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 The process by which Blood is maintained in fluid
state within the vessel walls and ability of the
system to prevent excessive blood loss upon
injury is terms as:
HOMOESTASIS: meaning,
 HOMOEO = SAME / LIKE
 STATIS = STANDING
HAEMOSTASIS
HAEMOSTASIS
Dr.Radfan Saleh
phD.Hematology &Immunohematology
Ass.prof. in Medical Laboratory
Taiz University
HAEMOSTASIS
 Hemostasis is accomplished by 2
mechanisms which work in a delicate
balance with one another.
 These mechanisms are:
 Coagulation
 Fibrinolysis
HAEMOSTASIS
Thrombosis Hemorrhage
COAGULATION FIBRINOLYSIS
Coagulation: Clotting of Blood
Fibrinolysis: Dissolution of Clot / Hemorrhage
What is coagulation
 Coagulation is clot formation. It is the mechanism
that stops blood from being lost from the vessels.
It works to form clots, which stops the flow of
blood from an injured area.
What is fibrinolysis
 It is the mechanism that dissolves the clots
once formed as the injury has healed.
COAGULATION
 Coagulation is a complex process
involving involving various stages
Component :
 VASCULAR SYSTEM
 PLATELETS
 COAGULATION SYSTEM
(A) VASCULAR SYSTEM
Platelet
Endothelial cells
lining blood vessel
Collagen
Maintenance of Normal Vascular Integrity
Blood flows Normally without sticking:
01) Adherence to vessel Wall
02) The thin layer of endothelial cell (lining the inner surface of vessels)
help to maintain a thrombo resistant surface / non thrombogenic
surface.
ROLE OF PLATELETS
 Platelet performs 3 important functions:
1) Support Vascular Integrity
 Platelets are -ve charged. The endothelial lining
also carries-ve charge. Also the endothelial lining is
Non-Thrombogenic.
 However during a vascular injury the endothelial
lining is peeled off thus exposing the inner
connective tissues (Subendothelial layer of
Collagen)
 As a result the platelets are stimulated, undergoes
change of shape and the platelets are attracted to
the site of injury or Blood Leakage.
ROLE OF PLATELETS
2) Aggregation - Haemostatic plug
As an immediate response to injury Platelets rush to
the site of injury and adhere to each other.
3) Other substances are released (endogenous)
Intrinsic ADP (adenosine diphosphate) & other
substances PF3 (Platelet Factor 3). ADP is energy
deriving molecule. This helps to attract more &
more platelets at the site of injury to form a
Hemostasis plug.
A Collagen
B
Change of Shapes
Vasoconstriction
Platelets
PRIMARY HEMOSTASIS
PF3 ADP
Thromboxane A2
C
D
Hemostastic Plug
SECONDARY HEMOSTASIS
Secondary Hemostasis starts when the coagulation system is
activated by substances (e.g. PF3) released at the time of blood
vessel injury.
Coagulation factors:
 There are 12 coagulation factors.
 They circulate in plasma as inactive form (cofactors or
procoagulants).
 They are protein in nature and or mostly synthesized in liver
(except calcium & F VIII - Von Wiillebrand).
 They are represented in Roman numbers (I, II….XIII).
 They have been numbered as per their order of discovery.
 Fibrinogen was discovered first - FI
 Prothrombin was discovered second - FII
 They work in CASCADE SYSTEM.
COAGULATION CASCADE
01) EXTRINSIC PATHWAY
02) INTRINSIC PATHWAY
03) COMMON PATHWAY
COAGULATION CASCADE
Intrinsic Pathway Extrinsic Pathway
Common Pathway
CLOT INSOLUBLE FIBRIN
The process of
coagulation or clot
formation is a
series of enzymatic
reactions where
one step leads
to the next
in the form
of a cascade
EXTRINSIC PATHWAY
Extrinsic Pathway
(Tissue Thromboplastin)
FVIIa FVII
FX
FXa
Ca+2
FV (Phospholipids + Ca+2)
Prothrombin
FII
Thrombin
FIIa
Fibrinogen
FI
Fibrin
CLOT
Extrinsic Pathway
 When any Body cell is injured, it releases a substance
called TISSUE THROMBOPLASTIN (FIII).
 FVII combines with Ca+2 to form a complex.
 FIII is a phospholipid which provides a base for
attachment of FVII & Ca+2.
 Tissue Thromboplastin is initiator of Extrinsic Pathway.
 Laboratory estimation is called PT - Prothrombin Time.
INTRINSIC PATHWAY
Intrinsic Pathway negatively charged
(contact with a surface)
FXII XIIa
FXI FXIa
Ca+2 HMWK
FIX FIXa
FVIII
Phospholipids & Ca+2
FX
+
FXa
Prothrombin
FII
Thrombin
FIIa
Fibrin (Soluble)
Fibrin
FI
Intrinsic Pathway
 Activation of Intrinsic Pathway is also called as
Contact Activation.
 In case of internal injury, the endothelial lining is
peeled-off, thus exposure of the inner connective
tissue layer. This layer along with its collagen and
elastin fibres (strong negatively charged surface)
acts as an activator for Factor XII.
 Aggregated Platelets injured endothelial lining,
Trypsin, Kallikrein, Plasmin and Kininogen also
activates Factor XII.
Intrinsic Pathway
Initial Contact Activation
Kallikrein Prekallikrein
HMWK HMWK
FXII FXIIa
HMWK
Ca+2
FXIa
FXI
Intrinsic Pathway Extrinsic Pathway
 Internal Stimulus
Platelets
 External Stimulus
 Factor XII-HMW Kininogen  Initiator is tissue
thromboplastin
 Contact activation
Negatively charged
surfaces
 Tissue / cell injury
 Delayed pathway  Short pathway / fastest
cascade
 e.g. a PTT activated partial
Thromboplastin Time Test
 e.g. PT Prothrombin Time Test
Common Pathway
Extrinsic Intrinsic
FX

FXa
Prothrombin
FII
Enzyme
Thrombin
(FIIa)
Ca+2
FXIII FXIIIa
Fibrinogen
(FI)
Fibrin (Monomer)
(Soluble)
Fibrin (Insoluble)
Ca+2
FIBRONOLYSIS
A clot is formed as a response to an injury. Once the
injured
tissue starts healing, the clot becomes redundant and has to
be dissolved.
The process of clot dissolution is called Fibrinolysis and the
systems is known as FIBRINOLYTIC SYSTEM.
2 important functions
1. To restrict fibrin (clot) formation to the area of injury.
2. To dissolve the clot through Fibrin Digestion.
FIBRINOLYTIC SYSTEM
 Fibronolysis is the last stage of coagulation.
 Means - Dissolution and localization of Fibrin Clot.
 Fibrinolysis system consists of Enzymes (Fibrinolytic
Enzymes) and its corresponding inhibitors; which are in
Fine Balance.
 Any disruption in the above Balance of the Fibrinolytic
System can result in Bleeding or Thrombosis.
 PLASMIN is a major Enzyme of Fibrinolytic system and
Fibrinolysis is mediated by activation of Plasminogen 
Plasmin.
ACTIVATION OF PLASMINOGEN 
PLASMIN
Intrinsic Activation: Factor XIIa and Kallikrien
serves as
Activators.
Extrinsic Activation: During injury (tissue activator
as
well as endothelial activator) e.g. Urokinase, passes
into the blood and activates plasminogen to
plasmin.
Thus, Therapeutically drugs like Urokinase &
Streptokinase are used to dissolve clot - tissue
Plasminogen Activators (tPA).

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Coagulation Haemostasis - Copy1.ppt

  • 1.  The process by which Blood is maintained in fluid state within the vessel walls and ability of the system to prevent excessive blood loss upon injury is terms as: HOMOESTASIS: meaning,  HOMOEO = SAME / LIKE  STATIS = STANDING HAEMOSTASIS HAEMOSTASIS Dr.Radfan Saleh phD.Hematology &Immunohematology Ass.prof. in Medical Laboratory Taiz University
  • 2. HAEMOSTASIS  Hemostasis is accomplished by 2 mechanisms which work in a delicate balance with one another.  These mechanisms are:  Coagulation  Fibrinolysis
  • 3. HAEMOSTASIS Thrombosis Hemorrhage COAGULATION FIBRINOLYSIS Coagulation: Clotting of Blood Fibrinolysis: Dissolution of Clot / Hemorrhage
  • 4. What is coagulation  Coagulation is clot formation. It is the mechanism that stops blood from being lost from the vessels. It works to form clots, which stops the flow of blood from an injured area.
  • 5. What is fibrinolysis  It is the mechanism that dissolves the clots once formed as the injury has healed.
  • 6. COAGULATION  Coagulation is a complex process involving involving various stages Component :  VASCULAR SYSTEM  PLATELETS  COAGULATION SYSTEM
  • 7. (A) VASCULAR SYSTEM Platelet Endothelial cells lining blood vessel Collagen Maintenance of Normal Vascular Integrity Blood flows Normally without sticking: 01) Adherence to vessel Wall 02) The thin layer of endothelial cell (lining the inner surface of vessels) help to maintain a thrombo resistant surface / non thrombogenic surface.
  • 8. ROLE OF PLATELETS  Platelet performs 3 important functions: 1) Support Vascular Integrity  Platelets are -ve charged. The endothelial lining also carries-ve charge. Also the endothelial lining is Non-Thrombogenic.  However during a vascular injury the endothelial lining is peeled off thus exposing the inner connective tissues (Subendothelial layer of Collagen)  As a result the platelets are stimulated, undergoes change of shape and the platelets are attracted to the site of injury or Blood Leakage.
  • 9. ROLE OF PLATELETS 2) Aggregation - Haemostatic plug As an immediate response to injury Platelets rush to the site of injury and adhere to each other. 3) Other substances are released (endogenous) Intrinsic ADP (adenosine diphosphate) & other substances PF3 (Platelet Factor 3). ADP is energy deriving molecule. This helps to attract more & more platelets at the site of injury to form a Hemostasis plug.
  • 10. A Collagen B Change of Shapes Vasoconstriction Platelets PRIMARY HEMOSTASIS
  • 12. SECONDARY HEMOSTASIS Secondary Hemostasis starts when the coagulation system is activated by substances (e.g. PF3) released at the time of blood vessel injury. Coagulation factors:  There are 12 coagulation factors.  They circulate in plasma as inactive form (cofactors or procoagulants).  They are protein in nature and or mostly synthesized in liver (except calcium & F VIII - Von Wiillebrand).  They are represented in Roman numbers (I, II….XIII).  They have been numbered as per their order of discovery.  Fibrinogen was discovered first - FI  Prothrombin was discovered second - FII  They work in CASCADE SYSTEM.
  • 13. COAGULATION CASCADE 01) EXTRINSIC PATHWAY 02) INTRINSIC PATHWAY 03) COMMON PATHWAY
  • 14. COAGULATION CASCADE Intrinsic Pathway Extrinsic Pathway Common Pathway CLOT INSOLUBLE FIBRIN The process of coagulation or clot formation is a series of enzymatic reactions where one step leads to the next in the form of a cascade
  • 15. EXTRINSIC PATHWAY Extrinsic Pathway (Tissue Thromboplastin) FVIIa FVII FX FXa Ca+2 FV (Phospholipids + Ca+2) Prothrombin FII Thrombin FIIa Fibrinogen FI Fibrin CLOT
  • 16. Extrinsic Pathway  When any Body cell is injured, it releases a substance called TISSUE THROMBOPLASTIN (FIII).  FVII combines with Ca+2 to form a complex.  FIII is a phospholipid which provides a base for attachment of FVII & Ca+2.  Tissue Thromboplastin is initiator of Extrinsic Pathway.  Laboratory estimation is called PT - Prothrombin Time.
  • 17. INTRINSIC PATHWAY Intrinsic Pathway negatively charged (contact with a surface) FXII XIIa FXI FXIa Ca+2 HMWK FIX FIXa FVIII Phospholipids & Ca+2 FX + FXa Prothrombin FII Thrombin FIIa Fibrin (Soluble) Fibrin FI
  • 18. Intrinsic Pathway  Activation of Intrinsic Pathway is also called as Contact Activation.  In case of internal injury, the endothelial lining is peeled-off, thus exposure of the inner connective tissue layer. This layer along with its collagen and elastin fibres (strong negatively charged surface) acts as an activator for Factor XII.  Aggregated Platelets injured endothelial lining, Trypsin, Kallikrein, Plasmin and Kininogen also activates Factor XII.
  • 19. Intrinsic Pathway Initial Contact Activation Kallikrein Prekallikrein HMWK HMWK FXII FXIIa HMWK Ca+2 FXIa FXI
  • 20. Intrinsic Pathway Extrinsic Pathway  Internal Stimulus Platelets  External Stimulus  Factor XII-HMW Kininogen  Initiator is tissue thromboplastin  Contact activation Negatively charged surfaces  Tissue / cell injury  Delayed pathway  Short pathway / fastest cascade  e.g. a PTT activated partial Thromboplastin Time Test  e.g. PT Prothrombin Time Test
  • 21. Common Pathway Extrinsic Intrinsic FX  FXa Prothrombin FII Enzyme Thrombin (FIIa) Ca+2 FXIII FXIIIa Fibrinogen (FI) Fibrin (Monomer) (Soluble) Fibrin (Insoluble) Ca+2
  • 22. FIBRONOLYSIS A clot is formed as a response to an injury. Once the injured tissue starts healing, the clot becomes redundant and has to be dissolved. The process of clot dissolution is called Fibrinolysis and the systems is known as FIBRINOLYTIC SYSTEM. 2 important functions 1. To restrict fibrin (clot) formation to the area of injury. 2. To dissolve the clot through Fibrin Digestion.
  • 23. FIBRINOLYTIC SYSTEM  Fibronolysis is the last stage of coagulation.  Means - Dissolution and localization of Fibrin Clot.  Fibrinolysis system consists of Enzymes (Fibrinolytic Enzymes) and its corresponding inhibitors; which are in Fine Balance.  Any disruption in the above Balance of the Fibrinolytic System can result in Bleeding or Thrombosis.  PLASMIN is a major Enzyme of Fibrinolytic system and Fibrinolysis is mediated by activation of Plasminogen  Plasmin.
  • 24. ACTIVATION OF PLASMINOGEN  PLASMIN Intrinsic Activation: Factor XIIa and Kallikrien serves as Activators. Extrinsic Activation: During injury (tissue activator as well as endothelial activator) e.g. Urokinase, passes into the blood and activates plasminogen to plasmin. Thus, Therapeutically drugs like Urokinase & Streptokinase are used to dissolve clot - tissue Plasminogen Activators (tPA).