State-of-the-Art Review : Antithrombotic Agents from Hematophagous Animals

Abstract

Bloodsucking animals produce anticoagu lantly effective substances that are a challenge to coagu lation studies. In the past 40 years efforts have been fo cused on the isolation and chemical characterization of such agents as well as on the clarification of their modes of action. Following the success in the development of the anticoagulant agent hirudin from medicinal leeches, these naturally occurring anticoagulants were recently in vestigated as a source of antithrombotics for pharmaceu tical use. These polypeptides or miniproteins were shown to be specific inhibitors of certain coagulation factors that block either the formation or the effect of thrombin or are supported by substances that inhibit the aggregation and adhesion of blood platelets and by proteolytic enzymes with fibrinolytic activity. By advances in biotechnology of protein-like substances, especially gene technology, these antithrombotics have been obtained in amounts suf ficient for preclinical and clinical studies. Thus, the in vestigation of the anticoagulant agents from hematopha gous animals offers a new line of research in antithrom botic drugs. Key Words: Bloodsucking animals— Naturally occurring anticoagulants—Fibrinolytics and platelet inhibitors.