HAEMOSTASIS

OVERVIEW
By the end of this presentation, we should understand
mechanisms in;
 Haemostasis

 Intravascular clot formation

 Fibrinolysis
(II) HAEMOSTASIS

May 29, 2024

 Haemostasis
-Prevention of blood loss
-spontaneous arrest or stoppage of bleeding from

Hemostasis & Blood coagulation

injured blood vessel by physiological process.
-It is achieved by
 Vascular spasm
 Formation of platelet plug

 Formation of blood clot

 Growth of fibrous tissues into the clot to close the hole in the blood

vessel

3
VASCULAR CONSTRICTION

May 29, 2024

 After blood vessel injury
 Walls of the vessel contract due to
 Nervous reflex initiated by

Hemostasis & Blood coagulation

 Pain or other tissue factors

 Release of serotonin and other vasoconstrictors by platelets

 Local myogenic spasm

 Local humoral factors from injured tissue

4
VASCULAR CONSTRICTION

May 29, 2024

 For smaller vessels
 Platelets are responsible for much of the contraction
 Release vasoconstrictor substances
 Such as Thromboxane A

Hemostasis & Blood coagulation

 Vascular spasm can last
 Formany minutes to hrs
 During this time formation of platelet plug takes place

5
PLATELET PLUG

May 29, 2024

 When platelets come in contact with damaged vascular
surface
 They become activated
 Swell, form pseudopodia

Hemostasis & Blood coagulation

 Contractile protein contract causing

 Release of granules

 They become sticky and stick to collagens

 They release large quantities of Thromboxane A which

2
 Enhance platelets aggregation

7
PLATELET PLUG

May 29, 2024

 Aggregated platelets form
 Platelet plug which at first
 Is loose but can block blood loss

Hemostasis & Blood coagulation

 Subsequently fibrin threads develop
 Attach to platelets
 Construct a tight plug

 If the vessel damage is small

 Platelet plug is enough to block blood loss
 But if the hole is big then
 Blood clot formation is required to block blood loss

8
PLATELET PLUG

May 29, 2024

 If a person has few platelets then
 Plug formation is impaired
 Develops small bleeding spots under the skin and through out

Hemostasis & Blood coagulation

internal tissues
 Thrombocytopenic purpura

9
 Reactions involved in haemostasis

Blood vessel injury

May 29, 2024

Collagen Thromboplastin
Contraction

Hemostasis & Blood coagulation

Platelets Activation of
reaction coagulation

Loose
Platelets Thrombin
plug

Temporally Definitive haemostatic plug

haemostatic plug

Limiting factors
10
FORMATION OF BLOOD CLOT

May 29, 2024

 Clot formation
 Begins 15 to 20 sec after injury
 Activator substances

Hemostasis & Blood coagulation

 From traumatized vessel,
 Adhere to traumatized vascular wall
 Platelet aggregation

 Fibrinogen converted to fibrin fibres

 Clot formation, and retraction

11
FORMATION OF CLOT

May 29, 2024

 3 to 6 minutes after rapture
 Vessel opening is filled with clot
 After 20 minutes to an hr

Hemostasis & Blood coagulation

 Clot retraction occurs
 Platelets are necessary for clot retraction

12
FORMATION OF CLOT

May 29, 2024

 Platelets attach to fibrin fibres
 Releasefibrin stabilizing factor
 Cause more fibrin fibres to attach to one another

Hemostasis & Blood coagulation

 Platelets activate
 Actin, myosin, thrombosthenin
 Cause contraction of platelets together with the attached fibres

13
FORMATION OF CLOT

May 29, 2024

 This causes compression of fibrin mesh into smaller mass
 This squeezes most of the fluid out (serum)
 All its fibrinogen and clotting factor have been removed

 Hence serum does not clot

Hemostasis & Blood coagulation

14
THE FATE OF THE FORMED CLOT

May 29, 2024

 It can be invaded by fibroblasts
 Formation of connective tissue
 Promoted by growth factor from platelets

Hemostasis & Blood coagulation

 This continues until
 Clot is organized into fibrous tissue

15
THE FATE OF FORMED CLOT

May 29, 2024

 Fate of the clot
 Clot can be dissolved by the action of special substances

Hemostasis & Blood coagulation

16
MECHANISMS OF BLOOD
COAGULATION

May 29, 2024

 Within the blood there are
 Substances that promote blood coagulation
 Pro-coagulants

Hemostasis & Blood coagulation

 Substances that inhibit blood coagulation
 Anticoagulants
 Whether blood coagulates or not
 Depends on the balance between the activity of the
two system
 Anticoagulants usually predominate
 Blood does not coagulate

17
MECHANISMS OF BLOOD
COAGULATION

May 29, 2024

 When blood vessel is damaged
 Pro-coagulant in the damaged area become activated and
override the anticoagulants

Hemostasis & Blood coagulation

 Clot formation develops

18
GENERAL MECHANISM
Vessel injury

Prothrombin
Prothrombin  Blood coagulation
Prothrombin
activator + takes place in 3 steps
Ca++
Thrombin
Thrombin  First step

Factor XIIIa, Ca++

 In response to vessel
injury
Fibrinogen
Fibrinogen Fibrin
Fibrin
 Complex cascade of
chemical reaction occur

May 29, 2024 Hemostasis & Blood coagulation 19

GENERAL MECHANISM
Vessel injury

Prothrombin
Prothrombin
 Result in activated
Prothrombi
n activator substances
+ Ca++  Prothrombin activator
Thrombin
Thrombin
 Second step
Factor XIIIa, Ca++
 Prothrombin activator
 In the presence of ca++
Fibrinogen
Fibrinogen Fibrin
Fibrin catalyze the conversion of
prothrombin to thrombin

May 29, 2024 Hemostasis & Blood coagulation 20

GENERAL MECHANISM
Vessel injury

Prothrombin
Prothrombin
 Third step
Prothrombi  Thrombin acts as an enzyme
n activator
+ Ca++
to
 Convert fribrinogen to
Thrombin
Thrombin
fibrin fibres
Factor XIIIa, Ca++  Traps RBC, platelets,
plasma proteins
 Formation of clot
Fibrinogen
Fibrinogen Fibrin
Fibrin

May 29, 2024 Hemostasis & Blood coagulation 21

GENERAL MECHANISM
Vessel injury
 Platelets play an important
Prothrombin
Prothrombin
Prothrombi role in the conversion of
n activator prothrombin to thrombin
+ Ca++  Prothrombin
Thrombin
Thrombin
 Binds to platelets that are
already bound to the
Factor XIIIa, Ca++
damaged tissue
 This accelerates the

Fibrinogen Fibrin
formation of thrombin
Fibrinogen Fibrin
from prothrombin

May 29, 2024 Hemostasis & Blood coagulation 22

PROTHROMBIN & THROMBIN

May 29, 2024

 Prothrombin is a plasma protein
 2 globulin, MW 68,700
 conc in plasma = 15 mg/dl

Hemostasis & Blood coagulation

 It is an unstable compound
 Splits easily to smaller compounds
 Thrombin being one of them
 It is formed by the liver
 Require vitamin K for the formation

23
CONVERSION OF FIBRINOGEN
TO FIBRIN

May 29, 2024

 Fibrinogen is a high mol wt protein, MW
340,000
 Found in plasma at a conc 100 - 700 mg/dl

Hemostasis & Blood coagulation

 It is also formed in the liver
 Because of its high MW
 It does not leak into interstitial space
 ISF does not clot

24
CONVERSION OF FIBRINOGEN
INTO FIBRIN

May 29, 2024

 Thrombin acts on fibrinogen to convert it into
fibrin
 Removes 4 low mol wt peptides from each mol of

Hemostasis & Blood coagulation

fibrinogen
 Forms mol of fibrin monomers which polymerize to form
 Fibrin fibres
 Fibrin activating factor, released by platelets
 Activated by thrombin
 Converts fibrin fibres into cross linked meshwork of fibrin

fibres

25
INITIATION OF COAGULATION

May 29, 2024

 Formation of Prothrombin activator
 prothrombin activator can be initiated by
 Trauma to the vascular walls and adjacent tissues

Hemostasis & Blood coagulation

 Trauma to blood
 Contact of blood with damaged endothethelium or collagen
 Contact of blood with other tissue elements outside the

vessels
 All these lead to the formation of prothrombin
activator
 Cause conversion of prothrombin to thrombin

27
INITIATION OF COAGULATION

May 29, 2024

 Prothrombin activator can be formed by two ways
 Extrinsic pathway
 Begins with trauma to vascular walls and the surrounding tissues

Hemostasis & Blood coagulation

 Intrinsic pathways
 Begins in the blood itself

28
INITIATION OF COAGULATION

May 29, 2024

 In both the extrinsic and intrinsic pathways
 Different plasma proteins (  globulins)
 Called blood clotting factors

Hemostasis & Blood coagulation

 Play major role in the formation of prothrombin activator

29
INITIATION OF COAGULATION

May 29, 2024

 The blood clotting factors are
 Inactive proteolytic enzymes
 When activated they cause

Hemostasis & Blood coagulation

 Cascading reactions leading to the
 Activation of the various factors and
 Formation of prothrombin activator

30
CLOTTING FACTORS
NOMENCLATURE
Factor synonym

I Fibrinogen

II Prothrombin

III Tissue factor, tissue thromboplastin

IV C++

V Proaccelerin, labile factor, accelerator – Globulin (Ac-G)

VII Serum Prothrombin Conversion Accelerator (SPCA), procorventin,

stable factor

May 29, 2024 Hemostasis & Blood coagulation 31

CLOTTING FACTORS
NOMENCLATURE
Factor synonym

VIII Anti-hemophilic factor (AHF),anti-hemophilic globulin, anti-hemophilic

factor A
IX Plasma thromboplastin component (PTC), Christmas factor, anti-
hemophilic factor B
X Stuart factor, Stuart Prower factor

XI Plasma thromboplastin antecedent (PTA), anti-hemophilic factor C

XII Hageman factor

XIII Fibrin stabilizing factor

May 29, 2024 Hemostasis & Blood coagulation 32

CLOTTING FACTORS
NOMENCLATURE
Factor Synonym

Prekalikrein Fletcher factor

HMWK High molecular weight Kininoggen, Fitzgerald factor

Platelets Platelets phospholipids

May 29, 2024 Hemostasis & Blood coagulation 33

THE EXTRINSIC PATHWAYS

May 29, 2024

 Begins with traumatized vascular walls or extra vascular
tissue
 The traumatized tissue release tissue factor (tissue
thromboplastin)

Hemostasis & Blood coagulation

 Composed of phospholipids, lipoproteins complex containg
proteolytic enzymes
 Activation of factor X
 Lipoprotein complexes with
 Tissue factor, factor VII, Ca++
 This complex acts to convert
 X  Xa

34
THE EXTRINSIC PATHWAY

May 29, 2024

Formation of prothrombin activator
 Activated factor Xa
 Combine with tissue phospholipids, platelets

Hemostasis & Blood coagulation

phospholipids, factor V
 This complex is known as prothrombin activator
 FactorXa is the actual protease that split
prothrombin to thrombin
 Thrombin activate factor V
 Factor V and phospholipids accelerate the reaction

35
EXTRINSIC PATHWAY
INTRINSIC PATHWAY

May 29, 2024

 Begins with
 Trauma to blood itself or
 Exposure of blood to collagen in traumatized blood

Hemostasis & Blood coagulation

vessel
 Blood trauma causes
 Activation of factor XII
 Release of platelets phospholipids
 Activated factor XII in the presence of HMWK
 Activates factor XI

37
INTRINSIC PATHWAYS

May 29, 2024

 Activated
factor XI together with platelets
phospholipids, VIIIa , Ca++
 Activate factor factor IX

Hemostasis & Blood coagulation

 Activated factor IX together with
 VIIIa, platelets phospholipids
 Activates factor X
 After the activation of factor X
 Pathway proceed like in the extrinsic pathways to
cause the formation of thrombin

38
THE INTRINSIC PATHWAY
DIFFERENCE

INTRINSIC EXTRINSIC
PATHWAY. PATHWAY.
- Begins in blood itself. -Begins with trauma to
the vascular wall or
-Much slower take 2-6 tissue outside the
min. vessel wall.

-Initiated by activation -Explosive in nature

of factor XII. takes 15 sec.

-Initiated by activation
of factor III.
INTRA-VASCULAR
ANTICOAGULANTS

May 29, 2024

Factors involved in the prevention of coagulation
in the normal vascular system
1.Endothelial surface factors

Hemostasis & Blood coagulation

a. Smoothness of the endothelium prevent
 Contact activation of the intrinsic pathway
b. Layer of glycocalyx
 Present in the endothelium
 Repels clotting factors, platelets

 Prevents activation of clotting

41
INTRA-VASCULAR
ANTICOAGULANTS

May 29, 2024

c. Presence of thrombomodulin in endothelium
 Bind thrombin
 Combination of thrombin & thrombomodulin
Slows clotting

Hemostasis & Blood coagulation



 Activate plasma protein C

 Inactivates factor V, VIII
2. Action of fibrin and Antithrombin III
 Fibrin fibres
 Thrombin becomes attached to fibrin fibres
 This prevent spread of thrombin to neighbouring regions

42
INTRA-VASCULAR
ANTICOAGULANTS

May 29, 2024

 Antithrombin III
 Circulating protease inhibitor
 Binds to serine proteases in the coagulation system

Hemostasis & Blood coagulation

 Blocking their activity as coagulating factors

 Binding is facilitated by heparin

 Factors inhibited include

 IX, X, XI, XII
 It also binds and inactivates thrombin

43
INTRA-VASCULAR
ANTICOAGULANTS

May 29, 2024

3. Heparin
 Prodused by many different cells of the body mostly
from basophilic mast cells

Hemostasis & Blood coagulation

 Powerful anticoagulant
 Present in blood in small amounts
 By itself, it has little or no antcoagulant properties
 In combination with antithrombin III form powerful
inhibition of coagulation

44
FIBRINOLYTIC SYSTEM
Plasminogen  Function to dissolve the
activator clot after it has been
Fibrin ,
Thrombin formed
 System consist of
plasminogen plasmin proenzyme plasminogen
 Which is converted to the
active enzyme plasmin by
 Plasminogen activator
Fibrin Soluble fibrin  Tissue plasminogen activator
(t-PA)

May 29, 2024 Hemostasis & Blood coagulation 45

FIBRINOLYTIC SYSTEM
Plasminogen  Plasmin digest fibrin and
activator fibrinogen to
Fibrin ,
 Dissolve the clot
Thrombin
 Fibrinogen degradation

plasminogen plasmin
products (FDP)

Fibrin Soluble fibrin

May 29, 2024 Hemostasis & Blood coagulation 46

FIBRINOLYTIC SYSTEM
Plasminogen  Plasminogen activator
activator  Tissue plasminogen activator
Fibrin ,
Thrombin
(t-PA)
 Secreted by endothelial cells

Plasminogen Plasmin  During the clotting process

 Plasminogen & t-PA bind to
fibrin
 Increases the ability to
generate plasmin
Fibrin Soluble fibrin

May 29, 2024 Hemostasis & Blood coagulation 47

INHIBITION OF FIBRINOLYTIC
SYSTEM
Plasminogen  Plasminogen inhibitor
activator  2 -antiplasmin
Fibrin ,
Thrombin  Binds with plasmin and
inhibits it
Plasminogen Plasmin

2 antiplasmin

Fibrin Soluble fibrin

May 29, 2024 Hemostasis & Blood coagulation 48

THANK YOU