Mechanism of blood coagulation Conversion of prothrombin to thrombinConversion of prothrombin to thrombin:

•After prothrombin activator has been formed, it cause conversion of prothrombin to thrombin in the presence of calcium ions.

The rate of thrombin formation is directly proportional to quantity of prothrombin activator ,which in turn proportional to the degree of the trauma to the vessel wall

So the rapidity of the clotting process is proportional to the quantity of thrombin formed.

Conversion of fibrinogen into fibrinConversion of fibrinogen into fibrin;;Thrombin acts on fibrinogen to remove two low molecular weight from each molecule of fibrinogen forming a molecule of fibrin monomer.

Then fibrin monomer polymerized to other monomer to form loose fibrin threads .

Within few minutes covalent cross-linkages between adjacent fibrin threads occur which convert them into dense tight aggregate.

The reaction is catalyzed by activated factor 13, fibrin stabilizing factor and in the presence of calcium

• The blood clot • The clot is composed of a meshwork of fibrin

threads running in all directions and entrapping blood cells ,platelets and plasma ,the fibrin threads adhere to damaged surface of the blood vessels .

• Clot retrction ; withen few minutes after a clot is formed it begins to contrat and expresses a fluid called serum

• Lysis of the blood clots• Once blood clot has been formed it has two

separate ways• 1- It can be invaded by fibroblast which

subsequent formed connective tissues.• Or it can be dissolutes.

Prevention of blood coagulation• Endothelial surface factor:Endothelial surface factor:1-Smothness of the endothelium: Which prevent contact activation of the clotting system.2- Monomolecular layer of negatively charged protein it repels clotting factor and platelets

of When the inner surface of the endothelial is damaged it activates the intrinsic pathway clotting.

• Anti thrombin factorsAnti thrombin factorsThere are two substances that remove thrombin from the blood .they are ;• The fibrin threads about 85-90% of thrombin become adsorbed to the fibrin

threads ,this helps to prevent the spreads of the thrombin• Anti thrombin heparin cofactorAnti thrombin heparin cofactor The thrombin that does not adsorb to fibrin threads combines with this factor, this

inactivate thrombin and block its effects on fibrinogen

• HeparinHeparin• Normally present in the blood formed by mast cells in the connective tissues &

basophile cells of the blood • Heparin prevents blood coagulation both in vivo & in vitro.• Inhibit the action of thrombin on fibrinogen• Prevent the activation of prothrombin.

• Alpha 2 macroglobulin:Alpha 2 macroglobulin:•It is similar to antithrombin heparin cofactor.

Prevention of blood coagulation outside the body:• 1- precipitation of ca+ ions in the blood by addition of oxalates• 2-Deionization of ca+ by addition of citrate• 3- Collection of a blood in silicone container which prevent contact activation of F XII • 4-Addition of heparin

Prevention of blood coagulation inside the body in vivo)

• HeparinHeparinOrigin : formed by mast cells & basophile.Mode of action:

Antiprothrombin ,antithrombin .prevent activation of f IXSite of action: both in vivo& in vitro

Dicumarol:Dicumarol:Origin; plant.Mode of action:

Compitive inhibition of vit K in the liver, so it inhibit formation of prothrombin & factor V,IX ,X.

Site of action:Only in vivo

Hemorrhagic disorders

Thrombocytopenia )thrombocytopenia purpura)This is a disease characterized by a very low level of platelets is below 50.ooo/cubic mm

There is a tendency of spontaneous bleeding from small capillaries under the skin and mucous membranes and in the internal organ.

Types I- idiopathic thrombocytopenia:I- idiopathic thrombocytopenia: the cause is unknown.

II- Secondary thrombocytopeniaII- Secondary thrombocytopenia: Due to aplasia in the bone marrow, fever ,drug sensitivity..

In purpura the coagulation time is normal but the bleeding time is prolonged.

ThrombastheniaThrombastheniaThis is a state in which the platelets are normal in numbers, but defective in function ,it is

common in sever uremia and exposure of certain drugs as aspirin.

• Hemorrhagic disorders due to defect in clotting mechanism

• Hemophilia;It is inherited sex-linked disease transmitted by females to males ,but females themselves show no

symptoms..The coagulation time is prolonged which may take from 1-12 hours ,while the bleeding time is normal A slight injury cause sever hemorrhage which may continue for several hours.

• Thre are three types of hemophilia

• Hemophilia AHemophilia A )85%) due to lack of factor VII

• Hemophilia BHemophilia B )10%)due to lack of factor IX

• Hemophilia CHemophilia C )5%) due to lack of factor XI• In hemophilia the intrinsic pathway is defective

• VITAMIN K Deficiency:• Prothrombin and factor VII,IX,X required vitamin k for synthesis by the liver,therefore in

absence of vit k ,formation of these factor are decreased • Causes of vit K DeficiencyCauses of vit K Deficiency ; ;• I-Sterility of the intestine )no bacteria)these common in newly born infants and on prolonged

ueses of antibiotics • II- failure of absorption of vit K ,as in obstructive jaundice due to absence of bile salts ,fatty

diarhea,liver diseases .in vitamin k deficiency both extrinsic & intrinsic pathways are defective