BLOOD CLOTTING MACHANISM

1. ANIMAL PHYSIOLOGY
BLOOD CLOTTING MECHANISM
Dr.J.PRAKASH SAHAYA LEON,M.Sc.,B.Ed.,M.Phil.,Ph.D.,
ASST. PROFESSOR, DEPARTMENT OF ZOOLOGY,
GOVERNMENT ARTS COLLEGE FOR MEN,
KRISHNAGIRI, TAMILNADU,INDIA
( DEPUTED FROM ANNAMALAI UNIVERSITY)

2. ANIMAL PHYSIOLOGY
BLOOD CLOTTING MECHANISM


3. INTRODUCTION
THE MOVEMENT OF BODY FLUID ( BLOOD AND
LYMPH) FROM ONE PART OF THE BODY TO OTHER
PARTS IS CALLED CIRCULATION.
 THE CIRCULATION OF BLOOD IN THE BLOOD
VESSELS WAS DISCOVERED BY WILLIAM-
HARWEY.
 IN MAMMALS THE CIRCULATORY SYSTEM
CONSISTS OF A HEART AND A SET OF BLOOD
VESSELS.

4. BLOOD COAGULATION (CLOTTING)
 THE CONVERSION OF LIQUID BLOOD INTO SEMISOLID AT
THE BLEEDING SITE IS CALLED COAGULATION ALSO
CALLED CLOTTING.
 THE SEMI SOLID BLOOD IS CALLED CLOT.
 CLOTTS PREVENTING THE FURTHER FLOW OF BLOOD
FROM THE CUT AREA, THUS THE CLOT ACTS AS A PLUG.
 THE PORTION OF THE BLOOD CLOT AREA SHOWS NUMBER
OF THREAD LIKE STRUCTURES FORMING A NETWORK
WHICH IS FORMED OF A PROTEIN CALLED FIBRIN.
 IN THE MESHES OF THE THREADS RBC AND WBC ARE SEEN
ENTANGLED.

5. MECHANISM OF CLOTTING
 THE SCHEME OF CLOTTING WAS PROPOSED IN 1903 BY
MORAWITZ.
 WHEN BLOOD IS SHED, THE PLATELETS (THROMBOPLASTS)
DISINTEGRATE AND LIBERATE THROMBOPLASTIN.
 SOME AMOUNT OF THROMBOPLASTIN IS ALSO DERIVED
FROM THE DAMAGED TISSUES.
 THROMBOPLASTIN THEN CONVERTS PROTHROMBIN INTO
ACTIVE THROMBIN WITH THE HELP OF CA++ IONS.
 THEN THE THROMBIN INTERACTS WITH FIBRINOGEN
FORMING FIBRIN, WHICH IS THE CLOT.
 1. THROMBOPLASTIN+PROTHROMBIN + CA++ THROMBIN
 2. THROMBIN + FIBRINOGEN FIBRIN ( BLOOD CLOT )

6. BEST AND TAYLOR’S THEORY FOR MECHANISM OF CLOTTING
 ACCORDING TO BEST AND TAYLOR , FOUR SUBSTANCES,
NAMELY THROMBOPLASTIN , CALCIUM, PROTHROMBIN,
AND FIBRINOGEN ARE TAKING PART IN COAGULATION.
 THROMBOPLASTIN IS PRESENT IN THE TISSUES.
 CALCIUM OCCURES IN PLASMA
 PROTHROMBIN IS PRESENT IN THE PLASMA OF THE
CIRCULATING FLUID.
 FIBRINOGEN OCCURS IN A DISSOLVED STATE IN THE
PLASMA
 WHEN BLOOD IS SHED, THE INJURED TISSUES LIBERATE
THROMBOPLASTIN. IN THE PRESENCE OF Ca++ IONS
PROTHROMPIN IS CONVERTED INTO ACTIVE THROMBIN BY
THROMPOBLASTIN.
 THEN THROMBIN ACTS UPON SOLUBLE FIBRINOGEN,
CONVERTING IT INTO INSOLUBLE FIBRIN, WHICH IS THE
CLOT.

7. BEST AND TAYLOR’S THEORY FOR MECHANISM OF CLOTTING
PROTHROMBIN ( IN BLOOD PLASMA)
 THROMBOPLASTIN Ca++
 (FROM TISSUES AND ( IN PLASMA )
 BLOOD PLATELETS
THROMBIN (ACTIVE)
(ACT ON)
FIBRINOGEN - (SOLUBLE, PRESENT IN
PLASMA )
( CONVERTED)
FIBRIN - ( CLOT ) (INSOLUBLE)

8. 2. HOWELL’S THEORY
 ACCORDING TO HOWELL, Ca++ ALONE IS PROMOTING THE
CONVERSION OF PROTHROMBIN INTO THROMBIN.
 PRESENCE OF ANTITHROMBIN IN THE BLOOD, THE
PROTHROMBIN IS PREVENTED FROM ACTIVATION.
 WHEN THRE IS AN INJURY, THE FORMED ELEMENTS OF
THE BLOOD AT ONCE RELEAS A SUBSTANCE KNOWN AS
CEPHALIN.
 THE CEPHALIN NEUTRALISES THE ACTIVITY OF
ANTITHROMBIN AND ALLOW Ca++ TO REACT WITH
PROTHROMBIN
 THIS RESULTS IN TO FORMATION OF THROMBIN WHICH
CONVERTS FIBRINOGEN TO FIBRIN.

9. HOWELL’S THEORY FOR MECHANISM OF CLOTTING
BLOOD CORPUSCLES
CEPHALIN (substance)
NEUTRALISES
ANTITHROMBIN
 PROTHROMBIN Ca++
THROMBIN (ACTIVE)
(ACT ON)
FIBRINOGEN - (SOLUBLE, PRESENT IN
PLASMA )
( CONVERTED)
FIBRIN - ( CLOT ) (INSOLUBLE)

10. 3. FLUID AND SPIRO’S THEORY
 ACCORDING TO THIS THEORY , AN ENZYME
THROMBOKINASE PRODUCED BY THE THROMBOCYTES
(PLATLETS) , AS ESSENTIAL CONSTUENT FOR THE
COAGULATION OF BLOOD.
BLOOD PLATELETS ( THROMBOCYTES)
THROMBOKINASE (enzyme)
Ca++
PROTHROMBIN (PLASMA)
THROMBIN
(act on)
FIBRINOGEN (PLASMA)
FIBRIN

11. 4. ENZYME CASCADE HYPOTHESIS
 THIS THEORY WAS PROPOSED BY BIGGS AND MAC
FARLANE IN 1966.
 ACCORDING TO THIS HYPOTHESIS 13 FACTORS, NAMELY
FACTORS I,II,III,IV,V,VI,VII,VIII,IX,X,XI,XII AND XIII
INVOLVED IN THE COAGULATION.
 THESE FACTORS ACT AS ENZYMES AND PROENZYMES.
 THEY BRING ABOUT A SEQUENCE OF REACTION IN WHICH
EACH ENZYME ACTIVATES THE NEXT UNTIL THE CLOT
FORMED.

12. FACORS INVOLVED IN BLOOD COAGULATION
FACTORS COMMON NAME
 FACTORS I FIBRINOGEN
 FACTORS II PROTHROMBIN
 FACTORS III TISSUE THROMBOPLASTIN
 FACTORS IV CALCIUM
 FACTORS V PROACCELERIN
 FACTORS VI ACCELERIN
 FACTORS VII PROCONVERTION
 FACTORS VIII ANTIHAEMOPHILIC FACTOR
 FACTORS IX CHRISTMAS FACTOR
 FACTORS X STUART FACTOR
 FACTORS XI PLASMA THROMBOPLASTIN
ANTECEDENT
 FACTORS XII HAGMAN FACTOR
 FACTORS XIII FIBRIN STABILIZING FACTOR

13. BLOOD COAGULATION INVOLVED IN THE
FOLLOWING STEPS
 THE INJURY ALTERS FACTORS XII AND IT IS CONVERTED
INTO ACTIVATED FACTOR XII
 THE ACTIVATED FACTOR XII COVERTS FACTOR XI INTO
ACTIVATED FACTOR XI
 THE ACTIVATED FATOR XI ACTS ON FACTOR IX AND IT IS
CONVERTED INTO ACTIVATED FACTOR IX
 THE ACTIVATED FACTOR IX IN CO-OPERATION WITH
FACTOR VIII ACTS ON FACTOR X AND IS CONVERTED INTO
ACTIVATED FACTOR X
 THE ACTIVATED FACTOR X COMBINES WITH FACTOR V
AND PLATLET PHOSPHOLIPID TO FORM A COMPLEX
CALLED PROTHROMBIN ACTIVATOR.
 THE PROTHROMBIN ACTIVATOR SPLITS PROTHROMBINE
(FACTOR II ) INTO THROMBIN ( ACTIVATOR FACTOR II)
 THE THROMBIN CONVERTS FIBRINOGEN ( FACTOR I ) INTO
FIBRIN.

14. BLOOD COAGULATION INVOLVED IN THE
FOLLOWING STEPS
INJURY (injury alters factor XII)
(converts)
FACTOR XII ACTIVATED FACTOR XII
(converts)
XI A XI
(converts)
IX A IX
(converts)
X VIII A X
PLATELET PHOSPHOLIPID (form)
V
PROTHROMBIN ACTIVATOR
(splits ) (complex)
PROTHROMBIN (II) THROMBIN (A II)
(convert)
FIBRINOGEN (I) FIBRIN

15. WHY BLOOD DOES NOT CLOT IN CIRCULATION ?
 1) ENDOTHELIAL FACTORS :
 A) SMOOTHNESS OF ENDOTHELIAL LINING PREVENTS PLATELETS
 ADHESION.
 B) NEGATIVELY CHARGED PARTICLES ARE PRESENT OVER
 ENDOTHELIAL LINING WHICH REPELS THE CLOTTING FACTOR
 2) VELOCITY OF CIRCULATION ,( IF DECREASES IT LEADS TO CLOTTING )
 3) PRESENCE OF NATURAL ANTICOAGULANTS IN THE BLOOD
 ( HEPARIN,PROTEIN C)
 4) IN THE EVENT OF SPONTANEOUS CLOT FORMATION, LIVER REMOVES
 THE ACTIVATED CLOTTING FACTORS FROM THE CIRCULATION.
 5) SIMULTANEOUS ACTIVATION OF FIBRINOLYTIC SYSTEM ALONG WITH
 CLOTTING MECHANISM.
Source : Net , University books

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