1. Secondary Haemostasis
Lec Dec.2015
Objectives
1.Clotting pathways
2. Anticlotting mechanisms
Fibrinolysis
anticoagulants

2. 12 clotting factors was designated with
More than 50 important substances that affect blood coagulation have been found in the blood, and tissues, some that promote coagulation called procoagulants & others that inhibit coagulation called anticoagulants
12 clotting factors was designated with
Roman numerals I through XIII as shown in the .

3. prothrombin PL , or PF3 Factor Names Arabic Number Roman number
Fibrinogen 1 I
prothrombin 2 II
Tissue thromboplastin 3
III
Calcium 4 IV
Labile factor 5 V
Stable factor 7
VII
Antihemophilic factor A, classic factor, von-Willebrand factor 8
VIII
Antihemophilic factor B, Christmas factor. 9 IX
Stuart-Prower factor 10 X
Antihemophilic factor C, plasma thromboplastin 11 XI
Hageman factor, glass factor 12
XII
Table: system for naming blood-clotting factors.
Fibrin-stabilizing factor 13
XIII
High-molecular-weight kininogen -
HMW-K
Prekalikrein
Pre-K
platelet phospholipid , or Platelet factor 3
PL , or PF3

4. 1-The intrinsic pathway. 2-The extrinsic pathway. 3-The common pathway
Secondary is subdivided into three interacting pathways:
1-The intrinsic pathway.
2-The extrinsic pathway.
3-The common pathway

11. 2. Extrinsic pathway:
The name extrinsic is derived from the fact that activation of this pathway requires a factor not normally present in the blood but in the most cells of the body. This factor is known as tissue factor or tissue thromboplastin (factor III).

12. Intrinsic pathway
Is named because it begins with chemicals that are inside or intrinsic to the blood. This pathway leading to the activation of Stuart Prower factor (factor X) which in turn leads to conversion of fibrinogen (factor I) into fibrin (clot) in the common pathway. Clotting can occur in 1- 6minutes by intrinsic pathway

13. The common pathway consists of 5 different steps:
1. Activation of Stuart Prower factor by both intrinsic and extrinsic pathways. 2. Formation of prothrombin activator by activated factor X(X a). 3. Conversion of prothrombin (factor II) into thrombin by prothrombin activator. Prothrombin is a plasma protein and α-globulin, & is formed continually by the liver cells. Normal concentration in plasma is 15mg/dL. Vitamin K is required by the liver for normal formation of prothrombin. In liver disease, there is lack of vitamin K that prevents normal prothrombin synthesis can decrease the level of prothrombin in plasma & bleeding tendency results. 4. Conversion of fibrinogen into fibrin by thrombin. 5.stabilization of fibrin

14. 3.Common pathway
This is activated by both intrinsic and extrinsic pathways.
1. Activation of Stuart Prower factor by both intrinsic and extrinsic pathways.
2. Formatoin of prothrombin activator by activated factor X(X a).
3. Conversion of prothrombin
4. Conversion of fibrinogen into fibrin by thrombin.
5. Stabilization of fibrinclot)

18. The fibrin (clot) is initially a loose mesh of interlacing strands i.e. the resultant clot (fibrin) is weak & can be broken apart with ease. Activated – stabilizing factor (XIIIa) convert weak soluble fibrin into a dense, light, stable, insoluble fibrin (clot).

19. blood is drawn -----untreated glass test tube it will clot within 6-10 minutes.
drawn --- siliconized containers or into a nonwettable plastic test tube, ---1 hour.i.e does not clot. In the untreated glass test tube there is activated of factor XII (glass factor or contact factor) which initiate the intrinsic clotting mechanism.

21. Clot Retraction
Within 3-6 minutes after rupture of a blood vessel, if the vessel opening is not too large the entire opening or broken end of the vessel is filled with clot. After 20 minutes to an hour,
the clot retract----- condense into a denser

23. Role of calcium in clotting mechanism:
Clotting of blood is prevented by reducing the concentration of Ca++ either by deionizing Ca++ by reacting it with substances such as citrate ions or by precipitating the Ca++ with substances such as oxalate ion.

24. Role of Vitamin K in clotting mechanism:
. Vitamin K is fat-soluble vitamin required for synthesis of some clotting factors.
Deficiencies of vit. K can lead to severe bleeding tendencies and ineffective coagulation
cow’s milk contain more vit. K than does human milk, breast-fed infants is more susceptible to hemorrhage than bottle-fed infants. Vitamin K deficiency can result in hemorrhages such as frequent nosebleeds.

25. Anticloting mechanisms
Types of anticlotting mechanisms:
1.fibrinolysis.
2.anticoagulants
during major surgical operations and may cause clots in the brain (strokes) the lungs (embolism), the heart (infarction) and other organs (thrombosis)

26. 1. Fibrinolysis
Plasminogen which is also known as fibrinolysin is inactive form
injured tissues tissue plasminogen activator (TP-A) converts plasminogen plasmin lyses fibrin fibers

27. (Inactive) Tissue plasminogen activator (T-PA)
(plasmin(active) Plasminogen
(Inactive)
Lysis fibrin
Figure: “Fibrinolytic System”

30. 2.Anticoagulants 1. Intravascular anticoagulant
a. Antithrombin III: is a plasma protein produced by the liver & inactivates thrombin.
b. Heparin: produced by basophiles ,mast cells and endothelial cells. Activates antithrombin III which inhibits clotting. It is widely used in medical practice to prevent intravascular clotting.
c. Prostacylin: is a prostaglandin derivative produced by endothelial cells. is a vasodilator & inhibit the release of clotting factor from platelets.

31. d.Thrombodulin: produced by endothelial cells and will bind to thrombin which activates protein C which inactivates several clotting factors.
e. Plasma Ca++ in vivo, a low plasma Ca++ level enough to interfere with blood clotting.

32. 2. Anticoagulants that can be used outside the body
Heparin.
b-EDTA (ethylenediamine Tetra acetic) prevents clot formation by binding to Ca++ making them inaccessible for clotting reactions.
c-Citrate e.g. sodium citrate same action of EDTA. Citrate is not toxic to the body.
d-Oxalate ion: which precipitate Ca++ . Oxalate combines with Ca++ and form insoluble salt. Oxalate is toxic to the body.
e-Blood bank anticoagulants. Examples: a. Acid-citrate dextrose. b.citrate – phosphate dextrose

33. 3. Anticoagulant for clinical use
a. Heparin as an intravenou anticoagulant
b.Cumarins such as warfarin: prevent clot formation by suppressing the production of vit. K dependent coagulation factor II, VII, and IX & X by the liver.
Heparins and cumarins are anticoagulants used for the treatment of venous thrombosis