This document discusses hemostasis and the mechanisms of blood coagulation. It describes that hemostasis is achieved through vascular constriction, formation of a platelet plug, formation of a blood clot through the coagulation cascade, deposition of fibrous tissue in the clot, and permanent closure of the blood vessel defect. The coagulation cascade involves the extrinsic and intrinsic pathways activating coagulation factors that ultimately convert prothrombin to thrombin and thrombin converting fibrinogen to fibrin to form a clot. Deficiencies or abnormalities in coagulation factors can cause bleeding disorders. Common coagulation tests evaluate bleeding time, clotting time, and prothrombin time.

1. HEMOSTASIS
MS.AFRIN
DEPT. OF CCT

2. HEMOSTASIS AND BLOOD
COAGULATION
• An injury causes rupture of the vessel resulting in hemorrhage. The
body mechanism try to arrest the bleeding.
• This is termed hemostasis.

3. HEMOSTASIS AND BLOOD
COAGULATION
Hemostasis is achieved by several
mechanisms:
1. vascular spasm or vasoconstriction
2. Formation of a platelet plug
3. Formation of blood clot as a result of blood
coagulation;
4. Deposition of fibrous tissue in the clot
5. Permanent closure of defect in blood
vessel

4. VASCULAR CONSTRICTION
• Whenever a blood vessel is ruptured or cut, the vessel automatically
constricts. This causes reduction of blood flow through that vessel.
Vasoconstriction is produced by nervous reflexes, local myogenic
reflexes, humoral factors released from traumatized tissues, and
blood platelets.

5. FORMATION OF PLATELET PLUG
If the damage in the blood vessel is small, it is sealed by means of a
platelet plug.

6. FORMATION OF BLOOD CLOT
• This is a powerful mechanism for hemostasis.
• In severe trauma, there is rupture of blood vessel and blood gets
exposed to exterior. Blood, when it is shed, forms a semisolid jelly-like
substance in about 15-20 s.
• Within 3-6 min, the opening in the vessel is filled with clot. After 20
min to an hour, clot retracts and completely seals the defect in the
blood vessel.

7. FORMATION OF FIBROUS TISSUE
IN THE CLOT
• After the blood clot is formed, either it is invaded by fibroblasts or it
dissolves.
• Fibroblasts are formed within few hours following clot formation. Later
in 1-2 weeks, clot is completely organized into the fibrous tissue.
• The clot dissolves by the action of special enzymes. This occurs in
places where the clot is not required and patency of the vessel has to
be maintained.

8. COAGULATION STAGES
• The substances that promote coagulation are called procoagulants.
• The inhibiting coagulation are called anticoagulants.
• In normal state, the anticoagulants pre- dominate over procoagulants and therefore
blood does not clot. But whenever the vessel ruptures, pro- coagulants in that area
become activated and over- ride the effect of anticoagulants producing the clot.
• Clotting or coagulation occurs in three basic stages:
• 1. The rupture of blood vessel results in a cascade of chemical reactions in blood
involving 12 coagulation factors. They finally form a complex of activating
substances called the prothrombin activator.
• 2. Prothrombinactivator catalyzes the conversion of the prothrombin to thrombin.
• 3. Thrombin acts as an enzyme to convert fibrinogen to fibrin.
• Fibrin forms a mesh in which the blood cells,platelets, get entangled and form a clot.

9. CLOTTING FACTORS
The formation of prothrombin activator requires 12 different coagulation factors. They
are as under. Factor I-fibrinogen: Fibrinogen is a soluble plasma protein having a
molecular weight of 3,30,000. Plasma contains about 100-700 mg/dL
It is acted upon by thrombin to form insoluble fibrin clot. Absence of factor I is termed
afibrinogenemia.
Factor II-prothrombin: Prothrombin is the inactive precursor of thrombin. It is a plasma
protein with molecular weight of 68,700. The normal concentration in plasma is 15
mg/dL. It is formed in the liver with the help of vitamin K.
Factor III-thromboplastin: This converts prothrombin to thrombin in the presence of
factors V, VII, X, Ca**, and phospholipids.
Factor IV-calcium: Ionic calcium is required for clotting. This is required for the
formation of prothrombin activator, for the conversion of prothrombin to thrombin, and
for the formation of insoluble fibrin clot.

10. CLOTTING FACTORS
• Factor V-labile factor (proaccelerin): This is required for the conversion of prothrombin to thrombin by tissue
extract and plasma factors.
• Factor VI: Absent.
• Factor VII-stable factor (proconvertin): This is required for the formation of prothrombin activator from tissue
extracts.
• Factor VIII-antihemophilic factor A: This is required for the formation of prothrombin activator by tissue
extract. Absence of this factor
• leads to disease termed hemophilia.
• Factor IX-Christmas factor (antihemophilic factor B): This is needed for the formation of prothrombin
activator from blood constituents. Lack of factor IX results in Christmas disease.
• Factor X-Stuart-Prower factor: This is also required for the formation of prothrombin activator. Absence of
this factor leads to hemorrhage.
• Factor XI-plasma thromboplastin anteced- ent (antihemophilic factor C): This is required for the formation of
prothrombin activator from blood constituents. Absence of this factor leads to hemorrhage.
• Factor XII-Hageman factor: Deficiency of this factor leads to delayed clotting This factor is activated by
glass and water-wettable surfaces. It also takes part in the formation of prothrombin activator.
• Factor XIII-fibrin-stabilizing factor: This is a plasma protein which causes polymerization of soluble fibrin to
produce insoluble fibrin.

12. CLOTTING MECHANISMS
• Clotting occurs by two pathways:
• 1. extrinsic pathway
• 2. intrinsic pathway.
• Clotting factors are necessary for the formation Of prothrombin
activator.
• Prothrombin activator is formed by two pathways.

13. EXTRINSIC PATHWAY
Trauma to the tissue releases complex tissue factors composed of
phospholipids and lipoprotein.
Tissue factor and factor VII in the presence of Ca+ ions act on factor X
to form activated factor X.
Activated factor X combines with tissuephospholipids, platelet
phospholipids, and factor V to form the complex called prothrombin
activator.

15. INTRINSIC PATHWAY
• This begins with damage to blood cells or exposure of blood to
collagen in traumatized vessel wall.
• It results in activation of factor XII to activated factor XII (XIIa).
• It also causes damage to platelets and this releases platelet
phospholipids. Activated factor XII acts on factor XI and activates it.
• Activated factor XI causes activation of factor IX.
• Activated factor IX along with activated factor VIII and traumatized
platelets cause activation of factor X.
• Activated factor X combines with factor V and platelet or tissue
phospholipids to form the complex called prothrombin activator.

17. STEPS INVOLVED IN COAGULATION
• After formation of prothrombin
activator, the second step in clotting is
the conversion of prothrombin to
thrombin
• The third step in clotting mechanism
is conversion of fibrinogen to fibrin.
• Thrombin acts on fibrinogen and
converts it to fibrin monomer by
removing four low-molecular- weight
peptides from each molecule of
fibrinogen.
• Many fibrin monomers polymerize
within seconds to form long fibrin
fiber.

18. • These fibers ultimately form a meshwork in which platelets, blood cells, and
plasma get entangled. This is known as a clot. The fibers are strengthened
by a substance known as fibrin-stabilizing factor.
• Points to remember
• Clot formation by extrinsic pathway is rapid.
• Intrinsic pathway is much slower, requiring 1-6 min to produce clotting.
Ca++ ions are absolutely necessary for both the pathways.
• Therefore in the absence of Ca++ ions clotting does not occur.
• Once a blood clot is formed, it follows one of the two courses:
• It can be invaded by fibroblasts and form fibrous tissue within about 1-2
weeks.
• It can be dissolved by substances such as plasmin or fibrinolysin.

19. APPLIED PHYSIOLOGY
• Bleeding disorders
• Hemophilia – factor VIII DEFECIENT – SEX LINKED HEREDITARY
DISEASE (MALES AFFECTED, FEMALE –CARRIERS)
• Absence of factor IX – haemophilia minor or Christmas disease
• Vitamin k deficiency –five clotting Factors (prothrombin, factor VII,IX,X
protein C) in liver . Absence or deficiency leads to defective clotting .
• Afibrinogenemia –fibrinogen defeciency (genetic defect,liver
disease,prostatic cancer)
• Thrombocytopenia – reduced number of platelets

20. COAGULATION TESTS
• Bleeding Time
• It is the time interval from the onset of bleeding to its spontaneous arrest.
• The normal bleeding time is 2-4 min. It is prolonged in thrombocytopenic
purpura.
• Clotting Time
• It is the time lag from the onset of bleeding to the appearance of first fibrin
thread.
• Normal duration is 2-8 min. It is prolonged in hemophilia.
• Prothrombin Time
• Normal prothrombin time is 11-16 s. It varies with alteration in prothrombin
level in the blood. Prothrombin time gives an indication about the total
amount of prothrombin present in the blood. Increased prothrombin time
delays coagulation. It is increased in liver diseases and vitamin K deficiency.