This document provides an overview of the physiology of blood coagulation. It discusses the structure and function of platelets, the clotting factors involved in coagulation, and the intrinsic and extrinsic pathways of coagulation. It also describes how fibrinogen is converted to fibrin to form a blood clot, as well as the roles of calcium, vitamins, and blood vessels. Mechanisms that prevent circulating blood from clotting and the anti-hemostatic factors involved are also summarized.

1. “PHYSIOLOGY OF
COAGULATION”
DR.A.BEEULA
1 MDS
DEPT.OF ORAL PATHOLOGY
Chettinad Dental College and RI

2. CONTENT:
PLATELETS
STRUCTURE
FUNCTION
FORMATION
NORMALVALUES
PROPERTIES
REGULATION
FATE OF PLATELETS
HAEMOSTASIS
MECHANISM
BLOOD
COAGULATION
CLOTTING FACTORS
MECHANISM:
INTRENSIC
PATRHWAY
EXTRENSIC
PATHWAY
BLOOD CLOT
RETRACTION
ROLE OF MINERALS
ANTIHAEMOSTATIC
MECHANISMS

3. WHAT IS COAGULATION?
• BLOOD REMAINS INTHE FLUID CONDITIONWITHINTHE BLOOD
VESSELSTHROUGHOUT LIFE,
• BUTWHENTHE BLOOD IS SHED FROMTHE BLOODVESSELS ARE
COLLECTED INTHE COINTAINER ,IT LOOSES ITS FLUIDITYWITHIN A FEW
MINUTES AND IS CONVERTEDTO JELLY-LIKE MASSWHICH IS CALLED
CLOT.
• THIS PHENOMENON IS CALLED COAGULATION OR CLOTTING OF
BLOOD.

4. WHY CIRCULATING BLOOD DOES NOT CLOT:

5. IMPORTANT COMPONENTS FOR BLOODTO
CLOT:
• PLATELETS
• CLOTTING FACTORS
• ROLE OF CALCIUM
• ROLE OFVITAMINS
• ROLE ON BLOODVESSELS

6. PLATELETS:

8. PLATELETS:
STRUCTURE AND COMPOSITION:
PLATELETS (SMALL PLATES)KNOWN ASTHROMBOCYTES.
[THROMBO=CLOT; CYTES=CELLS]

9. STRUCTUREAND COMPOSITION:
• SIZE:
PLATELETS ARE SMALLER BLOOD CELLS
DIAMETER: 2-4uM
VOLUME: 5.8uM3
• SHAPE AND COLOUR:
PLATELETS ARE COLOURLESS
SPHERICAL OR OVAL DISCOID STRUCTURES.

10. STRUCTUREAND COMPOSITION:
• LEISHMAN STAINING:
PLATELET CONSITS OF FAINT BLUISH CYTOPLASM
REDDISH PURPLE GRANULES
• NUCLEUS:
ABSENT[CANNOT REPRODUCE]

11. ELECTRON MICROSCOPIC STRUCTURE:
CELL MEMBRANE
MICROTUBULES
CYTOPLASM

12. CELL MEMBRANE
• IT CONSISTS OF LIPID,CARBOHYDRATES,PROTEINS,GLYCOPROTEINS
GLYCOPROTEINS:
FORMSTHE SURFACE COAT OFTHE PLATELET MEMBRANE
PREVENTS ADHERENCE OF PLATELETTO NORMAL ENDOTHELIUM
ACCELERATESTHE ADHERENCE OF PLATELETSTO COLLAGEN AND
DAMAGED ENDOTHELIUM IN INJURED BLOODVESSELS.

13. PHOSPOLIPIDS:
• PHOSPHOLIPIDS OFTHE PLATELET MEMBRANE CONTAIN PLATELET
FACTOR-3WHICH PLAYS AN IMPORTANT ROLE IN ACTIVATING ROLE IN
THE SEVERAL POINTS IN BLOOD CLOTTING PROCESS

14. CONTD…..
• INVAGINATION OFTHE SURFACE MEMBRANE FORMSTHE SO-CALLED
CANALICULAR SYSTEM ORTHE SURFACE CONNECTING SYSTEM
• RECEPTORS PRESENT ONTHE PLATELET MEMBRANE COMBAINS
WITH SPECIFIC SUBSTANCES LIKE COLLAGEN AND FIBRINOGEN.

15. PROPERTIES AND FUNCTION OF PLATELETS
• ADHESIVENESS
PLATELETS POSSESSTHE PROPERTY OF ADHESIVENESS
WHENTHEY COME IN CONTACT ANDWET SURFACE OR ROUGH
SURFACE ,THESE ARE ACTIVATED AND STICKTOTHE SURFACE
FACTORS RESPOSIBLE FOR ADHESIVENESS ARE : COLLAGEN,
THROMBIN, ADP ,THROMBOXANE A2 , Ca+ANDVON WILLEBRANT FACTOR

16. AGGREGARTION
• PLATELETS HAVETHE PROPERTYTO AGGREGATE
THEY STICKTO EACH OTHER
THIS IS DUETOATP ANDTHROMBAXANEA2

17. AGGLUTINATION
• CLUMBINGTOGETHER OF PLATELETS IS CALLED AGGLUTIONATION
THIS OCCURS DUETOTHE ACTIONS OF SOME PLATLETS AGGLUTININS

18. FUNCTIONS OF PLATELETS
ROLE IN HAEMOSTASIS
ROLE IN CLOT FORMATION
ROLE IN CLOT RETRACTION
ROLE IN REPAIR OF INJURED BLOODVESSELS
ROLE IN DEFENCE MECHANISAM
TRANSPORT AND STORAGE FUNCTIONS

19. NORMAL COUNT ANDVARIATIONS:
NORMAL COUNT RANGES FROM: 1,50,000/MM3 TO 4,50,000/MM3
AVERAGE COUNT : 2.5 LAC/MM3

20. PHGYSIOLOGICALVARIATIONS;
AGE LESS IN INFANTS(1 LAC – 2LAC/MM3)
ADULT LEVELS ARE REACHED BY 3RD MONTH OF AGE
SEX NORMALLY NO DIFFERENCE BETWEEN MALES AND FEMALES
DURING,MENSTRUATIONTHE COUNT IS REDUCED IN FEMALES
AFTER MEAL COUNT IS SLIGHTLY INCREASED
AFTER SEVERE
MUSCULAR
EXERCISE
MAY INCREASE
AT HIGH
ALTITUDE
COUNT IS INCREASED

21. FORMATION OF PLATELETS:
• FORMATION OR DEVELOPMENT OF PLATELETS IS CALLED
THROMBOPOIESIS
• THE PLATELETS ARE PRODUCED INTHE BONE MARROW
• THE PLURIPOTENT STEM CELLS FORMS PLATELETS IS CONVERTED
INTO COLONY FORMING UNITS CALLED “MEG-CFU”
• THROUGHVARIOUS STAGES IT DEVELOPS INTO PLATELET

22. STAGES IN PLATELET PRODUCTION:
PLURIPOTENT STEM CELLS
PROGENITOR CELL(MEGAKARYOBLAST)
ENDOREDUPLICATION
PROMEGAKARYOCYTES
MEGAKARYOCYTES
PLATELETS

23. MEGAKARYOBLAST:
• THE EARLIEST RECOGNIZABLE PRECURSOR OF PLATELETS INTHE
BONE MARROW IS MEGAKARYOBLAST
• IT ARISES FROM MEG-CFU BYTHE PROCESS OF DIFFERENTIATION
DIAMETER 20-30uM
CYTOPLASM SMALL,BLUE AND NON-GRANULAR
NUCLEUS LARGE ,OVAL OR KIDNEY SHAPED WITH
SEVERAL NUCLEOLI

25. PROMEGAKARYOCYTES:
• PROMEGAKARYOCYTE IS FORMED FROMTHE MEGAKARYOBLAST
• THE LARGE CELL CONTAINING UPTO 32TIMESTHE NORMAL DIPLOID
CONTENT OF NUCLEAR DNA IS FORMED
• WHEN FURTHER NUCLEAR REPLICATION CEASES ,CYTOPLASM
BECOMES GRANULAR
• THE GRANULES ARE BASICALLY BASOPHILIC

26. ENDOREDUPLICATION:
• THE MEGAKARYOBLAST UNDERGOES ENDOREDUPLICATION OF
NUCLEAR CHROMATIN
• I.E)NUCLEAR CHROMATIN REPLICATES REPEATEDLY IN MULTIPLES OF
TWOWITHOUT DIVISION OF CELLS.

27. MEGAKARYOCYTES:
THE PROMEGAKARYOCYTE MATURES INTO MEGAKARYOCYTE
• PLATELETSARE FORMED FROMTHE PSEUDOPODIAOF MEGAKARYOCYTECYTOPLASM
WHICH GETS DETACHED INTOTHE BLOOD STREAM
• EACH MEGAKARYOCYTES FORMS -4000PLATELETS
• THE FORMATION OF PLATELETS FROMTHE STEMCELLSTAKES ABOUT 10 DAYS
DIAMETER LARGE CELL-30-90uM
NUCLEUS SINGLE MULTILOBED[4-16]
NUCLEUSWITH COARSLYCLUMPED
CHROMATIN
CYTOPLASM ABUDENT,LIGHT BLUE IN COLOUR
RED –PURPLE GRANULES
CELL MARGIN IRREGULAR –MANY PSEUDOPODIA

30. CONTROL OFTHROMBOPOIESIS:
• THROMBOPOIESIS SEEMSTO BE REGULATED BY FOLLOWING HUMORAL
FACTORS:
THROMBOPOIETIN
MEGAKARYOCYTE-COLONY STIMULATING ACTIVITY[MEG-CSA]
• THE FACTOR STIMULATING THE SYNTHESIS AND RELEASE OFTHESE AGENTS ARE
NOTYET KNOWN

31. LIFE SPAN AND FATE OF PLATELETS:
• LIFE SPAN OF PLATELETSVARIES FROM 8-12 DAYSWITH AN AVERAGE
OF 10 DAYS.
• PLATELETS ARE DESTROYED BYTHETISSUE MACROPHAGES SYSTEM
IN SPLEEN.
[NOTE: SPLENOMEGALY:REDUCTION INTHE PLATELET COUNT
SPLENECTOMY:INCREASE IN PLATELET COUNT]

33. HAEMOSTASIS:
• HAMEMOSTASIS REFERSTO SPONTANEOUS ARREST OR PREVENTION
OF BLEEDING FROMTHE INJURED/DAMAGEDVESSELS BYTHE
PHYSIOLOGICAL PROCESS.
VASOCONSTRICTION
FORMATION OFTEMP.HAEMOSTATIC PLUG
FORMATION OFTHE DEFINITIVE HAEMOSTATIC CLOT

37. MICROSCOPICAL FEATURES:

41. COAGULATION:

42. HISTORY:
THEORIES OF
COAGULATION
JOHANNES
MULLER
1801-1858
FIBRINOGEN RUDOLF
VIRCHOW
1902
FACTORV PAUL OWRNER 1947
FACTOR IX STEPHEN
CHRISTMAS
1952
FACTOR XII HAGEMAN 1955

43. BLOOD COAGULATION:
• COAGULATION FORMS AN INDISPENSABLE DEFENCE AGAINST
EXCESSIVE BLEEDING FROMTHEWOUND
• THE PROCESS OF BLOOD COAGULATION CONSISTS OF A CASCADE OF
REACTIONS.
• THE FINAL PRODUCT IS FORMATION OF FIBRIN NETWORK

45. OTHERS;
• HMW-K HIGH MOLECULAR WEIGHT KININOGEN OR FITZGERALD
FACTOR
• PRE KA PREKALLIKREIN OR FLETCHER FACTOR
• KA KALLIKREIN
• PL PLATELET PGOSPHOLIPID

46. FACTOR I:
FIBRINOGEN:
• IT IS A SOLUBLE PLASMA PROTEIN
• MOLECULAR WGT: 3,40,000 DELTON
• SYNTHESIZED IN LIVER
• CONTAINS 6 POLY PEPTIDE CHAINS
• PLASMA CONC  0.3GM/100ML
• FIBRINOGEN ------------THROMBIN---------FIBRIN

47. FACTOR II:
PROTHROMBIN:
• IT IS A PLASMA PROTEIN[ALPHA 2 GLOBULIN]
• INACTIVE PRECURSOR OF ENZYMETHROMBIN
• MOLECULAR WGT: 69,000DELTON
• SYNTHESIZED IN LIVER WITHTHE PRESENCE OFVITAMIN-K
• PLASMA CONC 40MG/100ML

48. FACTOR III:
THROMBOPLASTIN:
• ALSO CALLEDTISSUE FACTOR ORTISSUETHROMBOPLASTIN
• RELEASED IN EXTRENSIC PATHWAY FORTHE FORMATION OF
PROTHROMBIN ACTIVATOR

49. FACTOR IV:
CALCIUM
• CALCIUM IONS ARE RESPONSIBLE FORTHE BLOOD COAGULATION
[NOTE:DISCUSSED IN MECHANISM IN DETAIL]

50. FACTORV:
LABILE FACTOR:
• ALSO CALLED PROACCELERIN
• UNSTABLE FACTOR OFTHE PLASMA
• PROTHROMBIN………………THROMBIN [EXTRENSIC AND INTRENSIC]
• CONSUMED DURING CLOTTING ,ABSENT IN SERUM

51. FACTORVII:
STABLE FACTOR:
• STABLE PROTEIN
• SYNTHESIZED IN LIVER IN PRESENCE OFVIT-K
• ACTIVATION OF FACTOR X IN EXTRENSIC PATHWAY
• NOT CONSUMED DURING CLOTTING, PRESENT IN SERUM AND PLASMA

52. FACTORVIII:
ANTI-HEMOPHILIC FACTOR:
• PROTEIN OF BETA 2 GLOBULINTYPE
• SYNTHESIZED IN LIVER
• ACTIVATION OF FACTOR X AND FORMATION OF PROTHROMBIN IN
INTRENSIC PATHWAY
• CONSUMED DURING CLOTTING
• ABSENT IN SERUM

53. FACTOR IX:
CHRISTMAS FACTOR:
• ALSO CALLED PLASMATHROMBOPLASTIN COMPONENT[PTC]/AUTO
PROTHROMBIN II
• SYNTHESIZED IN LIVER
• ACTIVATED BY XI a INTHE PRESENCE OF CA+
• FORMATION OF PROTHROMBIN ACTIVATOR INTHE INTRENSIC
PATHWAY

54. FACTOR X:
STAUART PROWER FACTOR:
• PROTEIN PRESENT IN PLASMA
• SYNTHESIZED IN LIVER
• ACTIVATED BY IX a INTHE PRESENCE OF FACTOR
VIII,CA+,PHOSPHOLIPIDS
• FORMS PROTHROMBIN ACTIVATOR COMPLEX (EXTRENSIC AND
INTRENSIC)

55. FACTOR XI:
PLASMATHROMBOPLASTIN ANTECEDENT:
• ACTIVATED BY XII a
• ACTIVATION OF IX INTHE PRESENCE OF CA2+ IN INTRENSIC PATHWAY

56. FACTOR XII:
HAGEMAN FACTOR:
• XII IS ACTIVATEDTO XII aWHEN IT COMES IN CONTACT WITH –VE
CHARGE OR FOREIGN BODIES OR ROUGH SURFACES
• FEEDBACK ACTIVATION

57. FACTOR XIII:
FIBRIN STABILIZING FACTOR:
• STABILIZES FIBRIN POLYMERS INTHE PRESENCE OF CA2+

58. MECHANISM OF COAGULATION:
• CLOT FORMATION IS INITIATED UNDER FOLLOWING SUTIATIONS:
TRAUMATOTHEVASCULARWALL AND ADJACENTTISSUE
TRAUMATO BLOOD
CONTACT OF BLOODTOTHE DAMAGED ENDOTHELIUM OR
COLLAGEN OR OTHERTISSUE ELEMENTS OUTSIDETHEVESSELS

59. THE PROCESS OF COAGULATION:
• FORMATION OF PROTHROMBIN ACTIVATOR
• CONVERSION OF PROTHROMBIN------------- THROMBIN
• CONVERSION OF FIBRINOGEN …………..….FIBRIN

60. FORMATION OF PROTHROMBIN ACTIVATOR:
EXTRINSIC PATHWAY
INTRINSIC PATHWAY

61. EXTRINSIC PATHWAY:
• RELEASE OFTISSUETHROMBOPLASTINS
• ACTIVATION OF FACTOR X--------X a
• EFFECTS OF X a ----------------------PROTHROMBIN

63. INTRINSIC PATHWAY:
• ACTIVATION FACTOR XII
• ACTIVATION FACTOR XI
• ACTIVATION FACTOR IX
• ACTIVATION FACTOR X
• FPRMATION OF PROTHROMBIN ACTIVATOR

66. CONVERSION OF FIBRINOGENTO FIBRIN:
• PROTEOLYSIS
• POLYMERIZATION
• STABILIZATION OFTHE FIBRIN POLYMER

69. CLOT RETRACTION:

70. WHY CIRCULATING BLOOD DOES NOT
CLOT?
VELOCITY OF CIRCULATION
SURFACE EFFECTS OF ENDOTHELIUM
CIRCULATING ANTI-COAGULANTS
FIBRINOLYTIC MECHANISM
REMOVAL OF ACTIVATED CLOTTING
FACTOR

71. ANTI-HEMOSTATIC MECHANISM:
• THE FACTORWHICH BALANCESTHETENDENCY OFTHE BLOODTO CLOT
INVIVO CONSTITUESTHE ANTI-HEMOSTATIC FACTOR

72. ANTI-HEMOSTATIC FACTOR:
• FACTOR PREVENTING PLATELET AGGREGATION
• FACTOR PREVENTING COAGULATION (CIRCULATING ANTI-COAGULANTS)
• FACTOR CAUSING FIBRINOLYSIS(FIBRINOLYTIC MECHANISM)

73. FACTORS PREVENTING PLATELET
AGGREGATION:
• PROSTACYCLIN:
ENDOGENOUS FACTOR
PREVENTS PLATELET AGGREGATION BY PREVENTING THE
THROMBOXANE A2 FORMATION

74. CIRCULATING ANTI-COAGULANTS:
• THE NATURAL ANTI-COAGULANTS CIRCULATING INTHE BLOOD
CONSTITUETHE ANTO-COAGULANT MECHANISM OFTHE BODY
HEPARIN
ANTITHROMBIN II
PROTEIN C

75. HEPARIN
• IT ISTHE POWERFULL NATURAL ACTING ANTI-COAGULANT’
• FIRST ISOLATED FROM LIVER SO,CALLED HEPARIN[HEPAR=LIVER]
• POLYSACCHARIDE CONTAINING SULPHATE GROUP
• MOLECULAR WEIGHT=15,000-18,000

76. SECRETION-HEPARIN:
• SECREATED BY BASOPHILS AND MAST CELLS
[PRESENT INVARIOUSTISSUES SUCH AS LIVER,LUNGS,TISSUE RICH IN C.T]

77. MECHANISM OF ACTION:
• IT IS PRESENT ONTHE LUMINAL SURFACE OFVASCULAR ENDOTHELIUM
PREVENTS ACTIVATION OF PROTHROMBINTOTHROMBIN
INHIBITSTHE ACTION OFTHROMBIN ON FIBRINOGEN
FACILITATESTHE ACTION OF ANTITHROMBIN III
[INHIBITSTHE ACTIVE FORMS OF CLOTTING FACTOR IX,X,XI,XII]

78. PROTEIN -C PATHWAY:

79. FIBRINOLYTIC MECHANISM:
• FIBRINOLYSIS REFERSTOTHE PROCESSTHAT BRINGS ABOUTTHE
DISSOLUTION OF FIBRIN.
• THE IMPORTANT COMPONENT OFTHE FIBRINOLYTIC SYSTEM IS
PLASMIN OR FIBRINOLYSIN
• PRESENT INTHE BLOOD IN AN INACTIVE FORM CALLED PLASMINOGEN
• ALSO CALLED PLASMIN SYSTEM

80. PGYSIOLOGICAL ROLE OF FIBRINOLYSIS
SYSTEM:
• CLEANINGTHE MINUTE CLOTS OFTINYVESSELS
• PROMOTE NORMAL HEALING PROCESS
• LIQUEFACTION OF MENSTRUAL CLOT
• LIQUEFACTION OF SPERMS INTHE EPIDIDYMIS

81. ANTI-COALULANTS:
• ANTICOAGULANTS REFERSTOTHE SUBSTANCES WHICH DELAY OR
PREVENTTHE PROCESS OF COAGULATION OF BLOOD
• TYPES:
ENDOGENOUS
EXOGENOUS

82. ENDOGENOUS ANTICOAGULANTS:
• WHICH IS SINTHESIZED INTHE BODY ITSELF:
HEPARIN
ANTITHROMBIN II
PROTEIN C

83. EXOGENOUS ANTICOAGULANTS:
• WHICH SHOULD BE ADMINISTERED OUTSIDE:
HEPARIN
CA2+ /DECALCIFYING AGENTS
VITAMIN –K ANTAGONIST
DEFIBRINATION SUBSTANCES
COLD

84. FOODS INVOLVED IN CLOTTING
MECHANISM:
• FOOD HIGH INVIT-E AND LOW INVIT-KWILLTHINYOUR BLOOD AND
CLOTTING IS DIFFICULT
• VIT-E -ALMONDS,HAZELNUTS

85. VITAMIN-K
• FOODS RICH INVIT-KWILL MAKETHICKEN BLOOD
• SOURCE:SPROUTS,SPINACH,GREEN TEA,EGGYOLK,SOYABEANS

86. HERBS AND SPICES:
• THE PRODUCTYOU SPRINKLE INYOUR
FOODS,CAYENNE,GARLIC,GINGER AND ONION ACTS AS BLOOD
THINNER

87. FATTY FISH:
• FISH LIKE SALMON,MACKEREL,TUNA,CONTAINS SIGNIFICANT AMOUNT
OF OMEGA 3 FATTY ACID
• THIS IS A BLOODTHINNER

89. SUMMARY:

90. REFERNCES:
• INDHU KURUNATEXT BOOK OF PHYSIOLOGY
• GYTONTEXT BOOK OF PHYSIOLOGY
• AK JAIN PRACTICAL PHYSIOLOGY
• ONLINEWEBSITE

91. THANKYOU
HAVE A NICE
DAY