Abstract
Antithrombin (AT) is a single-chain glycoprotein in plasma and belongs to the family
of the serpins. It is synthesized in liver parenchymal cells, and its plasma concentration
is between 112-140 mg/L. AT is a unique inhibitor of the clotting system and neutralizes
most of the enzymes generated during activation of the clotting cascade, especially
thrombin, factors Xa and IXa. Equimolar, irreversible complexes are formed between
AT and the enzymes. The interaction between AT and the activated clotting factors
is at least 1,000-fold increased in the presence of heparins. Heparins bind to multiple
sites of the AT molecule resulting in a steric reconfiguration. Heparins contain a
specific pentasaccharide unit which is the minimum requirement for AT binding. The
glycosaminoglycan (GAG) heparan sulfate found on endothelial cell surfaces also contains
this pentasaccharide and can thus “activate” AT. It is believed that much of the physiological
inactivation of enzymes by AT occurs on the endothelium, mediated by heparan sulfate.
The binding of AT to the GAGs also releases prostacyclin which possesses strong antiinflammatory
properties.
Deficiencies of AT are inherited or acquired. Only acquired defects due to increased
consumption are discussed, most notably AT in DIC, especially DIC in sepsis. During
acute DIC, clotting factors and inhibitors are consumed faster than they can be reproduced.
This consumption of AT is of great significance in DIC and sepsis, and plasma AT levels
predict outcome. AT levels drop early in sepsis and laboratory signs of DIC can already
be found in patients with SIRS and early sepsis. The important role of AT in DIC and
sepsis is the basis for considering antithrombin concentrates as an additional therapeutic
modality.
Key words:
Antithrombin - disseminated intravascular coagulation (DIC) - sepsis - anticoagulant
- antiinflammatory
