Biochem/physiol Actions

The anticoagulant, hirudin, is the most potent natural inhibitor of both soluble and clot-bound thrombin. It binds thrombin with high affinity, covering more than 20% of its surface area and occluding both the active site and exosite I (fibrinogen and PAR recognition site). Hirudin blocks thrombus growth and platelet activation. It is not metabolized in the bloodstream of humans and is eliminated unchanged via kidney filtration.

Recombinant hirudin appears to be antigenic. Independent studies have found that 50-70% of patients treated for several days with recombinant hirudin develop at least one hirudin antibody isotype. The antibodies reduce the anticoagulant effect of hirudin, but prolong its plasma half-life by reducing renal filtration.

Unit Definition

1 U corresponds to 1 ATU (antithrombin unit; 1 ATU is defined as the amount of inhibitor that neutralizes 1 NIH unit of thrombin).