Download PDF
Thromb Haemost 1990; 64(03): 344-348
DOI: 10.1055/s-0038-1647315
Review Article
Schattauer GmbH Stuttgart

The Anticoagulant and Antithrombotic Properties of Hirudins

Walter E Märki
Ciba-Geigy Limited, Basle, Switzerland
,
Robert B Wallis
*   Research Centre, Ciba-Geigy Pharmaceuticals, Horsham, West Sussex, England
› Author Affiliations
Further Information

Publication History

Received 14 February 1989

Accepted after revision13 July 1990

Publication Date:
25 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints
 

  • References

  • 1 Markwardt F. The comeback of hirudin - an old established anticoagulant agent. Folia Haematol 1988; 115: 10-23
    PubMedSearch in Google Scholar
  • 2 Petersen TE, Roberts HR, Sottrup-Jensen L, Magnusson S. Primary structure of hirudin, a thrombin-specific inhibitor. In: Protides of the Biological Fluids Peters H. (ed) Pergamon; Oxford: 1976. pp 145-149
  • 3 Harvey RP, Degryse E, Stefani L, Schamber F, Cazenave JP, Courtney M, Tolstoshev’ P, Lecocq JP. Cloning and expression of cDNA coding for the anticoagulant hirudin from the bloodsucking leech Hirudo medicinalis. Proc Natl Acad Sci USA 1986; 83: 1084-1088
    CrossrefPubMedSearch in Google Scholar
  • 4 Dodt J, Machleidt W, Seemueller U, Maschler R, Fritz H. Isolation and characterization of hirudin isoinhibitors and sequence analysis of hirudin PA. Biol Chem Hoppe Seyler 1986; 367: 803-811
    CrossrefPubMedSearch in Google Scholar
  • 5 Scharf M, Engels J, Tripier D. Primary structures of new “isohirudins”. FEBS Lett 1989; 225: 105-110
    PubMedSearch in Google Scholar
  • 6 Johnson P, Sze P, Winant R, Payne P, Lazar J. Biochemistry and Genetic Engineering of Hirudin. Sem Thromb Haemostas 1989; 15: 302-315
    PubMedSearch in Google Scholar
  • 7 Meyhack B, Hinnen A, Heim J. Heterologous gene expression in Saccharomyces cerivisiae . In: Genetics and Molecular Biology of industrial Microorganisms Hershberger CL, Queener SW, Hegeman G. (ed) American Society for Microbiology; Washington, DC: 1989. pp 311-321
  • 8 Riehl-Bellon N, Carvallo D, Acker M, van Dorsselaer A, Marquet M, Loison G, Lemoine Y, Brown SW, Courtney M, Roitsch C. Purification and biochemical characterization of recombinant hirudin produced by Saccharomyces cerevisiae. Biochemistry 1989; 28: 2941-2949
    CrossrefPubMedSearch in Google Scholar
  • 9 Haruyama H, Wuethrich K. Conformation of recombinant desul-fatohirudin in aqueous solution determined by nuclear magnetic resonance. Biochemistry 1989; 28: 4301-4312
    CrossrefPubMedSearch in Google Scholar
  • 10 Wallace A, Dennis S, Hofsteenge J, Stone SR. Contribution of the N-terminal region of hirudin to its interaction with thrombin. Biochemistry 1989; 28: 10079-10084
    CrossrefPubMedSearch in Google Scholar
  • 11 Chang JY, Ngai PK, Rink H, Dennis S, Schlaeppi JM. The structural elements of hirudin which bind to the fibrinogen recognition site of thrombin are exclusively located within its acidic C-terminal tail. FEBS lett 1990; 261: 287-290
    CrossrefPubMedSearch in Google Scholar
  • 12 Krstenansky JL, Broesma RJ, Owen TJ, Payne MH, Yates MT, Mao SJ T. Development of MDL 28050, a small stable antithrombin agent based on a functional domain of the leech protein, hirudin. Thromb Haemostas 1990; 62: 208-214
    PubMedSearch in Google Scholar
  • 13 Grütter MG, Priestle JP, Rahuel J, Grossenbacher H, Bode W, Hofsteenge J, Stone SJ. Crystal structure of thrombin-hirudin complex: a novel mode of serine protease inhibition. EMBO J 1990; 9: 2361-2365
    PubMedSearch in Google Scholar
  • 14 Rydel TJ, Ravichrandran KG, Tulinsky A, Bode W, Huber R, Fenton JW, Roitsch C. The structure of a complex of recombinant hirudin and human-a-thrombin. Science 1990; 249: 277-280
    CrossrefPubMedSearch in Google Scholar
  • 15 Braun PJ, Dennis S, Hofsteenge J, Stone SR. Use of site-directed mutagenesis to investigate the basis for the specificity of hirudin. Biochemistry 1988; 27: 6517-6522
    CrossrefPubMedSearch in Google Scholar
  • 16 Fink E, Seemuller U, Dodt J, Fritz H. Proteinase inhibitors of the leech, Hirudo medicinalis. In: Haemostasis and Animal Venoms Pirkle H, Markland FS. (eds) Marcel Dekker, Inc; New York and Basel: 1988. pp 307-321
  • 17 Talbot MD. Biology of recombinant hirudin (CGP 39393): A new prospect in the treatment of thrombosis. Sem Thromb Haemostas 1989; 15: 293-301
    PubMedSearch in Google Scholar
  • 18 Johnson P, Friedberg R, Sze P, Winant R, Almquist R, Lazar J, Sung S, Hudson D. Structure function studies of the thrombin-specific inhibitor hirudin. Thromb Haemostas 1989; 62 Abs 1016
    PubMedSearch in Google Scholar
  • 19 Markwardt F. Development of hirudin as an antithrombotic agent. Sem Thromb Haemostas 1989; 15: 269-282
    PubMedSearch in Google Scholar
  • 20 Hofsteenge J, Taguchi H, Stone SR. Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors. Biochem J 1986; 237: 243-251
    CrossrefPubMedSearch in Google Scholar
  • 21 Bichler J, Fichtl B, Siebeck M, Fritz H. Pharmacokinetics and pharmacodynamics of hirudin in man after single subcutaneous and intravenous bolus administration. Arzneim Forsch 1988; 38: 704-710
    PubMedSearch in Google Scholar
  • 22 Markwardt F, Kaiser B, Novak G. Studies on antithrombotic effects of recombinant hirudin. Thromb Res 1989; 54: 377-388
    CrossrefPubMedSearch in Google Scholar
  • 23 Talbot MD, Ambler J, Butler KD, Findlay VS, Mitchell KA, Peters RF, Tweed MF, Wallis RB. Recombinant desulphatohirudin (CGP 39393): Anticoagulant and antithrombotic properties in vivo. Thromb Haemostas 1989; 61: 77-80
    PubMedSearch in Google Scholar
  • 24 Hauptmann J, Bruggener F, Markwardt F. Effect of heparin, hirudin and a synthetic thrombin inhibitor on antithrombin III in thrombin-induced disseminated intravascular coagulation in rats. Haemostasis 1987; 17: 321-328
    PubMedSearch in Google Scholar
  • 25 Ishikawa A, Hafter R, Seemüller U, Gokel JM, Graeff H. The effect of hirudin on endotoxin induced disseminated intravascular coagulation (DIC). Thromb Res 1980; 19: 351-358
    CrossrefPubMedSearch in Google Scholar
  • 26 Hoffmann A, Markwardt F. Inhibition of the thrombin-platelet reaction by hirudin. Haemostas 1984; 14: 164-169
    PubMedSearch in Google Scholar
  • 27 Markwardt F, Nowak G, Stürzebecher J, Vogel G. Clinico-phar-macological studies with recombinant hirudin. Thromb Res 1988; 52: 393-400
    CrossrefPubMedSearch in Google Scholar
  • 28 Shand RA, Smith JR, Wallis RB. Expression of the platelet procoagulant activity in vivo in thrombus formation in an extracor-poreal shunt in the rat. Thromb Res 1984; 36: 223-232
    CrossrefPubMedSearch in Google Scholar
  • 29 Butler KD, Lees CM, Mitchell KA, Peters RF, Talbot MD, Tweed MF, Wallis RB. A comparison of three experimental models of thrombosis using morphological and radiometric analysis. Thromb Haemostas 1989; 62 (Abstr) 373
    PubMedSearch in Google Scholar
  • 30 Bucha E, Nowak G, Markwardt F. Prevention of experimental coronary thrombosis by hirudin. Folia Haematol 1988; 115: 52-58
    PubMedSearch in Google Scholar
  • 31 Steele PM, Chesebro JH, Stanson AW, Holmes DR, Dewanjee MK, Badimon L, Fuster V. Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model. Circ Res 1985; 57: 105-112
    CrossrefPubMedSearch in Google Scholar
  • 32 Heras M, Chesebro JH, Penny WJ, Bailey KR, Badimon L, Fuster V. Effects of thrombin inhibition on the development of acute plate-let-thrombus deposition during angioplasty in pigs: heparin versus recombinant hirudin a direct thrombin inhibitor. Circulation 1989; 79: 657-665
    CrossrefPubMedSearch in Google Scholar
  • 33 Heras M, Chesebro JH, Webster MW I, Mruk JS, Grill DE, Penny WJ, Bowie EJ W, Badimon L, Fuster V. Hirudin, heparin and placebo during deep arterial injury in the pig: the in vivo role of thrombin in platelet mediated thrombosis. Circulation 1990 in press
    PubMedSearch in Google Scholar
  • 34 Talbot MD, Ambler J, Butler KD, Lees CM, Mitchell KA, Peters RF, Tweed MF, Wallis RB. The effects of recombinant desul-phatohirudin on arterial thrombosis in rats. Haemostasis 1990 in press
    PubMedSearch in Google Scholar
  • 35 Kaiser B, Markwardt F. Antithrombotic and haemorrhagic effects of synthetic and naturally occurring thrombin inhibitors. Thromb Res 1986; 43: 613-620
    CrossrefPubMedSearch in Google Scholar
  • 36 Markwardt F, Nowak G, Stürzebecher J, Griessbach U, Walsmann P, Vogel G. Pharmacokinetics and anticoagulant effect of hirudin in man. Thromb Haemostas 1984; 52: 160-163
    PubMedSearch in Google Scholar
  • 37 Freund M, Cazenave J-P, Courtney M, Degryse E, Roitsch C, Bernat A, Delebasee D, Defreyn G, Maffrand J-P. Inhibition by recombinant hirudins of experimental venous thrombosis and disseminated intravascular coagulation induced by tissue factor in rats. Thromb Haemostas 1990; 63: 187-193
    PubMedSearch in Google Scholar
  • 38 Markwardt F, Fink G, Kaiser B, Klöcking H-P, Nowak G, Richter M, Stürzebecher J. Pharmacological survey of recombinant hirudin. Pharmazie 1988; 43: 202-207
    PubMedSearch in Google Scholar
  • 39 Verstraete M, Hoet B, Tornai I, Stockmans F, Arnout J. Hirudin, a specific thrombin inhibitor: Pharmacokinetics and haemostatic effects in man. Circulation 1989; 80 (Abstr) 1673
    PubMedSearch in Google Scholar