Antithrombin (AT)

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Subject: Antithrombin (AT)

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Definition

  • AT, also known as antithrombin III, is a natural inhibitor of thrombin and of other clotting factors essential in the coagulation cascade. It is synthesized in the liver. In the presence of heparin, the activity of AT is enhanced approximately 1,000 times.

  • Normal range (for functional activity): 75–125%. The functional assay can be performed in a clot detection system or in a chromogenic one. The antigen normal range is the same as for the functional assay, but the assay is rarely necessary in clinical practice.

Use

  • Because deficiency of AT may result in a thrombophilic syndrome, determination of AT is indicated in cases suspected of congenital thrombophilia. It is also of help in determining the prognosis in disseminated intravascular coagulation (DIC) because levels become markedly decreased in severe cases.

Interpretation

  • Acquired deficiencies have been reported in severe liver disease, some malignancies, use of oral contraceptives, nephrotic syndrome, and severe infections, especially if associated with DIC (the assay is useful in determining the severity of DIC: it decreases in parallel with increasing severity of the syndrome).

  • AT is not affected by deficiency in vitamin K or by vitamin K antagonists.

    • It decreases during heparin therapy.

    • Severe deficiency may result in diminished anticoagulant effect of heparin.

Limitations

  • Clotted specimen, incomplete filling of test tubes, severe lipemia, icteric samples, and hemolysis produce unreliable results.

  • Heparin therapy interferes with the coagulant assay but not with the chromogenic one.

  • AT results are affected by the use of thrombin inhibitors such as hirudin (or its congeners) or argatroban and the newer antithrombin drugs.

 
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