Abstract
Antithrombin III (AT III) is the physiological inhibitor of thrombin and other serine
proteases of the clotting cascade. In the development of sepsis, septic shock and
organ failure, the plasma levels of AT III decrease considerably, suggesting the concept
of a substitution therapy with the inhibitor. A decrease of AT III plasma levels might
also be associated with other pathological disorders like trauma, burns, pancreatitis
or preclampsia. Activation of coagulation and consumption of AT III is the consequence
of a generalized inflammation called SIRS (systemic inflammatory response syndrome).
The clotting cascade is also frequently activated after organ transplantation, especially
if organs are grafted between different species (xenotransplantation). During the
past years AT III has been investigated in numerous corresponding disease models in
different animal species which will be reviewed here. The bulk of evidence suggests,
that AT III substitution reduces morbidity and mortality in the diseased animals.
While gaining more experience with AT III, the concept of substitution therapy to
maximal baseline plasma levels (100%) appears to become insufficient. Evidence from
clinical and preclinical studies now suggests to adjust the AT III plasma levels to
about 200%, i.e., doubling the normal value. During the last few years several authors
proposed that AT III might not only be an anti-thrombotic agent, but to have in addition
an anti-inflammatory effect.
Key words:
Septic shock - bacterial infection - disseminated intravascular coagulation - animal
experimentation - combination therapy
