Hemostasis

Secondary Haemostasis

Lec 7 Dec.2015 Objectives 1.Clotting pathways 2. Anticlotting mechanisms Fibrinolysis anticoagulants

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

.

Table: system for naming blood-clotting factors.

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
Fibrin-stabilizing factor
13
XIII
High-molecular-weight kininogen
-
HMW-K
Prekalikrein
-
Pre-K
platelet phospholipid , or Platelet factor 3
-
PL , or PF3



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

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).

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


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

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)


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).

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.

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


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 coagulationcow’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.

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)

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

Tissue plasminogen activator

(T-PA)
(plasmin(active) Plasminogen (Inactive)
Lysis fibrinFigure: “Fibrinolytic System”

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.

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.

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


3. Anticoagulant for clinical use