Hirudin

Abstract

For centuries, the blood-sucking medicinal leech, Hirudo medicinalis, has been used in European medicine to treat a steadily increasing number of diseases. In the 19th century, leech therapy was the most frequently chosen treatment modality, which almost led to the eradication of this animal. Prolonged bleeding from skin lesions produced by leeches was well-known and regarded as part of the therapeutic success. However, it was not until the late 19th century when Haycraft discovered the pharmacologic principle in the secretion of leeches: it inhibits blood coagulation. Decades of intensive research beginning in the 1950s led to detailed characterization of the active substance being produced by the parapharyngeal glands of Hirudo medicinalis: native hirudin, the most potent, natural direct thrombin inhibitor known. Despite constituting an anticoagulant with remarkable potency, however, its limited available amount hindered introduction of purified hirudin into clinical medicine. When the progress in recombinant technology allowed large-scale production of recombinant hirudins (r-hirudins) without markedly diminishing its antithrombin efficacy as compared to their native counterpart, preclinical and clinical trials with r-hirudins were performed. Clinical trials addressing treatment of heparin-induced thrombocytopenia, deep-vein thrombosis, and acute coronary syndromes gave important insights into efficacy and safety of r-hirudin anticoagulation. In 1997, two r-hirudins were approved by the European Agency for the Evaluation of Medicinal Products (EMEA): lepirudin for the treatment of heparin-induced thrombocytopenia (HIT) and thromboembolic disease, and desirudin for the treatment of deep-vein thrombosis in elective hip and knee surgery. FDA approval of lepirudin for the treatment of HIT and thromboembolic disease followed in 1998.