Prevention of Blood Clotting in the Normal Vascular system

 I: Endothelial surface Factors:

      1:The smoothness of the endothelial cell surface : prevent contact activation of the intrinsic clotting

      2:Layer of glycocalyx on the endothelium it is muco- polysaccharide adsorbed to the surfaces of the

        endothelial cells repels clotting factors & platelets.

     3:Thrombomodulin remove thrombin.How?   thrombin-thrombomodulin complex activate

         protien-C which act as anti-coagulant, inactivate Va, VIIIa & increases the activity of tissue

         plasminogen activator (t-PA).

II --Anti– clotting mechanism  

   The tendency of blood to clot is balanced in vivo by limiting reactions that tend to prevent clotting inside the blood vessels and to break down any clots that do form when a vascular injury occurs.

The activated coagulation (clotting) factors must remain contained in a localized area.

 1.Coagulation automatically  initiates  fibrinolysis.    

 2. Circulating blood contain biochemical  inhibitors (anticoagulants) that  prevent coagulation & formation of fibrin.

III-Process of fibrinolysis :

Blood contains proteolytic enzymes known as the “fibrinolytic system” dissolve fibrin .The major protein of the fibrinolytic system is plasminogen  (inactive) .

When a clot is formed, the injured tissues and vascular endothelium, very slowly release a powerful activator called Tissue plasminogen activator (T-PA) that converts plasminogen into its active formplasmin → F&fibrinogen→FDP

The fibrinolytic & coagulation systems are interrelated under normal  conditions .                                  .                                                                    In rare conditions if the fibrinolytic system is activated without the activation of the coagulation system. This may result in severe bleeding problems .

If clotting mechanism is activated without activation of fibrinolytic system this may result in clotting disorders (thrombosis). 

  IV- Anticoagulants:

 Substances that prevent coagulation mechanism i.e. prevent coagulation factors from initiating clot formation. Types:

1- Intravascular anticoagulants Prevention of clotting in(NVS):-

a. Antithrombin III: is a plasma protein produced by the liver &   inactivates thrombin.85-90% of thrombin adsorb to fibrin fibers    this prevent spread of thrombin,the remaining thrombin combine with antithrombin III which block & inactivate thrombin action.

b. Heparin: produced by basophils & mast cells. Increases the effectiveness of antithrombin III about1oo to1000 folds for removing thrombin. Their combination remove activated factors XII,XI,X&IX 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 inhibits their aggregation.

d. Plasma Ca++ in vivo, a low plasma Ca++ level is enough it does not interfere with blood clotting.

2- Anticoagulants used outside the body:      

     

 a-Heparin

b-EDTA (ethylenediamine Tetra acetic acid prevents clot formation by binding to calcium making inaccessible for clotting reactions.

c-Citrate e.g. sodium citrate  have the  same

   action of EDTA .Citrate is not toxic to the body.

d-Oxalate ion: which precipitate Ca ions, Oxalate

   combine with calcium 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

 a. Heparin b. Cumarins such as warfarin

     Heparins and cumarins are anticoagulants used

    for the treatment of venous thrombosis (i.e.

    formation of clots inside blood vessels).warfarin has depressant effect on liver formation of II,VII,IX&XII

(Pathophysiology of haemostasis)

Defect in the haemostatic mechanism:

1.Bleeding disorder: lead to prolonged bleeding.

 2.Clotting disorder lead to increase clotting time

. clotting disorders: result from deficiency of any one or more of the clotting factors . For example Hemophilias.

Hemophilia A: caused by deficiency of antihaemophilic factor A (i.e. factor VIIIc). about 85% of all cases are hemophilia A.it is X-linked ,♂ have the disease &♀ are carriers .

This type of hemophilia is also called classic hemophilia It is hereditary sex - linked recessive disorder has a prevalence of 1 in 10000 persons . Those patients have

severe hemorrhagic complications in response to truma

Treatment: includes replacement therapy with factor VIII.

Hemophilia B:Occurs as a result of a deficiency of

 factor IX. It is also known as “Christmas disease” and accounts for approximately 12% of all hemophilia's. 

Hemophilia C: The least common of three major types of hemophilias, caused by deficiency of factor XI & accounts less than 3% of all hemophilia. It is inherited disease. Hemophilia C is also known as "Rosenthal syndrome.“

In all types of hemophilia bleeding usually does not occur except after trauma. Bleeding can last for weeks after extraction of a tooth. Bleeding may occur into the muscles & may result into hematomas. Bleeding in hemophilia is usually from larger vessels.            

In all types of hemophilias and Vit K deficiency OR if there is abnormality and/or deficiency of any of the clotting factors the CLOTTING TIME is PROLONGED.

While the BLEEDING TIME is NORMAL

Clotting Disorders:

Inappropriate clotting mechanisms in intact blood vessels results in fibrin clot formation, a phenomenon known as intravascular thrombosis. Thrombosis may be due to activation of clotting factors or due to lack of inhibitory factors (anticoagulants) to neutralize activated clotting factors. Once a thrombus (clot) has developed, it break away from its attachment to flow along with the blood such freely flowing clots are known as emboli.

3- Vitamin K deficiency: This is required for synthesis of clotting factors II ,VII,IX & X.

Laboratory diagnosis of bleeding disorders:

1. Bleeding time test.

2. Capillary fragility test.

 3. Platelet count.

 4. platelets functions Test.

Coagulation Screening Tests:

1. Clotting Time.

2.Thrombin Time (TT) .

3.Prothrombin Time (PT).

4.Partial Thromboplastin Time. (PTT).

5.Secreening of each of the clotting factors alone.

Coagulation tests

n  Thrombin Time(TT): Exogenous thrombin is added,intrinsic& extrinsic  pathways are bypassed so if fibrinogen is deficient TT is prolonged Normal value is 18-20 seconds.

n  Prothrombin Time (PT):Assesses the Extrinsic pathway factors because factor III is added,the intrinsic factors are bypassed.Normally PT equals 10-15 sec.

n  Partial Thromboplastin Time (PTT): Measures the competency of the intrinsic pathway Normally =35 to 45 seconds.