1. Definition : It’s stoppage of bleeding from injured blood vessel. Mechanisms of Haeomostasis : 1) Vascular spasm (Vaso constriction). 2) Platelet plug formation. 3) Blood clotting. 4) Clot retraction. 5) Repair of the injured blood vessel.

2. 1- Vascular spasm:  If the blood vessel is injured → It’s wall will contract to reduce the blood loss.  This local vasoconstriction is produced by : a)Local myogenic contraction of the wall b)Local axon reflex c)Vaso constrictor substances

3. 2-Platelet plug formation:  When a blood vessel is damaged → The endothelium is removed and the underlying collagen fibers are exposed. When platelets are exposed to collagen fibers in vascular wall → platelet plug formation occurs. a)Platelet activation b)Platelet adhesion c)Platelet aggregation  Platelet Plug passes through these stages:

4. 3-Blood coagulation:   Clots are formed by conversion of soluble fibrinogen into insoluble fibrinogen network with blood cells in its meshes.  So blood coagulation scheme can be concluded in the following four stages: 1)Formation of Prothrombin activator 2)Conversion of Prothrombin into Thrombin 3)Conversion of Fibrinogen into soluble Fibrin 4)Conversion of soluble Fibrin into insoluble Fibrin

5. This can be done by either extrinsic or intrinsic mechanisms o The clotting factors present in the blood in the inactive form.  They are 12 factors (from I to XIII) but no VI factor, clotting factors are synthesized in liver except: 1)Factor III (tissue factor). 2)Factor IV (Ca ++ ).  All the clotting factors circulate in the blood except factor III. '  Tissue factor is released from damaged tissues, they are lipoproteins in composition.  Vitamin K is essential for synthesis of factors II, VII, IX, X. Formation of prothrombin activator

6. Fibrinogen Factor I Prothrombin Factor II Thromboplastin (tissue factor). Factor III Calcium Factor IV Labile factor or proaccelerin or accelerator globulin Factor V Stable factor or pro –convention Factor VII Anti-hemophilic factor A or anti-hemophilic globulin Factor VIII Christmas factor or anti-hemophilic factor B Factor IX Stuart Prower factor Factor x Plasma thrombolastin antecedent ( Pt A) Factor xi Hageman factor or glass factor Factor XII Fibrin stabilizing factor. Factor XIII Factor XIII Clotting factors are:

7. The coagulation mechanism is responsible for conversion of soluble fibrinogen to insoluble fibrin by complex reaction (cascade reactions or theory. So, we can conclude the scheme of blood coagulation in the following four stages: Mechanism of coagulation 1)Formation of prothrombin activator. 2)Conversion of prothrombin into thrombin. 3) Conversion of fibrinogen into soluble fibrin. 4) Conversion of soluble fibrin into insoluble fibrin.

8. Intrinsic mechanismExtrinsic mechanism -All needed clotting factors are found in the blood. - i.e. it depends on the intrinsic components of blood. -It is initiated by a factor not normally found in blood. -This factor is added externally from the injured tissue. - Initiated by contact with rough surface - Initiated by injury of blood vessel. -Occurs in vivo and vitro.- Occurs in vivo only. - It is slow. (Occurs within 3-6 minutes) - It is rapid.(Occurs within 12-16 seconds). (1) Formation of prothrombin activator Stage I

9. a) Extrinsic Mechanism 1- Tissue injury leads to release of tissue thromboplastin (Factor III).. The thromboplastin is a protein-phospholipid mixture that acts as proteolytic enzyme 2- Factor VII activated Factor VII (VIla). 3- Factor X activated Factor X (Xa) 4- (Factor Xa+ Factor V + Ca+ + tissue phospholipids) = prothrombin activator. Factor V is at first inactive, then becomes activated by thrombin once clotting begins. Tissue factor VIlla & Ca++ & tissue factor

10. Extrinsic pathway of blood coagulation

11. b) Intrinsic Mechanism - Contact with rough surface as collagen fibers or glass leads to: A) Activation of factor XII (becomes Xlla) in the presence of kailikrein and high molecular weight (HMW) kininogen. b) Release of platelet phospholipids. 2- Factor XI factor factor Xla. factor Xla 3- Factor IX Xlla& HMW kininogen Factor Xla & Ca ++ 4- Factor X factor Xa 5- (Factor Xa + Factor V + Ca++ + platelet phospholipids) = prothrombin activator. Factor IXa & VIII & Ca++

12. Intrinsic pathway of blood coagulation

13. Conversion of prothrombin into thrombin - Prothrombin thrombin. ( Conversion of fibrinogen into fibrin Fibrinogen soluble fibrin Conversion of soluble fibrin into insoluble fibrin Soluble fibrin insoluble fibrin Stage II Stage III Stage IV Prothrombin activator thrombin Factor XIII & Ca ++

14. Notes on some coagulation factors Factor I (Fibrinogen) - It is the substance that clots and form Fibrin - Clotting of Fibrinogen is caused by addition of Thrombin -Fibrinogen is formed in the liver - Its normal concentration is about 300 mg % in the plasma - If it is decreased below 100 mg % it causes Hemorrhage.

15. Notes on some coagulation factors Factor II (Prothrombin) -It is a plasma protein. -Its normal concentration is about 10-20 mg % in the plasma. -It is formed in the liver in the presence of vitamin K. - Hypo-Prothrombinemia occurs secondary to deficiency of vitamin K.

16. Notes on some coagulation factors Factor III (Tissue factor) - It is lipoprotein in composition. -It is released from damaged tissues. Factor IV (Calcium) -Ionic Calcium is essential for clotting. -It is required for : a)Prothrombin activator formation b)Conversion of Prothrombin to Thrombin c)Formation of insoluble Fibrin

17. Notes on some coagulation factors Factor V (labile factor) -It is synthesized in liver. -It is required for the formation of prothrombin activator by extrinsic and intrinsic mechanisms. -Factor V is consumed during clotting therefore, it is absent from serum due to the formation of clot. Factor VII (stable factor) It is synthesized in the liver and catalyzed by vitamin K It is required for the formation of prothrombin activator by (extrinsic mechanism) It is not consumed during clotting therefore, it is present in serum as well as plasma

18. Notes on some coagulation factors Factor VIII (Anti-hemophilic factor) - It is required for the activation of Stuart factor with factor 8 and platelet phospholipids for the formation of prothrombin activator (intrinsic mechanism) - It is consumed during clotting it is therefore absent from serum. - Its deficiency leads to hemophilia A.

19. Factor IX (Christmas factor) Notes on some coagulation factors - It is also needed for prothrombin activator (intrinsic mechanism). - It is activated during clotting by active factor XI. - Its deficiency leads to chrismas disease (hemophilia B). Factor X (Stuart factor) -The activation of factor X is the common start of both extrinsic and intrinsic systems to form prothrombin activator.

20. Notes on some coagulation factors Factor XI (Plasma Thromboplastin antecedent [PTA]) -It is required for the formation of prothrombin activator because it activates factor IX (intrinsic mechanism). -Its deficiency leads to hemophilia C. Factor XII (Hageman Factor) -It is activated by its contact with: a)Collagen fiber Or b)A wettable surface such as glass -It starts the intrinsic system. -It activates factor XI.

21. Notes on some coagulation factors Factor XIII (Fibrin stabilizing factor) -It acts as an enzyme which causes polymerization of soluble fibrin to produce insoluble fibrin in the presence of calcium. N.B1. -It is a plasma globulin factor. defibrinated plasma When the clot retracts a clear non coagulable yellow fluid called serum (defibrinated plasma) is squeezed out PlasmaSerum 1.Prothrombin and fibrinogenPresentAbsent (lack) 1.Factors V and VIIIPresentAbsent (lack) 1.SerotoninLess than serumHigher than plasma

22. - reduction of Ca ions in vivo to levels that stop blood clotting is incompatible with life. this is because clotting stopd only when plasma Ca ions level is decreased to 4 mg % this level cannot be reached clinically since death would result before it is reached. N.B2 : Role of calcium ion in the intrinsic and extrinsic pathways. - Except for the first two steps in the intrinsic pathway, calcium ions are required for acceleration of all blood clotting reactions - so, in absence of Ca ions blood clotting by either pathway doesn't occur - Normal plasma calcium level is 9-11 mg %

23. Anti-coagulants -They are substances which prevent coagulation of blood. Definition: Types: -It means prevention of blood coagulation outside the body. N.B -Some snake venoms contain phosphatidase enzyme, which destroys thromboplastin. -Other venoms destroy fibrinogen. -These anti-coagulant effects of venoms act in vivo as well as in vitro.

24. 2) Collecting the blood in smooth Paraffin or silicon lined vessels → To prevent activation of F XII 3) Decalcifying agents : a) K Oxalate : precipitates Ca oxalate b) Na : combines with Ca++ to form unionized Ca compound c) Ethyl diamine tetra acetic acid: it is chelating calcium ions. -It is done by: 1) Cold : Delays clotting 4) Defibrination : Removal of the fibrin. 5) Heparin

25. Anti-coagulants -It means prevention of blood coagulation in side the body. -It’s done by: [1] Heparin (vivo and vitro) [2] Dicoumarol (vivo only)

26. Heparin -It was first extracted from liver and called heparin. It can also be extracted from other tissues eg.( lung ) It acts as anticoagulant in vivo and in vitro Origin : Site of action Structure Heparin is a mixture of mucopolysaccarides, so not given orally Route of administration It is given by intravenous or intramuscular injection. It is destroyed by heparin enzyme secreted from liver Inactivation

27. The anticoagulant dose of heparin is 10000 units given at 6 hours intervals Heparin antidote: It is electro positive substance such as Protamine sulfate which neutralize Negative charges of heparin and antagonize Its anti-cagulant action. Heparin is also used before surgury to reduce the risk of blood clots.

28. 1.Anti-coagulant in vitro and in vivo: by the following mechanisms:  Anti-prothrombin activator: prevents the activation of factor X and reduces plateletphospholipids  Anti-prothrombin:inhibits the conversion of prothrombin into thrombin  Anti-thrombin: by combination with it 2. It has a weak fibrinolytic action. 3.Heparin activates lipoprotein lipase : so it promotes clearing of blood lipaema. 4.Large doses of Heparin : Inhibit aldosterone secretion. Functions of Heparin

29. Dicoumarol  Origin:  Site of action: plant  It is plant in origin vivo  acts as an anticoagulant but only in vivo  Route of administration: oral administration  Dicoumarol is given by oral administration  Latent period &duration of action:  Dicoumarol exerts its anti-coagulant effect in vivo after a long latent period (about 2 days) and the effect remains for a long time.  Control of dose: prothrombin time.  The dose can be controlled by determination of prothrombin time.

30. HEMORRHAGIC DISORDERS Purpura Vitamin K deficincy Hemophilia

31. Purpura is a bleeding disease characterized by occurrence of spontaneous punctuates hemorrhages usually beneath the skin and petechiae (mucous membrane) and it appears as purplish spots.. Definition: Purpura Types: 1- Thrombocytopenic Purapura: That means the number of the platelets is below 50,000 mm 3 and that occurs due to: - Shortage at platelet production as a result of bone morrow damage. - Increase platelet destruction as in Hyberspleenism.

32. - Characters:

33. Vitamin K deficiency Causes

34. Sex-linked inherited bleeding disease Transmitted by females to the male infant. The females don't usually suffer from Hemophilia. Transmitted by females to the male infants. The injured vessel causes severe hemorrhage for long time. Coagulation time ↑ is prolonged. Bleeding time is not affected. Hemophilia Characters

35. Types :