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HAEMOSTASIS - I
DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
OBJECTIVES
 Haemostasis
 Blood coagulation
 Anti-haemostatic
mechanism
 Bleeding disorders.
 Laboratory tests.
Saturd...
HAEMOSTASIS
 Definition – spontaneous arrest or stoppage of bleeding
from injured blood vessel by physiological process.
...
VASOCONSTRICTION
 Immediate –
 Direct effect of injury
 Proportionate to the
degree of trauma.
 Later by humoral
 Rel...
FORMATION OF TEMPORARY
HAEMOSTATIC PLUG FORMATION
 Platelet adhesion
 Platelet activation
 Platelet aggregation
 Forma...
PLATELET ADHESION
 After injury platelets
contacts with collagen &
damaged endothelium
 Swell, becomes irregular &
protr...
PLATELET ACTIVATION
 Platelets secretes
 ADP & Thromboxane
A2
 Activates other
platelets & cycle
continues
Saturday, Ma...
PLATELET AGGREGATION
 Activated sticky
platelets stick to each
other & forms
Aggregation
 It is also increases by
Platel...
FORMATION OF TEMPORARY
HAEMOSTATIC PLUG
 Platelet Adhesion
 Platelet Aggregation
 Fairy Loose Plug
Saturday, May 14, 20...
INHIBITION OF FURTHER
PLUG FORMATION.
 Prostacycline from
membrane
phospholipids
 Inhibit Thromboxane
formation
Saturday...
FORMATION OF DEFINITIVE
HAEMOSTATIC PLUG FORMATION
 Temporary plug
converted to definitive
plug by Process of
blood coagu...
COAGULATION OF BLOOD
 Through out life blood – in
fluid state but when
removed or shed or
collected in container
become j...
COAGULATION OF BLOOD
 Clotting factors
 Mechanism of coagulation
 Role of calcium in blood coagulation.
 Role of vitam...
CLOTTING FACTORS
 I – FIBRINOGEN
 Soluble
 Mol wt – 3,40,000
Dalton
 6 polypeptide chain
 Conc. – 0.3 gm/100 ml
 It ...
CLOTTING FACTORS
 II- PROTHROMBIN
 Inactive precursor of
thrombin.
 Mol wt 69000 dalton.
 Synthesized in liver in
the ...
CLOTTING FACTORS
 III – THROMBOPLASTIN
 Also called tissue factor or tissue thromboplastin
 Released in extrinsic pathw...
CLOTTING FACTORS
 IV – CALCIUM
 Essential in all stages of coagulation.
Saturday, May 14, 2016
CLOTTING FACTORS
 V – LABILE FACTOR / PROACCLERIN
 Required for formation of protrombin activator
 Consumed during clot...
CLOTTING FACTORS
 VII – STABLE FACTOR / PROCONVERTIN
 For activation of factor X in extrinsic pathway.
Saturday, May 14,...
CLOTTING FACTORS
 VIII – ANTI-HAEMOPHYLLIC FACTOR A / ANTI-
HAEMOPHLIC GLOBULIN.
 Protein of b globulin type, synthesize...
CLOTTING FACTORS
 IX – ANTI-HAEMOPHILIC FACTOR B/ PLASMA
THROMBOPLASTIC COMPONENT
 First discovered in patient named Chr...
CLOTTING FACTORS
 X –STUART-PROWER FACTOR
 Along with active factor V, Ca and phopholipid forms a
complex – Prothrombin ...
CLOTTING FACTORS
 XI – PLASMA THROMBOPLASTIN
ANTICEDENT / ANTI-HAEMOPHILIC FACTOR C
 Its deficiency causes hemorrhagic s...
CLOTTING FACTORS
 XII – HAGEMAN FACTOR/ GLASS FACTOR /
CONTACT FACTOR
 Activated when comes in contact with electronegat...
CLOTTING FACTORS
 XIII – FIBRIN STABILIZING FACTOR /
FIBRINASE / LAKI LORAND FACTOR
 Required for activation of fibrin p...
Saturday, May 14, 2016
MECHANISM OF COAGULATION-
INTRINSIC PATHWAY.
Saturday, May 14, 2016
EXTRINSIC PATHWAY.
Saturday, May 14, 2016
DIFFERENCE .
 INTRINSIC
PATHWAY.
 Begins in blood itself.
 Much slower take 2-6
min.
 Initiated by activation
of facto...
CONVERSION OF
PROTHROMBIN TO THROMBIN
 Prothrombin –
 Inactive precursor of
thrombin.
 Mol wt 69000 dalton.
 Synthesiz...
THROMBIN.
Saturday, May 14, 2016
Proteolytic enzyme.
Amount of thrombin
produced during
clotting of 1 ml of
blood is suf...
I – FIBRINOGEN
 Soluble
 Mol wt – 3,40,000 Dalton
 6 polypeptide chain
 Conc. – 0.3 gm/100 ml
 It is converted into f...
FIBRINOGEN TO FIBRIN.
 Proteolysis
 Polymerization .
 Stabilization of fibrin polymers.
Saturday, May 14, 2016
BLOOD CLOT RETRACTION.
 Clot is meshwork of fibrin
with entrapped blood cells ,
platelets & plasma.
 Contractile protein...
ROLE OF CALCIUM.
 Except for first 2 steps Ca required for all steps.
 Ca removal causes Anticoagulation.
 e.g. use of ...
ROLE OF VITAMIN K.
 Chemical structure.
 Naphthoquinone derivatives.
 Fat soluble , insoluble in water.
 Sources.
 Fo...
ROLE OF VITAMIN K.
 Deficiency causes serious hemorrhages.
 Its due to
 Obstructive jaundice
 Newborn babies.
 Chroni...
ROLE OF LIVER.
 Synthesis of procoagulants – site of synthesis of
factor V,VII,IX,X, Prothrombin & fibrinogen
 Removal o...
ROLE OF BLOOD VESSELS.
 Endothelium
 Anticoagulant role.
 Barrier.
 Produces heparin & α-2
macroglobulin.
 Smoothness...
ROLE OF BLOOD VESSELS.
 Coagulant role
 Von Willebrand factor
(VWF)
 Tissue factor.
 Plasminogen activator.
 Sub endo...
BLOOD IN FLUID STATE
 Velocity of circulation.
 Surface effect of
endothelium.
 Glycocalyx
 Circulatory
anticoagulants...
VELOCITY OF CIRCULATION.
 Blood is in constant motion due to pumping by
heart & at constant velocity
 Decrease in veloci...
SURFACE EFFECT OF ENDOTHELIUM.
GLYCOCALYX
 Endothelial lining smoothness – prevents adhesion
& intrinsic mechanism.
 Gly...
CIRCULATORY ANTICOAGULANTS.
 Natural anti-coagulant.
 Heparin
 Antithrombin-III
 Alpha 2 macroglobulin
 Protein C
Sat...
FIBRINOLYTIC MECHANISM.
 Protein C
 Inactivates inhibitor of
TPA
 Increases Plasmin
formation
 Acts as Fibrinolytic
Sa...
REMOVAL OF ACTIVATED
CLOTTING FACTORS.
 Liver plays an important role
 Removes activated clotting factors
 Prevents Int...
THROMBOSIS
 Def.– Intravascular
clotting of blood & clot
so formed is thrombus
 Thrombus – Def –
Solid mass formed in
th...
THROMBOSIS
 Virchow’s triad which
predisposes to
thrombus formation.
 Predisposing factors
 Endothelial injury
 Altera...
ENDOTHELIAL INJURY
 It occurs in
 Ulcerated plaques in
advanced
atherosclerosis,
 Haemodynamic stress in
HT
 Arterial ...
ALTERATION OF BLOOD FLOW
 Turbulence / stasis blood
flow
 Platelet contact with
endothelium
 Initiate thrombosis
(espec...
HYPERCOAGULABILITY OF
BLOOD
 Increase Platelet count
& adhesiveness.
 Increase Coagulation
factors as fibrinogen,
prothr...
THROMBOGENESIS
 Adherence of platelets
 Activation of coagulation system
 Entanglement of RBC with WBC – so clot mass i...
THROMBI
 Red - mainly venous
 Soft, red & Gelatinous
 White – mainly arterial
 Pale & firm
 Mixed or laminated –
cons...
EFFECTS OF THROMBI
 Ischemia and Infarction
 Clot in Intact vessel decrease blood supply (Ischemia)
 Cell death (Infarc...
PREVENTION OF THROMBI
 Drugs – decrease platelet adhesion; Aspirin,
Dextran
 Anticoagulants – Heparin, Dicoumarol
 Inte...
Thank you.
Saturday, May 14, 2016
Saturday, May 14, 2016
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HAEMOSTASIS COAGULATION OF BLOOD

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HAEMOSTASIS COAGULATION OF BLOOD

  1. 1. HAEMOSTASIS - I DR NILESH KATE MBBS,MD ASSOCIATE PROF DEPT. OF PHYSIOLOGY
  2. 2. OBJECTIVES  Haemostasis  Blood coagulation  Anti-haemostatic mechanism  Bleeding disorders.  Laboratory tests. Saturday, May 14, 2016
  3. 3. HAEMOSTASIS  Definition – spontaneous arrest or stoppage of bleeding from injured blood vessel by physiological process.  3 processes  Vasoconstriction  Formation of temporary haemostatic plug formation  Formation of Definitive haemostatic plug formation Saturday, May 14, 2016
  4. 4. VASOCONSTRICTION  Immediate –  Direct effect of injury  Proportionate to the degree of trauma.  Later by humoral  Release of 5- HT by bound platelets to the collagen Saturday, May 14, 2016
  5. 5. FORMATION OF TEMPORARY HAEMOSTATIC PLUG FORMATION  Platelet adhesion  Platelet activation  Platelet aggregation  Formation of temporary haemostatic plug  Inhibition of further plug formation. Saturday, May 14, 2016
  6. 6. PLATELET ADHESION  After injury platelets contacts with collagen & damaged endothelium  Swell, becomes irregular & protrudes Pseudopodia.  Contractile proteins contracts & releases granules.  Platelets becomes sticky & adhere to collagen. Saturday, May 14, 2016
  7. 7. PLATELET ACTIVATION  Platelets secretes  ADP & Thromboxane A2  Activates other platelets & cycle continues Saturday, May 14, 2016
  8. 8. PLATELET AGGREGATION  Activated sticky platelets stick to each other & forms Aggregation  It is also increases by Platelet Activating Factor (PAF) released by neutrophils, Monocyte & platelets cell membrane lipids. Saturday, May 14, 2016
  9. 9. FORMATION OF TEMPORARY HAEMOSTATIC PLUG  Platelet Adhesion  Platelet Aggregation  Fairy Loose Plug Saturday, May 14, 2016
  10. 10. INHIBITION OF FURTHER PLUG FORMATION.  Prostacycline from membrane phospholipids  Inhibit Thromboxane formation Saturday, May 14, 2016
  11. 11. FORMATION OF DEFINITIVE HAEMOSTATIC PLUG FORMATION  Temporary plug converted to definitive plug by Process of blood coagulation.  Results in formation of tight unyielding seal Saturday, May 14, 2016
  12. 12. COAGULATION OF BLOOD  Through out life blood – in fluid state but when removed or shed or collected in container become jelly like – clot  Fluidity – necessary for circulation.  Coagulation – protect from excessive bleeding. Saturday, May 14, 2016
  13. 13. COAGULATION OF BLOOD  Clotting factors  Mechanism of coagulation  Role of calcium in blood coagulation.  Role of vitamin –k, liver and vascular wall in haemostasis and coagulation.  Blood clot retraction  Blood in fluid state  Thrombosis Saturday, May 14, 2016
  14. 14. CLOTTING FACTORS  I – FIBRINOGEN  Soluble  Mol wt – 3,40,000 Dalton  6 polypeptide chain  Conc. – 0.3 gm/100 ml  It is converted into fibrin in the presence of enzyme thrombin Saturday, May 14, 2016
  15. 15. CLOTTING FACTORS  II- PROTHROMBIN  Inactive precursor of thrombin.  Mol wt 69000 dalton.  Synthesized in liver in the presence of vitamin K.  Conc. is 40 mg / 100 ml. Saturday, May 14, 2016
  16. 16. CLOTTING FACTORS  III – THROMBOPLASTIN  Also called tissue factor or tissue thromboplastin  Released in extrinsic pathway. Saturday, May 14, 2016
  17. 17. CLOTTING FACTORS  IV – CALCIUM  Essential in all stages of coagulation. Saturday, May 14, 2016
  18. 18. CLOTTING FACTORS  V – LABILE FACTOR / PROACCLERIN  Required for formation of protrombin activator  Consumed during clotting so absent in serum. Saturday, May 14, 2016
  19. 19. CLOTTING FACTORS  VII – STABLE FACTOR / PROCONVERTIN  For activation of factor X in extrinsic pathway. Saturday, May 14, 2016
  20. 20. CLOTTING FACTORS  VIII – ANTI-HAEMOPHYLLIC FACTOR A / ANTI- HAEMOPHLIC GLOBULIN.  Protein of b globulin type, synthesized in liver.  Activation of factor x  Deficiency causes classical Haemophilia.  Inherited disease in which CT prolonged. Saturday, May 14, 2016
  21. 21. CLOTTING FACTORS  IX – ANTI-HAEMOPHILIC FACTOR B/ PLASMA THROMBOPLASTIC COMPONENT  First discovered in patient named Christmas. Saturday, May 14, 2016
  22. 22. CLOTTING FACTORS  X –STUART-PROWER FACTOR  Along with active factor V, Ca and phopholipid forms a complex – Prothrombin activator.  Formed in both extrinsic & intrinsic pathway. Saturday, May 14, 2016
  23. 23. CLOTTING FACTORS  XI – PLASMA THROMBOPLASTIN ANTICEDENT / ANTI-HAEMOPHILIC FACTOR C  Its deficiency causes hemorrhagic state. Saturday, May 14, 2016
  24. 24. CLOTTING FACTORS  XII – HAGEMAN FACTOR/ GLASS FACTOR / CONTACT FACTOR  Activated when comes in contact with electronegative surface or glass or rough surface.  Its activation initiate intrinsic pathway. Saturday, May 14, 2016
  25. 25. CLOTTING FACTORS  XIII – FIBRIN STABILIZING FACTOR / FIBRINASE / LAKI LORAND FACTOR  Required for activation of fibrin polymer along with Ca. Saturday, May 14, 2016
  26. 26. Saturday, May 14, 2016
  27. 27. MECHANISM OF COAGULATION- INTRINSIC PATHWAY. Saturday, May 14, 2016
  28. 28. EXTRINSIC PATHWAY. Saturday, May 14, 2016
  29. 29. DIFFERENCE .  INTRINSIC PATHWAY.  Begins in blood itself.  Much slower take 2-6 min.  Initiated by activation of factor XII.  EXTRINSIC PATHWAY.  Begins with trauma to the vascular wall or tissue outside the vessel wall.  Explosive in nature takes 15 sec.  Initiated by activation of factor III. Saturday, May 14, 2016
  30. 30. CONVERSION OF PROTHROMBIN TO THROMBIN  Prothrombin –  Inactive precursor of thrombin.  Mol wt 69000 dalton.  Synthesized in liver in the presence of vitamin K.  Conc. is 40 mg / 100 ml. Saturday, May 14, 2016
  31. 31. THROMBIN. Saturday, May 14, 2016 Proteolytic enzyme. Amount of thrombin produced during clotting of 1 ml of blood is sufficient to coagulate 3 liters of blood.
  32. 32. I – FIBRINOGEN  Soluble  Mol wt – 3,40,000 Dalton  6 polypeptide chain  Conc. – 0.3 gm/100 ml  It is converted into fibrin in the presence of enzyme thrombin Saturday, May 14, 2016
  33. 33. FIBRINOGEN TO FIBRIN.  Proteolysis  Polymerization .  Stabilization of fibrin polymers. Saturday, May 14, 2016
  34. 34. BLOOD CLOT RETRACTION.  Clot is meshwork of fibrin with entrapped blood cells , platelets & plasma.  Contractile proteins – Actin, myosin & thrombosthenin.  Compress fibrin meshwork squeeze out serum.  Clot reduced to 40% of original volume. Saturday, May 14, 2016
  35. 35. ROLE OF CALCIUM.  Except for first 2 steps Ca required for all steps.  Ca removal causes Anticoagulation.  e.g. use of oxalates & citrates. Saturday, May 14, 2016
  36. 36. ROLE OF VITAMIN K.  Chemical structure.  Naphthoquinone derivatives.  Fat soluble , insoluble in water.  Sources.  Food , bacterial flora.  Role of vitamin K  Synthesis of coagulants like Prothrombin.  Factor VII , IX & X & circulatory anticoagulant protein. Saturday, May 14, 2016
  37. 37. ROLE OF VITAMIN K.  Deficiency causes serious hemorrhages.  Its due to  Obstructive jaundice  Newborn babies.  Chronic diarrhoea.  Side effects of antibiotics. Saturday, May 14, 2016
  38. 38. ROLE OF LIVER.  Synthesis of procoagulants – site of synthesis of factor V,VII,IX,X, Prothrombin & fibrinogen  Removal of activated procoagulants.  Synthesis of anticoagulants like – heparin, anti thrombin III & protein C Saturday, May 14, 2016
  39. 39. ROLE OF BLOOD VESSELS.  Endothelium  Anticoagulant role.  Barrier.  Produces heparin & α-2 macroglobulin.  Smoothness prevent aggregation.  Produces PGI2 prevent aggregation. Saturday, May 14, 2016
  40. 40. ROLE OF BLOOD VESSELS.  Coagulant role  Von Willebrand factor (VWF)  Tissue factor.  Plasminogen activator.  Sub endothelial tissue – collagen fibres  Causes platelet aggregation  Intrinsic pathway activation. Saturday, May 14, 2016
  41. 41. BLOOD IN FLUID STATE  Velocity of circulation.  Surface effect of endothelium.  Glycocalyx  Circulatory anticoagulants.  Fibrinolytic mechanism.  Removal of activated clotting factors. Saturday, May 14, 2016
  42. 42. VELOCITY OF CIRCULATION.  Blood is in constant motion due to pumping by heart & at constant velocity  Decrease in velocity  Intravascular clotting Saturday, May 14, 2016
  43. 43. SURFACE EFFECT OF ENDOTHELIUM. GLYCOCALYX  Endothelial lining smoothness – prevents adhesion & intrinsic mechanism.  Glycocalyx --inner layer of endothelium negatively charged repel clotting factors &Y platelets & prevent clotting.  Intact Endothelium – barrier between collagenous tissue & blood Saturday, May 14, 2016
  44. 44. CIRCULATORY ANTICOAGULANTS.  Natural anti-coagulant.  Heparin  Antithrombin-III  Alpha 2 macroglobulin  Protein C Saturday, May 14, 2016
  45. 45. FIBRINOLYTIC MECHANISM.  Protein C  Inactivates inhibitor of TPA  Increases Plasmin formation  Acts as Fibrinolytic Saturday, May 14, 2016
  46. 46. REMOVAL OF ACTIVATED CLOTTING FACTORS.  Liver plays an important role  Removes activated clotting factors  Prevents Intravascular Clotting Saturday, May 14, 2016
  47. 47. THROMBOSIS  Def.– Intravascular clotting of blood & clot so formed is thrombus  Thrombus – Def – Solid mass formed in the living heart or blood vessel from the constituents of blood. Saturday, May 14, 2016
  48. 48. THROMBOSIS  Virchow’s triad which predisposes to thrombus formation.  Predisposing factors  Endothelial injury  Alteration of blood flow  Hypercoagulability of blood Saturday, May 14, 2016
  49. 49. ENDOTHELIAL INJURY  It occurs in  Ulcerated plaques in advanced atherosclerosis,  Haemodynamic stress in HT  Arterial diseases  DM  Hypercholesterolemia Saturday, May 14, 2016
  50. 50. ALTERATION OF BLOOD FLOW  Turbulence / stasis blood flow  Platelet contact with endothelium  Initiate thrombosis (especially venous thrombosis in leg veins after major operations) Saturday, May 14, 2016
  51. 51. HYPERCOAGULABILITY OF BLOOD  Increase Platelet count & adhesiveness.  Increase Coagulation factors as fibrinogen, prothrombin factors,Via,VIIa,Xa  Decrease coagulation inhibitors – Antithrombin III & fibrinogen degradation product. Saturday, May 14, 2016
  52. 52. THROMBOGENESIS  Adherence of platelets  Activation of coagulation system  Entanglement of RBC with WBC – so clot mass is mainly formed by entangled RBC & WBC. Saturday, May 14, 2016
  53. 53. THROMBI  Red - mainly venous  Soft, red & Gelatinous  White – mainly arterial  Pale & firm  Mixed or laminated – consists of alternate white & red Layers – Lines Of Zahn. Saturday, May 14, 2016
  54. 54. EFFECTS OF THROMBI  Ischemia and Infarction  Clot in Intact vessel decrease blood supply (Ischemia)  Cell death (Infarction)  Thromboembolism  Dislodged clot in distant vessel & block circulation  Pulmonary & Cerebral Embolism Saturday, May 14, 2016
  55. 55. PREVENTION OF THROMBI  Drugs – decrease platelet adhesion; Aspirin, Dextran  Anticoagulants – Heparin, Dicoumarol  Intermittent compression or electrical stimulation of calf muscle Saturday, May 14, 2016
  56. 56. Thank you. Saturday, May 14, 2016
  57. 57. Saturday, May 14, 2016
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HAEMOSTASIS, COAGULATION OF BLOOD

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