What are the different types of hereditary antithrombin (AT) deficiency?

By William Aird

  • Type I
    • Quantitative deficiency – functional activity and antigenic levels AT are proportionately reduced.
    • Most commonly caused by short deletions and insertions and less commonly by single base pair substitutions.
    • The deletions vary from 1 to 30 base pairs in length and are scattered throughout the AT gene.
  • Type II
    • Qualitative deficiency – normal antigen levels are found in association with low AT activity due to a dysfunctional protein.
    • Commonly arise secondary to single base pair substitutions.
    • Much more common than type I.
  • Three subtypes
      • Type IIa – caused by mutations that affect AT’s reactive site (i.e. the region where AT binds to its target protease).
      • Type IIb
        • An abnormality of the heparin-binding domain of AT, interfering with AT activity only in the presence of heparin.
        • Significantly lower risk for thrombosis than individuals with other types of AT deficiency.
      • Type IIC – pleiotropic group of mutations near the reactive loop site, which may interfere with the mobility of the reactive loop site after heparin binding, thus influencing AT’s interaction with thrombin.