How could the bleeding from an injured vessel stop spontaneously?

1-Describe the mechanism of normal haemostasis.

І. Primary Hemostasis: There is a sequence of events which occurs at the site of vascular injury, in the form of interaction between platelets and the vessel wall.

A-Blood vessel wall is injured.

B-Circulating blood is exposed to the subendothelium.

C-Platelets adhere to the injured area.

Adherence between platelets and collagen is mediated by Von Willebrand's Factor (VWF).

1-Mediator of platelet adhesion to subendothelial collagen.

2-Large protein that is a carrier of Factor VIII.

3-Binds to subendothelial collagen and platelet receptors, initiating adhesion.

D-The adherent platelet then undergo aggregation, forming the temporary primary hemostatic plug which is short-lived (seconds to minutes).

E-Platelets contain a large number of procoagulants and clotting factors providing an optimum environment for activating the coagulation cascade (secondary hemostasis).

II. Secondary Hemostasis: Describes the formation of fibrin through the activation of clotting factors (the coagulation cascade is the model generally used to describe the mechanism of coagulation).

The cascade is separated into three parts:

A. Intrinsic pathways:

• Factors involved: XII, XI, IX, and VIII.
• Activated when circulating Factor XII comes in contact with and is bound to a negatively charged surface. This causes a change in the molecular configuration of Factor XII and together with HMWK and prekallikrein it becomes an active enzyme, XII_a. This activated enzyme is then able to cause a similar change in Factor XI. After activation, Factor XI_a, in a calcium dependent reaction, converts Factor IX to its active form, Factor IX_a. A phospholipid surface is also needed for Factor IX_a conversion and is provided by activated platelets, as Platelet Factor Three (PF3). Factor IX can also be activated by the tissue factor, Factor VII complex; the initiating complex of the extrinsic pathway. Factor X can be activated to Factor X_a by either the Factor VII_a complex or by the complex of Factor IX_a and Factor VIII. Factor X_a in the presence of Factor V, calcium and phospholipid surface converts Factor II (prothrombin) to Factor II_a (thrombin) which converts Factor I (fibrinogen) to fibrin
• commonly measured by the aPTT test,

B. Extrinsic pathways

• Factors involved: VII, factor III.
• The extrinsic pathway is initiated by the

1- Release of tissue thromboplastin (Factor III) which is exposed to the blood from damaged blood vessel. Factor VII forms a complex with tissue thromboplastin and calcium.

2- This complex converts Factor X to the enzyme form Factor X_a.

3- Factor X_a catalyzes the prothrombin (Factor II) to thrombin (Factor II_a) thrombin converts fibrinogen (Factor I) to fibrin.

• commonly measured by the PT test

C. Common pathways:

• activation from the intrinsic and/or the extrinsic pathway
• Once factor X is initiated, the common pathway of coagulation is initiated and insoluble fibrin is generated, causes a long-lasting (minutes to hours) secondary plug to form.
• The plug allows normal blood flow through the affected area and repair of the damaged blood vessel.

III. Fibrinolysis: means lysis of a clot or thrombus through the activation of plasminogen into plasmin.

• The role of the fibrinolytic system is to destroy or lyse fibrin clots or thrombi.
• Plasminogen (proenzyme) is activated into plasmin by factor XIIa or other tissue activators.
• Plasmin degrades fibrinogen and fibrin into fibrin degradation products (FDP's) which can be measured. FDP's inhibit platelets, contributing to petechiae and ecchymoses in patients with DIC.
• Biodegrades factors V, VIII, IX and XI.

A. Enhanced fibrinolysis typically results in spontaneous bleeding.

B.The fibrinolytic system has built-in inhibitory mechanisms to control fibrinolysis.

IV. Natural Anticoagulants: prevent massive thrombus formation when Coagulation is initiated ie they oppose the effects of the components of the coagulation cascade.

Maintain the balance between clotting and bleeding.

• The most important inhibitors of Hemostasis (Anticoagulants):

1. Antithrombin III is the most important inhibitor of the coagulation enzymes. AT-III binds to activated factors rendering them inactive (XII_a, XI_a, X_a, IX_aand thrombin)

2. Protein C:

• Vitamin K dependent
• Is an inhibitor of the activated Factors Va and VIIIa.
  This is its anticoagulant function. Protein C also inactivates tissue plasminogen activator inhibitor (PAI) which increases the activity of tissue plasminogen activator (tPA) which enhances fibrinolytic activity. Therefore, it can be said that Protein C has both anticoagulant and fibrinolytic functions

3. Protein S :

• Vitamin K dependent

• Protein C co-factor

• Inhibits Factors V and VIII

 

Next lesson will help you to classify the causes of bleeding tendancy.