Anticoagulant protein extracted from the salivary glands of the medicinal leech, Hirudo medicinalis Linn. Hirudin is a single chain polypeptide containing 65 amino acids; mol wt approximately 7000 daltons. Several isoforms have been identified. A specific inhibitor of thrombin, q.v., hirudin does not require the presence of other coagulation factors. Isoln: J. B. Haycraft, Arch. Exp. Pathol. Pharmakol. 18, 209 (1884). Initial characterization: F. Markwardt, Naturwissenschaften 42, 537 (1955). Improved isoln: P. Walsmann, F. Markwardt, Thromb. Res. 40, 563 (1985). Amino acid sequence: T. E. Petersen et al. in Protides of the Biological Fluids vol. 23, H. Peeters, Ed. (Pergamon Press, London, 1976) pp 145-149. Antithrombin activity: F. Markwardt, Methods Enzymol. 19, 924 (1970). Pharmacokinetics in humans: F. Markwardt et al., Thromb. Haemostasis 52, 160 (1984). Chromogenic assay in plasma: U. Griessbach et al., Thromb. Res. 37, 347 (1985). Series of articles on development, pharmacology, and therapeutic potential of natural and recombinant hirudins: Semin. Thromb. Hemostasis 15, 261-333 (1989). Review of pharmacology and therapeutic potential: P. H. Johnson, Annu. Rev. Med. 45, 165-177 (1994); of therapeutic use in myocardial infarction: U. Zeymer, K.-L. Neuhaus, Drug Saf. 12, 234-239 (1995).
Identical in amino acid sequence to natural hirudin variant 1 (HV1) except that it lacks a sulfate group on Tyr at residue 63. Production by recombinant DNA technology: M. Liersch et al., EP 168342 (1986 to Ciba-Geigy); eidem, US 5422249 (1995 to Ciba-Geigy; UCP Gen-Pharma); E. Fortkamp et al., DNA 5, 511 (1986); J. Dodt et al., FEBS Lett. 202, 373 (1986). Physicochemical properties: A. Electricwala et al., Thromb. Haemostasis 63, 499 (1990). Clinical pharmacology: M. Verstraete et al., J. Am. Coll. Cardiol. 22, 1080 (1993). Clinical trial in coronary angioplasty: A. A. van den Bos et al., Circulation 88, 2058 (1993); in acute coronary syndromes: E. J. Topol et al., N. Engl. J. Med. 335, 775 (1996).
Peptide of 65 amino acids produced by recombinant DNA technology. Prepn: P. Crause et al., EP 324712; eidem, US 5180668 (1989, 1993 both to Hoechst AG). Clinical pharmacology: H. J. Roethig et al., Int. Congr. Ser. 944, 227 (1991). Clinical trial as adjunctive therapy with TPA: U. Zeymer et al., Am. J. Cardiol. 76, 997 (1995); in heparin-induced thrombocytopenia: F. Schiele et al., Am. J. Hematol. 50, 20 (1995).
Antithrombotic.
Anticoagulant