TOPIC:BLOOD

COURSE CODE: PIO 201

CLASS: 200L FAH
BY

DR. IYARE CORDILIA

Outline
Blood clotting mechanism
Platelet plug (refer to notes on platelets aggregation)
Clot retraction
Definition
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.
FACTORS INVOLVED IN BLOOD CLOTTING
Coagulation of blood occurs through a series of
reactions due to the activation of a group of
substances. Substances necessary for clotting are
called clotting factors
Factor I Fibrinogen
Factor II Prothrombin
Factor III Thromboplastin (Tissue factor)
Factor IV Calcium
Factor V Labile factor (Proaccelerin or accelerator
globulin)
Factor VI Presence has not been proven
Factor VII Stable factor
Factor VIII Antihemophilic factor (Antihemophilic
globulin)
Factor IX Christmas factor
Factor X Stuart-Prower factor
Factor XI Plasma thromboplastin antecedent(PTA)
Factor XII Hageman factor (Contact factor)
Factor XIII Fibrin-stabilizing factor (Fibrinase)

Clotting factors were named after the scientists who

discovered them or as per the activity, except factor IX.
Factor IX or Christmas factor was named after the
patient in whom it was discovered.
SEQUENCE OF CLOTTING MECHANISM

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 or 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 second one, which activates the third one; this
continues till the final active enzyme thrombin is formed.

Enzyme cascade theory explains how various reactions,

involved in the conversion of proenzymes to active enzymes
take place in the form of a cascade.

Cascade refers to a process that occurs through a series of

steps, each step initiating the next, until the final step is
reached.
Stages of Blood Clotting
In general, 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 substances produced either within the
blood or outside the blood. Thus, formation of
prothrombin activator occurs through two pathways:
i. Intrinsic pathway
ii. Extrinsic pathway
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 in Intrinsic pathway
 i. During the injury, the blood vessel is ruptured.
Endothelium is damaged and collagen beneath the
endothelium is exposed.
ii. When factor XII (Hageman factor) comes in contact with
collagen, it is converted into activated factor XII in the
presence of kallikrein and high molecular weight (HMW)
kinogen.
iii. The activated factor XII converts factor XI into activated
factor XI in the presence of HMW kinogen.
iv. The activated factor XI activates factor IX in the presence
of factor IV (calcium)
v. Activated factor IX activates factor X in the presence of
factor VIII and calcium.
vi. When platelet comes in contact with collagen of
damaged blood vessel, it gets activated and releases
phospholipids.
vii. Now the activated factor X reacts with platelet
phospholipid and factor V to form prothrombin activa tor.
This needs the presence of calcium ions.
 viii. Factor V is also activated by positive feedback effect
of thrombin
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 in Extrinsic Pathway
i. Tissues that are damaged during injury release tissue
thromboplastin (factor III).
 Thromboplastin contains proteins, phospholipid and
glycoprotein, which act as proteolytic enzymes.
 ii. Glycoprotein and phospholipid components of
thromboplastin convert factor X into activated factor
X, in the presence of factor VII.
iii. Activated factor X reacts with factor V 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
Blood clotting is all about thrombin formation. Once
thrombin is formed, it definitely leads to clot formation.
Sequence of Events in Stage 2
i. Prothrombin activator that is formed in intrinsic and
extrinsic pathways converts prothrombin into thrombin
in the presence of calcium (factor IV).
ii. 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
and intrinsic prothrombin activator, which converts
prothrombin into thrombin.
This effect of thrombin is called positive feedback effect
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
i. 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.
 ii. Fibrin monomer polymerizes with other monomer
molecules and form loosely arranged strands of fibrin.
iii. Later these loose strands are modified into dense
and 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.
BLOOD CLOT: „ DEFINITION AND
COMPOSITION OF CLOT

Blood clot is defined as the mass of coagulated blood
which contains RBCs, WBCs and platelets entrapped
in fibrin meshwork.
 RBCs and WBCs are not necessary for clotting
process.
However, when clot is formed, these cells are trapped
in it along with platelets.
 The trapped RBCs are responsible for the red color of
the clot.
 The external blood clot is also called scab.
It adheres to the opening of damaged blood vessel and
prevents blood loss
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.
Contractile proteins, namely actin, myosin and
thrombosthenin in the cytoplasm of platelets are
responsible for clot retraction

FIBRINOLYSIS Lysis of blood clot inside the blood vessel

is called fibrinolysis.
It helps to remove the clot from lumen of the blood vessel.
This process requires a substance called plasmin or
fibrinolysin
Formation of Plasmin
Plasmin is formed from inactivated glycoprotein called
plasminogen.
Plasminogen is synthesized in liver and it is
incorporated with other proteins in the blood clot.
Plasminogen is converted into plasmin by tissue
plasminogen activator (t-PA), lysosomal enzymes and
thrombin.
 The t-PA and lysosomal enzymes are released from
damaged tissues and damaged endothelium.
Thrombin is derived from blood. The t-PA is always
inhibited by a substance called t-PA inhibitor.
It is also inhibited by factors V and VIII. Besides t-PA,
there is another plasminogen activator called urokinase
plasminogen activator (u-PA). It is derived from blood.
Sequence of Events Involved in the
Activation of Plasminogen
1. During intravascular clotting, the endothelium of the
blood vessel secretes a thrombin-binding protein, the
thrombomodulin. It is secreted by the endothelium of all
the blood vessels, except the minute vessels of brain
2. Thrombomodulin combines with thrombin and forms
a thrombomodulin-thrombin complex
3. Thrombomodulin-thrombin complex activates protein
C
4. Activated protein C inactivates factor V and VIII in the
presence of a cofactor called protein S
5. Protein C also inactivates the t-PA inhibitor
 6. Now, the t-PA becomes active
7. Activated t-PA and lysosomal enzymes activate
plasminogen to form plasmin. Plasminogen is also
activated by thrombin and u-PA