threads by fibrin stabilizing factor(factor XIII)
in the presence of calcium ions. All the tight fibrin
threads are aggregated to form a meshwork of stable
clot.

14. 14

15. 15
 Blood Clot : defined as the mass of coagulated blood
which contains RBC, WBC & platelets entrapped in fibrin
meshwork.
 RBC & WBC are not necessary for clotting process.
However whn clot is formed, these cells are trapped in it
along with platelets. The trapped RBC’S are responsible
for the red colour of the clot.
 The external blood clot is called scab. It adheres to the
opening of damaged blood vessel & prevents blood loss.

16. 16
 Clot Retraction : After the formation, the blood clot
starts contracting. And after about 30-45 mins, the straw
coloured serum oozes out of the clot. The process
involving the contraction of blood clot & oozing of the
serum is called clot retraction.
 Contractile proteins actin, myocin & thrombostenin are
responsible for clot retraction.

17. 17
 Fibrinolysis :
 Lysis of blood clot inside the blood vessel is called
fibrinolysis.
 It helps to remove the clot from lumen of the blood
vessel by the help of plasmin fibrinolysin.

18. 18

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 Fibrinogen (factor I) :
 Glycoprotein that helps in the formation of blood clots.
 Fibrinogen molecule is a soluble large & complex
glycoprotein that is converted by thrombin into fibrin
during blood clot formation.
 It is synthesized in the liver by hepatocytes.
Concentration of fibrinogen in the blood plasmais 200-
400 mg/dl.
 Deficiency can lead to either bleeding or thrombo-
embolic complication.
 Aquired deficiency is found after hemodilution, blood loss
in trauma patients & also in sepsis.
 In patients with fibrinogen deficiency, the correction of
bleeding is possible by infusion of FFP, cryoprecipitate or
by fibrinogen concentrates.

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 Prothrombin :
 is produced in the liver & is co-translationally modified
in a vit K dependant reaction that converts 10 glutamic
acid on prothrombin to gamma carboxy-glutamic acid.
 In the presence of calcium, the gamma carboxy-glutamic
acid residues promote the binding of prothrombin to
phospholipid bilayers.
 Deficiency of vit K or administration of the anti-coagulant
(warfarin) inhibits the production of gamma carboxy-
glutamic acid residues, slowing the activation of the
coagulation cascade.
 Thrombin is produced by the enzymatic cleavage of two
sites of prothrombin by activated factor X.
 The activity of factor X is greatly enhanced by binding to
activated factor V, termed the prothrombinase complex.

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 Thromboplastin (factor III) :
 It is a plasma protein aiding blood coagulation through
catalyzing the conversion of prothrombin to thrombin.
 It is a complex enzyme that is founf in brain, lung &
especially in the blood platelets & that function in the
conversion of prothrombin to thrombin in the clotting of
blood- called also thrombokinase.
 Thromboplastin is the combination of both phospholipids
& tissue factor, both needed in the activation of extrinsic
pathway.

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 Bleeding Disorders : Condition characterized by
prolong bleeding/clotting time.
 3 types : 1) Hemophilia
2) Purpura
3) von Willebrand disease
1) Hemophilia : group of sex-linked inherited disorder
characterized by prolong clotting time. However the
bleeding time is normal.
 Affects the males with carrier females.
 Because of prolonged clotting time even a mild trauma
causes excess bleeding which can lead to death.
 Easy brusing or hemorrhage in muscles & joints are
common.

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 Causes : occurs due to lack of formation of prothrombin
activator & hence the coagulation time is prolonged.
 Formation of prothrombin activator is affected due to the
deficiency of factor VIII, IX or XI.
 3 Types :
1) Hemophilia A or classic hemophilia : due to the
deficiency of factor VIII.
2) Hemophilia B or Christmas disease : due to the
defeciency of factor IX.
3) Hemophilia C : due to the deficiency of factor XI.

24. 24
 Symptoms include :
a) Spontaneous bleeding
b) Prolonged bleeding due to cuts, tooth extraction &
surgery.
c) Hemorrhage in GI & Urinary tracts.
d) Bleeding in joints followed by swelling & pain.
e) Appearance of blood in urine.
Treatment include replacement of missing clotting factor.

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2) Purpura : disorder characterized by prolong bleeding
time. However the clotting time is normal.
 Characteristic feature of this disease is spontaneous
bleeding under the skin from ruptured capillaries.
 It causes small tiny hemorrhagic spots in many areas of
the body (purple coloured patch like appearence)
 Blood also sometimes collect in large areas beneath the
skin called ecchymosea.

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 Types & causes :
1. Thrombocytopenic purpura :due to deficiency of
platelets(thrombocytopenia). In bone marrow disease
platelet production is affected leading to deficiency of
platelets.
2. Idiopathic thrombocytopenic purpura : It is believed
that platelet count decreases due to development of
antibodies against platelets which occurs after blood
transfusion.
3. Thrombasthenic purpura : due to structural or
functional abnormality of platelets. However platelet
count is normal

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 Von-willebrand disease : is a bleeding disorder
characterized by excessive bleeding even with a mild
injury.
 It is due to deficiency of von-willebrand factor, which is a
protein secreted by endothelium of damaged blood
vessels & platelets.
 This protein is responsible for adherence of platelets to
endothelium of blood vessels during hemostasis after an
injury.
 It is also responsible for the survival & maintainance of
factor VIII in plasma.
 It also causes deficiency of factor VIII

28. 28
 Tests for Blood clotting :
i. Bleeding time
ii. Clotting time
iii. Prothrombin time
iv. Partial prothrombin time
v. International normalized ratio
vi. Thrombin time

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