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Antithrombin: its physiological importance and role in DIC

E F Mammen1

  • 1Department of ObGyn, Wayne State University School of Medicine, Detroit, Michigan, USA.

Seminars in Thrombosis and Hemostasis
|March 27, 1998
PubMed
Summary

Antithrombin (AT) is a vital plasma protein that inhibits blood clotting. Low AT levels in sepsis and disseminated intravascular coagulation (DIC) indicate poor outcomes and may warrant AT concentrate therapy.

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Area of Science:

  • Biochemistry
  • Hematology
  • Molecular Biology

Background:

  • Antithrombin (AT) is a plasma serpin synthesized in the liver, crucial for regulating the clotting cascade.
  • AT neutralizes key clotting enzymes like thrombin and factor Xa, forming irreversible complexes.
  • Heparins and endothelial heparan sulfate significantly enhance AT's inhibitory activity through specific pentasaccharide binding.

Purpose of the Study:

  • To elucidate the role of Antithrombin (AT) in the clotting system and its clinical significance.
  • To investigate the mechanism of AT activation by heparins and heparan sulfate.
  • To examine the implications of AT consumption in Disseminated Intravascular Coagulation (DIC), particularly in sepsis.

Main Methods:

  • Review of biochemical interactions between AT, clotting factors, and glycosaminoglycans (GAGs).

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  • Analysis of AT's role in physiological anticoagulation and its interaction with heparin.
  • Examination of clinical data correlating AT levels with outcomes in DIC and sepsis.

    • Main Results:

    • AT forms equimolar complexes with activated clotting factors, with activity dramatically increased by heparins.
    • Heparan sulfate on endothelial cells activates AT, contributing to physiological anticoagulation and releasing anti-inflammatory prostacyclin.
    • Decreased AT levels are observed early in sepsis and DIC, correlating with disease severity and predicting patient outcomes.

    Conclusions:

    • AT is a critical inhibitor of coagulation, with its activity modulated by GAGs.
    • Acquired AT deficiency due to consumption is significant in DIC and sepsis.
    • Monitoring AT levels is important in sepsis and DIC, and AT concentrates are a potential therapeutic option.