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Heparin and AT III ..Part1..The Basics



Heparin is the most commonly used anticoagulant during operative procedures due to its cost, rapid onset, safety, and short half life as well as its reversibility.  The heparin molecule is a negatively charged molecule . 
 It's mode of action is important in understanding its limitations and potential problems that may occur with its use.  Heparin can only function after it binds to a protein that circulates naturally in the blood stream by the name of antithrombin or AT III.  
Once heparin binds to free circulating antithrombin, this complex is capable of it inhibiting thrombin as well as activated factor X.  Thrombin is the main coagulant protein in the coagulation cascade.  


AT (formerly AT III) is a glycoprotein that functions normally as a natural anticoagulant, providing inhibition of coagulation enzymes in a slow progressive manner. In the presence of heparin, AT undergoes a conformational change that results in a 1000 fold increase in inhibitory activity.  
AT has anti-inflammatory functions as well related to its effects on on the coagulation cascade,resulting in protection of the endothelial lining. 
 AT deficiency is a rare (0.16%) but serious medical condition.  These patients can see an relative risk for VTE of 7 to 8 compared to the normal population underscoring the importance of adequate AT levels.


Heparin has a few important limitations.  First, it has no inhibiting effect on FXa which is already bound to platelets in prothrombinase present at the site of a clot.  Furthermore, thrombin bound to fibrin is also excluded from the effects of the heparin-AT complex.  From a pharmakokinetic standpoint, heparin is limited in cases where large amounts of acute phase reactants are circulating in acutely ill patients as they bind heparin making it unavailable to bind to AT. This is also a problem in patients with malignancy and post partum.

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