Genetic fusion of hirudin to albumin prolongs its anticoagulant effects in vivo

Antithrombotic agents that inhibit thrombin are effective, but can cause bleeding. In order to reduce dosage requirements, we have modified the clearance behavior of hirudin, a small thrombin inhibitor polypeptide, by genetic fusion to albumin. Previously, we showed that a His-tagged hirudin fusion protein (HLAH6) derived from transfected COS cells was cleared from rabbits 160-fold slower than hirudin (Syed et al, Blood 89:3243-3252). We now …