Download PDF
Hamostaseologie 1991; 11(03): 107-113
DOI: 10.1055/s-0038-1660289
Originalarbeiten
Schattauer GmbH

Einsatz von Hirudin zur Diagnostik von Gerinnungsvorgängen und Thrombin-induzierten Zellreaktionen

P. Walsmann
1   Institut für Pharmakologie und Toxikologie der Medizinischen Akademie Erfurt
› Author Affiliations
Further Information

Publication History

Publication Date:
26 June 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Arbeit gibt eine Übersicht über die Verfahren zum Nachweis von Hirudin und über die Verwendung von Hirudin für die Bestimmung von Thrombin und Prothrombin. Die Möglichkeit, Hirudin zur Stabilisierung von Blutkonserven und Prothrombinkonzentraten einzusetzen, wird diskutiert.

Weiterhin wird der Einfluß von Hirudin und Hirudinfragmenten auf Thrombinvermittelte Zellreaktionen beschrieben. Insgesamt unterscheidet sich rekombinantes Hirudin in seiner Inhibitoraktivität praktisch nicht von natürlichem Hirudin, während Hirudinfragmente eine modifizierte Wirkung zeigen.

 

  • LITERATUR

  • 1 Bergmann C, Dodt J, Köhler S, Fink E, Gassen HG. Chemical synthesis and expression of a gene coding for hirudin, the thrombin-specific inhibitor from the leech Hirudo medicinalis. Biol Chem HoppeSeyler 1986; 367: 731.
    PubMedGoogle Scholar
  • 2 Bichler J, Gemmerli R, Fritz H. Studies for revealing a possible sensitization to hirudin after repeated intravenous injections in baboons. Thromb Res 1991; 61: 39.
    PubMedGoogle Scholar
  • 3 Binnie CG, Erickson BW, Hermans J. Inhibitions of thrombin by synthetic hirudin peptides. FEBS-Lett 1990; 270: 85.
    CrossrefPubMedGoogle Scholar
  • 4 Bizios R, Lai LC, Cooper JA, Del Vechio PJ, Malik AB. Thrombin-induced adherence of neutrophils to cultured endothelial monolayers : increased endothelial adhesiveness. J Cell Physiol 1988; 134: 275.
    CrossrefPubMedGoogle Scholar
  • 5 Bourdon P, Maraganore JH. On the interaction of BG8865 with thrombin. Thromb Haemost 1989; 62: 533.
    PubMedGoogle Scholar
  • 6 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.
    CrossrefPubMedGoogle Scholar
  • 7 Courtney M, Loison G, Lemoine Y, RiehlBellon N, Degryse E, Brown SW, Cacenave J-P, Defreyn G, Delebasse D, Bernant A, Maffrand J-P, Roitsch C. Production and evaluation of recombinant hirudin. Semin Thromb Hemost 1989; 15: 288.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Courtney M, Loison G, Riehl-Bellon N, Tolstoshev P, Degryse E, Marquet M, Brown S, Lemoine Y, Roitsch C. The production and evaluation of recombinant hirudin. Thromb Res 1987; VII: 30.
    PubMedGoogle Scholar
  • 9 Degryse E. Determination of the specific activity of recombinant hirudin. Thromb Res 1990; 60: 433.
    CrossrefPubMedGoogle Scholar
  • 10 Degryse E, Acker M, Defreyn G, Bernat A, Maffrand JP, Roitsch C, Courtney M. Point mutations modifying the thrombin inhibition kinetics and antithrombic activity in vivo of recombinant hirudin. Protein Engineering 1989; 02: 459.
    CrossrefPubMedGoogle Scholar
  • 11 Degryse E, Ebel C. Influence of storage conditions on the activity of recombinant hirudin. Thromb Res 1991; 61: 87.
    PubMedGoogle Scholar
  • 12 DeMichele MAA, Moon DG, Fenton II JW, Minnear FL. Thrombin’s enzymatic activity increases permeability of endothelial cell monolayers. J Appl Physiol 1990; 69: 1599.
    CrossrefPubMedGoogle Scholar
  • 13 Dietl T. Proteinasen-Inhibitoren und Proteinasen des medizinischen Blutegels: Immunologie und Gewebslokalisation, Dissertation, Universität München. 1985
    PubMedGoogle Scholar
  • 14 Dodt J. Hirudine, die Thrombininhibitoren des Blutegels »Hirudo medicinalis«, Inaugural-Dissertation, Universität München. 1984
    PubMedGoogle Scholar
  • 15 Dodt J, Köhler S, Baici A. Interaction of site specific hirudin variants with alphathrombin. FEBS-Lett 1988; 229: 87.
    CrossrefPubMedGoogle Scholar
  • 16 Dodt J, Machleidt W, Seemüller U, Maschler R, Fritz H. Isolation and characterization of hirudin isoinhibitors and sequence analysis of hirudin PA. Biol Chem Hoppe-Seyler 1986; 367: 803.
    PubMedGoogle Scholar
  • 17 Dodt J, Müller HP, Seemüller U, Chang J-Y. The complete amino acid sequence of hirudin, a thrombin-specific inhibitor. FEBS-Lett 1984; 165: 180.
    CrossrefPubMedGoogle Scholar
  • 18 Dodt J, Schmitz T, Schäfer T, Bergmann C. Expression, secretion and processing of hirudin in E. coli using the alkaline phosphatase signal sequence. FEBS-Lett 1986; 202: 373.
    CrossrefPubMedGoogle Scholar
  • 19 Dodt J, Seemüller U, Maschler R, Fritz H. The complete covalent structure of hirudin. Localization of the disulfide bonds. Biol Chem Hoppe-Seyler 1985; 366: 379.
    PubMedGoogle Scholar
  • 20 Drawert J, Stein P. Untersuchungen zur Stabilisierung von Spenderblut mit Thrombininhibitoren. Folia Haematol 1986; 113: 560.
    PubMedGoogle Scholar
  • 21 Electricwala A, Sawyer R, Atkinson T. Purification and characterization of thrombin inhibitor from novel leech species. Thromb Haemost 1989; 62: 390.
    PubMedGoogle Scholar
  • 22 Fortkamp E, Rieger M, HeisterbergMoutses G, Schweizer S, Sommer R. Cloning and expression in Escherichia coli of a synthetic DNA for hirudin, the blood coagulation inhibitor in the leech. DNA 1986; 05: 511.
    CrossrefPubMedGoogle Scholar
  • 23 Freund M, Cazenave J-P, Courtney M, Degryse E, Roitsch C, Bernat A, Delebassee 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 Haemost 1990; 63: 187.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Friedberg RC, Hagen P-O, Pizzo SV. The role of endothelium in factor Xa regulation: the effect of plasma proteinase inhibitors and hirudin. Blood 1988; 71: 1321.
    PubMedGoogle Scholar
  • 25 Gilbao N, Villanueva GB, Fenton II JW. Inhibition of fibrinolytic enzymes by thrombininhibitors. Enzyme 1988; 40: 144.
    CrossrefPubMedGoogle Scholar
  • 26 Glusa E, Markwardt F. Platelet functions in recombinant hirudin-anticoagulated blood. Haemostasis 1990; 20: 112.
    PubMedGoogle Scholar
  • 27 Gray E, Watton J, Barrowcliffe TW, Thomas DP. Anticoagulant and antithrombic effects of recombinant hirudin. Thromb Haemost 1989; 62: 187.
    PubMedGoogle Scholar
  • 28 Grießbach U, Stürzebecher J, Markwardt F. Assay of hirudin in plasma using a chromogenic thrombin substrate. Thromb Res 1985; 37: 347.
    CrossrefPubMedGoogle Scholar
  • 29 Groetsch H, Damm D, Youssef RB, Haertel D. Comparison of two different methods for the determination of rDNA- hirudin in plasma samples: HPLC vs a chromogenic thrombin substrate. Thromb Res. 1991 im Druck.
    PubMedGoogle Scholar
  • 30 Grossenbacher H, Auden JAL, Bill K, Liersch M, Maerki W, Maschler R. Isolation and characterization of recombinant desulfatohirudin from yeast, a highly selective thrombin inhibitor. Thromb Res Suppl 1987; VII: 34.
    PubMedGoogle Scholar
  • 31 Haaland AK, Skjonsberg OH, Gravem K, Ryter R, Godai HC. Comparison of thrombin-antithrombin complex (TAT) levels and fibrinopeptide A following thrombin incubation of human plasma using hirudin, an inhibitor of TAT formation. Thromb Res 1991; 61: 253.
    CrossrefPubMedGoogle Scholar
  • 32 Harvey RP, Degryse E, Stefani L, Schamber F, Cazenave JP, Courtney M, Tolstoshev P, Lecocq JP. Cloning and expression of a cDNA coding for the anticoagulant hirudin from bloodsucking leech, Hirudo medicinalis. Proc Natl Acad Sci USA 1986; 83: 1084.
    CrossrefPubMedGoogle Scholar
  • 33 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.
    CrossrefPubMedGoogle Scholar
  • 34 Jackson CM, Hogg PJ. Formation of a ternary complex between thrombin fibrin II monomer and heparin influences thrombin hydrolysis of chromogenic substrates and thrombin inhibition by hirudin. Thromb Haemost 1989; 62: 42.
    PubMedGoogle Scholar
  • 35 Jakubowski JA. Inhibition of coagulation and thrombin-induced platelet activities by a synthetic dodecapeptide modeled on the carboxy-terminus of hirudin. Blood 1990; 75: 399.
    PubMedGoogle Scholar
  • 36 Jakubowski HV, Kline MD, Owen WG. The effect of bovine thrombomodulin on the specificity of bovine thrombin. J Biol Chem 1986; 261: 3876.
    PubMedGoogle Scholar
  • 37 Johnson PH, Sze P, Winant R, Payne MSPW, Lazar JB. Biochemistry and genetic engineering of hirudin. Semin Thromb Hemost 1989; 15: 288.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Jutisz M, Martinoli G, Tertrin C. Microdosage d’une activité anti-thrombique: l’hirudine. Bull Soc Chim biol 1962; 44: 461.
    PubMedGoogle Scholar
  • 39 Kisiel W, Hanahan DJ. Proteolysis of human factor II by factor Xa in the presence of hirudin. Biochem Biophys Res Commun 1974; 59: 570.
    CrossrefPubMedGoogle Scholar
  • 40 Klöcking H-P, Markwardt F. Influence of recombinant hirudin on the thrombogenicity of prothrombin complex concentrates. Pharmazie 1989; 44: 341.
    PubMedGoogle Scholar
  • 41 Klöcking H-P, Schulze-Riewald H, Markwardt F. Inhibitory effect of hirudin on thrombosis induced by prothrombin complex concentrate. Folia Haematol 1988; 115: 106.
    PubMedGoogle Scholar
  • 42 Köhler S, Dodt J. Effects of site specific amino acid exchanges in hirudin on the thrombin-hirudin interaction. Folia Haematol 1988; 115: 24.
    PubMedGoogle Scholar
  • 43 Köhler M, Heiden M, Harbauer G, Miyashita C, Möhrsdorf S, Braun B, Ernert P, Wenzel E, Rose S, Pindur G. Comparison of different prothrombin complex concentrates in vitro and in vivo studies. Thromb Res 1990; 60: 63.
    CrossrefPubMedGoogle Scholar
  • 44 Krstenansky JL, Broersma RJ, Owen TJ, Payne MH, Yates MT, Mao SJT. Development of MDL 28,050, a small stable antithrombin agent based on a functional domain of the leech protein, hirudin. Thromb Haemost 1990; 63: 208.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Krstenansky JL, Mao SJT. Antithrombin properties of C-terminus of hirudin using synthetic unsulfated Na-acetyl-hirudin45-65 . FEBS-Lett 1987; 211: 10.
    CrossrefPubMedGoogle Scholar
  • 46 Krstenansky JL, Owen TJ, Yates MT, Mao SJT. Anticoagulant peptides: Nature of the interaction of the C-terminal region of hirudin with a noncatalytic binding site on thrombin. J Med Chem 1987; 30: 1688.
    CrossrefPubMedGoogle Scholar
  • 47 Krstenansky JL, Owen TJ, Yates MT, Mao SJT. Design, synthesis and antithrombin activity for conformationally restricted analogs of peptide anticoagulants based on the C-terminal region of the leech peptide, hirudin. Biochim Biophys Acta 1988; 957: 53.
    CrossrefPubMedGoogle Scholar
  • 48 Krstenansky JL, Owen TJ, Yates MT, Mao SJT. Comparison of hirudin and hirudin PA C-terminal fragments and related analogs as antithrombin agents. Thromb Res 1988; 52: 137.
    CrossrefPubMedGoogle Scholar
  • 49 Krstenansky JL, Payne MH, Owen TJ, Yates MT, Mao SJT. C-Terminal peptide alcohol, acid and amide analogs of desulfato hirudin54-65 as antithrombin agents. Thromb Res 1989; 54: 319.
    CrossrefPubMedGoogle Scholar
  • 50 Lindhout T, Blezer R, Hemker HC. The anticoagulant mechanism of action of recombinant hirudin (CGP 39393) in plasma. Thromb Haemost 1990; 64: 464.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Loison G, Findeli A, Bernard M, NguyenJuilleret M, Marquet M, Riehl-Bellon N, Carvallo D, Guera-Santos L, Brown SW, Courtney M, Roitsch C, Lemoine Y. Expression and secretion in Scerevisiae of biologically active leech hirudin. Bio/Technology 1988; 06: 72.
    CrossrefPubMedGoogle Scholar
  • 52 Mann KG, Nesheim ME, Church WR, Haley P, Krishnawamy X. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood 1990; 76: 1.
    PubMedGoogle Scholar
  • 53 Mao SJT, Yates MT, Owen TJ, Krstenansky JL. Interaction of hirudin with thrombin. Identification of a minimal binding domain of hirudin that inhibits clotting activity. Biochemistry 1988; 27: 8170.
    CrossrefPubMedGoogle Scholar
  • 54 Mao SJT, Yates MT, Owen TJ, Krstenansky JL. Preparation of antibodies to a synthetic C terminus of hirudin and identification of an antigenic site. J Immunol Meth 1989; 120: 45.
    CrossrefPubMedGoogle Scholar
  • 55 Maraganore JM, Bourdon P, Jablonski J, Ramachandran KL, Fenton II JW. Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin. Biochemistry 1990; 29: 7095.
    CrossrefPubMedGoogle Scholar
  • 56 Maraganore JM, Chao B, Joseph ML, Jablonski J, Ramachandran KL. Anticoagulant activity of synthetic hirudin peptides. J Biol Chem 1989; 264: 8692.
    PubMedGoogle Scholar
  • 57 Markwardt F. Untersuchungen über Hirudin. Naturwissenschaften 1955; 42: 537.
    PubMedGoogle Scholar
  • 58 Markwardt F. Untersuchungen über den Mechanismus der blutgerinnungshemmenden Wirkung des Hirudins. NaunynSchmiedebergs Arch Pharmacol 1956; 229: 389.
    CrossrefPubMedGoogle Scholar
  • 59 Markwardt F. Die Isolierung und chemische Charakterisierung des Hirudins. Hoppe-Seyler’s Z physiol Chem 1957; 308: 147.
    PubMedGoogle Scholar
  • 60 Markwardt F. Die Bestimmung des Thrombins durch Titration mit Hirudin. Arch Pharm 1957; 290/60: 280.
    PubMedGoogle Scholar
  • 61 Markwardt F. Die quantitative Bestimmung des Prothrombins durch Titration mit Hirudin. Naunyn-Schmiedebergs Arch Pharmacol 1958; 232: 487.
    CrossrefPubMedGoogle Scholar
  • 62 Markwardt F. Versuche zur pharmakologischen Charakterisierung des Hirudins. Naunyn-Schmiedebergs Arch Pharmacol 1958; 234: 516.
    PubMedGoogle Scholar
  • 63 Markwardt F. Der Hirudintoleranztest. Klin Wochenschr 1959; 37: 1142.
    CrossrefPubMedGoogle Scholar
  • 64 Markwardt F, Hauptmann J, Nowak G, Kleßen C, Walsmann P. Pharmacological studies on the antithrombotic action of hirudin in experimental animals. Thromb Haemost 1982; 47: 226.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Markwardt F, Nowak G, Stürzebecher J, Grießbach U, Walsmann P, Vogel G. Pharmacokinetics and anticoagulant effect of hirudin in man. Thromb Haemost 1984; 52: 160.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Markwardt F, Nowak G, Stürzebecher U, Walsmann P. Studies on the pharmacokinetics of hirudin. Biomed Biochim Acta 1987; 46: 237.
    PubMedGoogle Scholar
  • 67 Markwardt F, Nowak G, Stürzebecher J, Vogel G. Clinico-pharmacological studies with recombinant hirudin. Thromb Res 1988; 52: 393.
    CrossrefPubMedGoogle Scholar
  • 68 Markwardt F, Stürzebecher J, Glusa E. Antithrombin effect of native and recombinant hirudins. Biomed Biochim Acta 1990; 49: 399.
    PubMedGoogle Scholar
  • 69 Markwardt F, Stürzebecher J, Walsmann P. The hirudin standard. Thromb Res 1990; 59: 395.
    CrossrefPubMedGoogle Scholar
  • 70 Markwardt F, Walsmann P. Die Reaktion zwischen Hirudin und Thrombin. HoppeSeyler’s Z physiol Chem 1958; 312: 85.
    PubMedGoogle Scholar
  • 71 Markwardt F, Walsmann P. Untersuchungen über den Mechanismus der Antithrombinwirkung des Heparins. HoppeSeyler’s Z physiol Chem 1959; 317: 64.
    PubMedGoogle Scholar
  • 72 Markwardt F, Walsmann P. Reindarstellung und Analyse des Thrombininhibitors Hirudin. Hoppe-Seyler’s Z physiol Chem 1967; 348: 1381.
    PubMedGoogle Scholar
  • 73 Markwardt F, Wenzel G. Die Anwendung der Prothrombinbestimmung mit Hirudin zur Überwachung der Behandlung mit Dicumarolderivaten. Blut 1961; 40: 796.
    PubMedGoogle Scholar
  • 74 Morin A, Arvier MM, Doutremepuich F, Vigneron C. Localization of the structural domain responsible for the chemotactic properties of thrombin on polymorphonuclear leucocytes. Thromb Res 1990; 60: 33.
    CrossrefPubMedGoogle Scholar
  • 75 Moser R, Groscurth P, Fehr J. Promotion of transendothelial neutrophil passage by human thrombin. J Cell Sci 1990; 96: 737.
    PubMedGoogle Scholar
  • 76 Ofuso FA, Fenton II JW, Choay J, Hirsh J, Buchanan MR, Blajchman MA. Activation of plasma factor V by thrombin and factor Xa: Inhibition by hirudin and synthetic pentasaccharide with high affinity to antithrombin III. Thromb Haemost 1989; 62: 33.
    PubMedGoogle Scholar
  • 77 Olson TA, Sonder SA, Wilner GD, Fenton II JW. Heparin binding in proximity to the catalytic site of human alpha-thrombin. Ann N Y Acad Sci USA 1986; 485: 96.
    CrossrefPubMedGoogle Scholar
  • 78 Owen TJ, Krstenansky JL, Yates MT, Mao SJT. N-terminal requirements of small peptide anticoagulants based on hirudin54-65 . J Med Chem 1988; 31: 1009.
    CrossrefPubMedGoogle Scholar
  • 79 Pizzo SV, Frieberg RC, Sze P, Winant R, Hudson D, Lazar JM, Johnson PH. Recombinant hirudin displaces human factor Xa from endothelial binding sites. Thromb Res 1990; 57: 803.
    CrossrefPubMedGoogle Scholar
  • 80 Prasa D, Stürzebecher J, Markwardt F. Hirudin als In-vitro-Antikoagulans. Pharmazie. 1991 im Druck.
    PubMedGoogle Scholar
  • 81 Prescott SM, Seeger AR, Zimmerman GA, McIntyre TM, Maraganore JM. Hirudin-based peptides block the inflammatory effects of thrombin on endothelial cells. J Biol Chem 1990; 265: 9614.
    PubMedGoogle Scholar
  • 82 Richter M, Walsmann P, Cyranka U, Markwardt F. 125I-Markierung von Hirudin. Pharmazie 1986; 41: 510.
    PubMedGoogle Scholar
  • 83 Richter M, Walsmann P, Markwardt F. A thrombin binding assay for 125I-hirudin. Pharmazie 1988; 43: 369.
    PubMedGoogle Scholar
  • 84 Scharf M, Engels J, Tripier D. Primary structures of new isohirudins. FEBS-Lett 1989; 255: 105.
    CrossrefPubMedGoogle Scholar
  • 85 Schlaeppi J-M, Vekemans S, Rink H, Chang J-Y. Preparation of monoclonal antibodies to hirudin and hirudin peptides. A method for studying the hirudin-thrombin interaction. Eur J Biochem 1980; 188: 463.
    PubMedGoogle Scholar
  • 86 Schmutzler R, Markwardt F. Der Hirudintest, eine Mikromethode zur Kontrolle des Prothrombinspiegels bei der Antikoagulanzientherapie. Klin Wochenschr 1962; 40: 796.
    CrossrefPubMedGoogle Scholar
  • 87 Spannagl M, Bichler J, Lill L, Schramm W, Fritz H. A fast chromogenic assay for determination of hirudin in plasma (Abstr). Thromb Haemost 1989; 62: 328.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 88 Spinner S, Stöffler G, Fink E. Quantitative enzyme-linked immunosorbent assay (ELISA) for hirudin. J Immunol Meth 1986; 87: 79.
    CrossrefPubMedGoogle Scholar
  • 89 Spinner S, Scheffauer F, Maschler R, Stöffler G. A hirudin catching ELISA for quantitating the anticoagulant in biological fluids. Thromb Res 1988; 51: 617.
    CrossrefPubMedGoogle Scholar
  • 90 Steiner V, Knecht R, Gruetter M. Isolation and purification of novel hirudins from leech Hirudinaria manillensis by high-performance liquid chromatography. J Chromatogr 1990; 530: 273.
    CrossrefPubMedGoogle Scholar
  • 91 Stölzle A. Zur perkutanen Resorption der Proteinaseninhibitoren Hirudin, Eglin und Bdellin aus dem Blutegel Hirudo medicinalis. In-vivo- und In-vitro-Studien am Meerschweinchen. Dissertation Universität München. 1982
    PubMedGoogle Scholar
  • 92 Stone SR, Hofsteenge J. Kinetics of the inhibition of thrombin by hirudin. Biochemistry 1986; 25: 4622.
    CrossrefPubMedGoogle Scholar
  • 93 Stone SR, Braun PJ, Hofsteenge J. Identification of regions of alpha-thrombin involved in its interaction with hirudin. Biochemistry 1987; 26: 4617.
    CrossrefPubMedGoogle Scholar
  • 94 Stone SR, Hofsteenge J. Effect of heparin on the interaction between thrombin and hirudin. Eur J Biochem 1987; 169: 373.
    CrossrefPubMedGoogle Scholar
  • 95 Stürzebecher J. Methods for determination of hirudin. Semin Thromb Hemost 1991; 17: 99.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 96 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 Haemost 1989; 61: 77.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 97 Talbot M. Biology of recombinant hirudin (CGP 39393). A new prospect in the treatment of thrombosis. Semin Thromb Hemost 1989; 15: 293.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 98 Tripier D. Hirudin: A family of iso-proteins, isolation and sequence determination of new hirudins. Folia Haematol 1988; 115: 30.
    PubMedGoogle Scholar
  • 99 Tuong A, Maftouh M, Picard C, Gachon H. Site specific radioiodination of recombinant hirudin. Anal Biochem 1990; 189: 186.
    CrossrefPubMedGoogle Scholar
  • 100 Walenga JM, Pifarre R, Hoppensteadt DA, Fareed J. Development of recombinant hirudin as a therapeutic anticoagulant and antithrombotic agent: some objective considerations. Semin Thromb Haemost 1989; 15: 316.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 101 Walsmann P. Hirudin as a diagnostic agent. Folia Haematol 1988; 115: 36.
    PubMedGoogle Scholar
  • 102 Walsmann P. Über den Einsatz des spezifischen Thrombininhibitors Hirudin für diagnostische und biochemische Untersuchungen. Pharmazie 1988; 43: 737.
    PubMedGoogle Scholar
  • 103 Walsmann P, Vogel G. Über die Anwendung von Hirudin in klinischen Gerinnungslaboratorien. Folia Haematol 1970; 94: 143.
    PubMedGoogle Scholar
  • 104 Walsmann P, Markwardt F. On the isolation of the thrombin inhibitor hirudin. Thromb Res 1985; 40: 563.
    CrossrefPubMedGoogle Scholar
  • 105 Weitz JI, Leslie B. Urokinase has direct catalytic activity against fibrinogen and renders it less clottable by thrombin. J Clin Invest 1990; 86: 203.
    CrossrefPubMedGoogle Scholar
  • 106 Yang X-J, Blajchman MA, Craven S, Smith LM, Anvari N, Ofosu FA. Activation of factor V during intrinsic and extrinsic coagulation. Inhibition by heparin, hirudin and D-Phe-Pro-Arg-CH2C1. Biochem J 1990; 272: 399.
    PubMedGoogle Scholar