Rx: Antithrombin 3 deficiency



AT3 is known to slowly break up fibrin and factor X. When heparin binds to AT3, AT3 will break up fibrin and factor X faster. AT3 is not dependent on vitamin K so unlike warfarin, giving vitamin K will not reverse the effects of heparin.

A.  Types

    1. Type I antithrombin deficiency


    1. complete loss of the mutant antithrombin protein result in immunologic and functional levels that are 50% or less than normal.


    1. major gene deletions or point mutations, which cause a quantitative reduction in antithrombin


    1. Homozygous type I antithrombin deficiency (AT deficiency) is almost always fatal in utero.


B.  Type II antithrombin deficiency

    1. single amino acid changes that result in functional deficits in a molecule that is otherwise synthesized and secreted into the plasma in a normal fashion.


    1. The variant antithrombin molecules may have abnormalities at the reactive site or the heparin binding site.


    1. Heterozygous


C.  Acquired

    1. Liver or renal failure


    1. Pregnancy


    1. Bone marrow tumor


    1. Ards


    1. Sepsis



    • Gene assay


    • Looking for underlying cause in acquired cases



D.  Medical Care

    • pt w/ inherited AT deficiency:


    • intravenous heparin


    • if iv heparin doesn’t work , antithrombin concentrate


    • LMWHs also require antithrombin for their antithrombotic action. Not much is known about the use of LMWHs in these patients.


    • synthetic anti–factor Xa pentasaccharide


2.  pts w/ DVT and whose antithrombin deficiency has been recognized : lifelong oral anticoagulation therapy

    • synthetic direct thrombin inhibitors that do not require antithrombin for their anticoagulant effect (eg, argatroban)


3. Antithrombin supplementation has been suggested to be useful in patients with the following conditions or those undergoing the following procedures:

a.  Malignancies b.  Sepsis c.  Shock d.  Open heart surgery d.  Orthopedic procedures

E.  Surgical Care

Replacement with antithrombin concentrate is necessary in patients with known antithrombin deficiency (AT deficiency). In patients with acute severe trauma, some studies suggest a beneficial effect with prophylactic replacement. The frequency of antithrombin replacement depends on the half-life of the product, but in the presence of active bleeding, more frequent replacement should be based on antithrombin levels.

In acquired disorders, correction of antithrombin levels allows heparin to exert its full antithrombotic effect. Such replacement is necessary to maintain a minimum of 80% antithrombin activity until the full therapeutic effect of oral anticoagulants is obtained. Serial assessment of antithrombin levels is necessary to assure the adequacy of the dosing.

Aprotinin ,a third antifibrinolytic drug obtained from bovine lung, is a nonhuman protein inhibitor of several serine proteases, including plasmin. It is approved by the FDA for use in patients undergoing open heart surgery to reduce operative blood loss



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