2. • Substances which prevent coagulation of blood.
• 1) HEPARIN:
• I/V injection of heparin (0.5-1mg) postpones clotting for 3-4 hrs.
• USES OF HEPARIN:
• A) Prevent I/V blood clotting during surgery.
• B) During Dialysis.
• C) In cardiac surgery.
• D) In blood collection bags, used as anticoagulant.
3. COUMARIN DERIVATIVES
• Dicoumoral and warfarin derivatives of
coumarin.
• Used as oral antocoagulants in clinics.
• Prevent clotting by inhibiting the action of vit.K.
• Vit.K is essential for the formation of various
clotting factors namely, factor II, VII, IX and X.
4. Ethylene Diamine Tetra Acetic acid
(EDTA), Oxalate Compds and
Citrates.
• EDTA prevent clotting by removing calcium from blood (in vitro
coagulant).
• Oxalate compds. Prevent coagulation by forming calcium oxalate,
which precipitated later (they reduce blood Ca level).
• Sodium, ammonium or potassium citrate used as anticoagulant in
Lab. (in vitro).
• Citrate combines with calcium in blood to form calcium citrate and
prevent coagulation. Also used in blood banks as acid citrate
dextrose for storage purpose.
5. Prevention of Blood Clotting in the Normal
Vascular System-Intravascular Anticoagulants
• Endothelial Surface Factors:
(1) The smoothness of the endothelial cell surface.
(2) A layer of glycocalyx on the endothelium (glycocalyx
is a mucopolysaccharide adsorbed to the surfaces of the
endothelial cells), which repels clotting factors and
platelets, thereby preventing activation of clotting.
(3) A protein bound with the endothelial membrane,
thrombomodulin, which binds thrombin .
Binding of thrombin with thrombomodulin slow the
clotting process by removing thrombin , but the
thrombomodulin-thrombin complex also activates a
plasma protein, protein C, that acts as an anticoagulant
by inactivating activated Factors V and VIII.
6. (4) Antithrombin Action of Fibrin and Antithrombin III:
Among the most important anticoagulants in
the blood itself are those that remove thrombin
from the blood.
The most powerful of these are:
(1) The fibrin fibers that themselves are formed
during the process of clotting and
(2) An alpha-globulin called antithrombin III or
antithrombin-heparin cofactor.
7. 5) Protein C:
• It is activated by thrombin bound with thrombomodulin.
• Its active form acts as protease and digest factors V and
VIII and tends to inhibit clotting process.
6) Vigorous circulation of blood:
Platelets are kept away from the vessel, allows mixing of
activated clotting factors with their inhibitors.
8. (7) Heparin :
Heparin is another powerful anticoagulant.
Heparin:
Produced by the basophilic/ mast cells located in the pericapillary
connective tissue throughout the body.
When it combines with antithrombin III, the effectiveness of antithrombin III
for removing thrombin increases by a hundredfold to a thousandfold, and
thus it acts as an anticoagulant.
Therefore, in the presence of excess heparin, removal of free thrombin from
the circulating blood by antithrombin III is almost instantaneous.
The complex of heparin and antithrombin III removes several other activated
coagulation factors in addition to thrombin .
The others include activated Factors IX, X, XI, XII and thus enhancing the
effectiveness of anticoagulation.