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Thromb Haemost 1986; 56(01): 071-079
DOI: 10.1055/s-0038-1661606
Original Article
Schattauer GmbH Stuttgart

In Vitro Comparison of Fibrinolytic Activity of Plasminogen Activators Using a Thrombelastographic Method: In Vivo Evaluation of the B-Chain-Streptokinase Complex in the Dog Model Using Pre-Titered Doses

L Summaria
The Section of Hemostasis and Thrombosis, Department of Surgery, Evanston Hospital, and Northwestern University Medical School, Evanston, III., USA
,
J Sandesara
The Section of Hemostasis and Thrombosis, Department of Surgery, Evanston Hospital, and Northwestern University Medical School, Evanston, III., USA
,
G Yang
The Section of Hemostasis and Thrombosis, Department of Surgery, Evanston Hospital, and Northwestern University Medical School, Evanston, III., USA
,
J P Vagher
The Section of Hemostasis and Thrombosis, Department of Surgery, Evanston Hospital, and Northwestern University Medical School, Evanston, III., USA
,
J A Caprini
The Section of Hemostasis and Thrombosis, Department of Surgery, Evanston Hospital, and Northwestern University Medical School, Evanston, III., USA
› Author Affiliations
Further Information

Publication History

Received 07 January 1986

Accepted after revision 03 June 1986

Publication Date:
13 July 2018 (online)

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Summary

Thrombelastography was used to quantitatively compare the clot-lysing efficiency of 6 different plasminogen activators, using human whole blood, pooled normal plasma, and platelet rich plasma. The activators compared were the B-chain-streptokinase complex, the plasmin-streptokinase complex, the mini-plasmino-gen-streptokinase complex, tissue plasminogen activator, streptokinase, and urokinase. The most efficient activator found was the B-chain-streptokinase complex. This complex was 4.0 times more effective than streptokinase, 3.0 times more effective than the plasmin-streptokinase complex, 1.3 times more effective than the mini-plasminogen-streptokinase complex, 2.3 times more effective than tissue plasminogen activator, and 16.0 times more effective than urokinase. Although there were differences in both the coagulation and fibrinolysis thrombelastographic patterns between plasma and whole blood, the comparative efficiencies of each activator were the same with either plasma or blood

The B-chain-streptokinase complex was evaluated as a thrombolytic agent in clot-lysis experiments in the jugular vein in the dog model, using a thrombelastographic method to determine the minimum dose of activator necessary for clot-lysis. With 6 dogs infused locally with 0.25 mg (8000 I.U.) of the plasmin-streptokinase complex, the cumulative clot-lysis was 18.0 ± 3.0% with the first dose, 33.0 ± 2.1% with the second dose, and 55.2 ± 8.6% with the third dose. With 6 dogs infused locally with 0.03 mg (2000 I.U.) of the B-chain-streptokinase complex, the cumulative clot-lysis was 30.6 ± 6.4% with the first dose, 54.4 ± 9.6% with the second dose, and 80.2 ± 9.0% with the third dose.

Keywords

Plasminogen activators - Thrombelastography - Fibrinolytic parameters - B-chain-streptokinase complex - Tissue plasminogen activator
 

  • References

  • 1 Fletcher AP, Alkjaersig N, Smyrniotis FE, Sherry S. The treatment of patients suffering from early myocardial infarction with massive and prolonged streptokinase therapy. Trans Assoc Am Physicians 1958; 71: 287-296
    PubMedGoogle Scholar
  • 2 Hansen PF, Jorgensen M, Kjeldgaard NO, Ploug J. Urokinase - an activator of plasminogen from human urine. Experiences with intravenous application on twenty-two patients. Angiology 1961; 12: 367-371
    CrossrefPubMedGoogle Scholar
  • 3 Fletcher AP, Alkjaersig N, Sherry S, Genton E, Hirsh J, Bachmann F. The development of urokinase as a thrombolytic agent. Maintenance of a sustained thrombolytic state in man by its intravenous infusion. J Lab Clin Med 1965; 65: 713-731
    PubMedGoogle Scholar
  • 4 Urokinase - Streptokinase Pulmonary Embolism Trials. JAMA 1974; 229: 1606-1626
    CrossrefPubMedGoogle Scholar
  • 5 White WF, Barlow GH, Mozen MM. The isolation and characterization of plasminogen activators (Urokinase) from human urine. Biochemistry 1966; 5: 2160-2169
    CrossrefPubMedGoogle Scholar
  • 6 European Cooperative Study Group for Streptokinase Treatment in Acute Myocardial Infarction: Streptokinase in acute myocardial infarction. N Engl J Med 1979; 301: 779-785
    CrossrefPubMedGoogle Scholar
  • 7 Summaria L, Arzadon L, Bemabe P, Robbins KC. The interactions of streptokinase with human, cat, dog, and rabbit plasminogens. The fragmentation of streptokinase in the equimolar plasminogen-streptokinase complexes. J Biol Chem 1974; 249: 4760-4769
    PubMedGoogle Scholar
  • 8 Marder VJ. Guidelines for thrombolytic therapy of deep-vein thromboses. Prog Cardiovasc Dis 1979; 21: 327-332
    CrossrefPubMedGoogle Scholar
  • 9 Bell WR, Meek AG. Guidelines for the use of thrombolytic agents. N Engl J Med 1979; 30: 1266-1270
    PubMedGoogle Scholar
  • 10 Rentrop KP, Blanke H, Karsch KR et al. Acute myocardial infarction: Intracoronary application of nitroglycerine and streptokinase in combination with transluminal recanalization. Clin Cardiol 1979; 2: 354-363
    CrossrefPubMedGoogle Scholar
  • 11 Ganz W, Buchbinder N, Marcus H, Mondkar A. Intracoronary thrombolysis in evolving myocardial infarction. Am Heart J 1981; 101: 4-13
    CrossrefPubMedGoogle Scholar
  • 12 Mathey DG, Kuck KH, Tilsner V, Krebber HJ, Bleifield W. Nonsurgical coronary artery recanalization in acute transmural myocardial infarction. Circulation 1981; 63: 489-497
    CrossrefPubMedGoogle Scholar
  • 13 Markis JE, Molagold M, Parker A, Silverman KJ. Myocardial salvage after intracoronary thrombolysis with streptokinase in acute myocardial infarction. N Engl J Med 1981; 305: 77-82
    CrossrefPubMedGoogle Scholar
  • 14 Sheehan FH, Mathey DG, Schofer J, Krebber HJ, Dodge HT. Effect of interventions in salvaging left ventricular function in acute myocardial infarction: a study of intracoronary streptokinase. Am J Cardiol 1983; 52: 431-438
    CrossrefPubMedGoogle Scholar
  • 15 Bergmann SR, Lerch RA, Fox KA A et al. Temporal dependence of beneficial effects of coronary thrombolysis characterized by position tomography. Am J Med 1982; 73: 573-581
    CrossrefPubMedGoogle Scholar
  • 16 Kennedy JW, Ritchie JL, Davis KB, Fritz JK. Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1983; 309: 1477-1482
    CrossrefPubMedGoogle Scholar
  • 17 Collen D, Rijken DC, Van Damme J, Billiau A. Purification of human tissue-type plasminogen activator in centigram quantities from human melanoma cell culture fluid and its conditioning for use in vivo. Thromb Haemostas 1982; 48: 294-296
    PubMedGoogle Scholar
  • 18 Matsuo O, Rijken DC, Collen D. Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus. Nature 1981; 291: 590-598
    CrossrefPubMedGoogle Scholar
  • 19 Kominger C, Matsuo O, Suy R, Stassen JM, Collen D. Thrombolysis with human extrinsic (tissue-type) plasminogen activator in dogs with femoral vein thrombosis. J Clin Invest 1982; 69: 573-580
    CrossrefPubMedGoogle Scholar
  • 20 Collen D, Topol EJ, Tiefenbrunn AJ et al. Coronary thrombolysis with recombinant human tissue-type plasminogen activator: A prospective, randomized placebo-controlled trial. Circulation 1984; 70: 1012-1017
    CrossrefPubMedGoogle Scholar
  • 21 Van de Werf F, Ludbrook PA, Bergman SR et al. Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction. N Engl J Med 1984; 310: 609-613
    CrossrefPubMedGoogle Scholar
  • 22 Dupe RJ, English PD, Smith RA G, Green J. The activity of an acylated streptokinase-plasminogen complex (BRL 26921) in dog models of thromboses. In: Progress in Fibrinolysis. Vol. VI Davidson JF, Bachmann F, Bouvier CA, Kruithof EK O. (Eds.) Churchill Livingstone; Edinburgh - London - Melbourne - New York: 1983
  • 23 Walker JD, Davidson JF, Rae AP, Hutton I, Lawrie TD V. Acylated streptokinase-plasminogen complex in patients with acute myocardial infarction. Thromb Haemostas 1984; 51: 204-206
    PubMedGoogle Scholar
  • 24 Summaria L, Robbins KC. Isolation of a human plasmin-derived functionally active, light (B) chain capable of forming with streptokinase an equimolar light (B) chain-streptokinase complex with plasminogen activator activity. J Biol Chem 1976; 251: 5810-5813
    PubMedGoogle Scholar
  • 25 Wohl RC, Summaria L, Robbins KC. Kinetics of activation of human plasminogen by different activator species at pH 7.4 and 37° C. J Biol Chem 1980; 255: 2005-2013
    PubMedGoogle Scholar
  • 26 Wohl RC, Summaria L, Arzadon L, Robbins KC. Steady state kinetics of activation of human and bovine plasminogens by streptokinase and its equimolar complexes with various activated forms of human plasminogen. J Biol Chem 1978; 253: 1402-1407
    PubMedGoogle Scholar
  • 27 Robbins KC, Wohl RC, Summaria L. Activation of human plasminogen in both purified systems and plasma by streptokinase and urokinase activator species. In: Progress in Chemical Fibrinolyses and Thrombolyses. Vol. IV Davidson JF, Cepelak V, Samama MM, Desnoyers PC. (Eds.) 330-338 Churchill Livingstone; Edinburgh: 1979
  • 28 Summaria L, Boreisha IG, Arzadon L, Robbins KC. The dissolution of human cross-linked plasma fibrin clots by the equimolar human plasmin-derived light (B) chain-streptokinase complex. The acceleration of clot lysis by pretreatment of fibrin clots with the light (B) chain. Thromb Res 1977; 11: 377-389
    CrossrefPubMedGoogle Scholar
  • 29 Summaria L, Arzadon L, Bernabe P, Robbins KC, Barlow GH. Characterization of the amino terminal glutamic acid and the amino terminal lysine forms of human plasminogen isolated by affinity chromatography and isoelectric focusing methods. J Biol Chem 1973; 248: 2984-2991
    PubMedGoogle Scholar
  • 30 Summaria L, Robbins KC. Preparation, characterization, and stability of a sterile, equimolar, human light (B) chain-streptokinase complex suitable for clinical evaluation. Circulation 1983; 68: 111-140
    PubMedGoogle Scholar
  • 31 Summaria L, Hsieh B, Robbins KC. The specific mechanism of activation of human plasminogen to plasmin. J biol Chem 1967; 19: 4279-4283
    PubMedGoogle Scholar
  • 32 Sottrup-Jensen L, Claeys H, Zajdel M, Petersen TE, Magnusson S. Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Rowan RM, Samama M, Desnoyers PC. (Eds.). Vol 3 191-209 Raven Press; New York: 1978
  • 33 Summaria L, Robbins KC. Isolation of a human plasmin-derived functionally active, light (B) chain capable of forming with streptokinase an equimolar light (B) chain-streptokinase complex with plasminogen activator activity. J Biol Chem 1976; 251: 5810-5813
    PubMedGoogle Scholar
  • 34 Robbins KC, Summaria L, Wohl RC, Bell WR. The human plasmin-derived light (B) chain-streptokinase complex: A second-generation thrombolytic agent. Thromb Haemostas 1983; 50: 787-791
    PubMedGoogle Scholar
  • 35 Haverkate F, Traas DW. Dose-response curves in the fibrin plate assay. Fibrinolytic activity of proteases. Thromb Diathes Haemorrh 1974; 32: 356-365
    PubMedGoogle Scholar
  • 36 Vagher JP, Summaria L, Holloway SD, Caprini JA. A Laboratory manual of coagulation, platelet, and fibrinolytic assay methodology. Submitted for publication 1986
    PubMedGoogle Scholar
  • 37 Rothbard RL, Fitzpatrick PG, Caton DM, Francis CW, Hood Jr WB, Marder VJ. Relationship of systemic lytic state to acute thrombolysis with standard dose and low-dose intracoronary streptokinase (Abstr). Circulation 1983; 67 (suppl. III) (Suppl. 03) 38
    CrossrefPubMedGoogle Scholar
  • 38 Lew AS, Neer T, Rodriguez L, Geft IL, Shah PK, Ganz W. Clinical failure of streptokinase due to an unsuspected high titer of antistreptokinase antibody. JACC 1984; 1: 183-185
    PubMedGoogle Scholar
  • 39 Summaria L, Boreisha I, Barlow GH, Robbins KC. The isolation and characterization of an equimolar human light (B) chain-streptokinase-plasmino-gen complex. Circulation II 1982; 66: 11-179
    PubMedGoogle Scholar
  • 40 Summaria L, Boreisha I, Barlow GH, Robbins KC. The isolation and characterization of a ternary human plasmin light (B) chain-streptokinase-plasminogen complex. 1986 submitted for publication to Bio Bio Acta
    PubMedGoogle Scholar
  • 41 Hartert H. Die Thrombelastographie. Eine Methode zur physikalischen Analyse des Blutgerinnungsvorgangs. Z Ges Exp Med 1951; 117: 189-196
    CrossrefPubMedGoogle Scholar
  • 42 Summaria L, Sandesara J, Vagher JP, Caprini JA. Coagulation, fibrinolytic, and antithrombin-III profiles monitored in patients receiving thrombolytic therapy. 1985 (Submitted for publication.)
    PubMedGoogle Scholar
  • 43 Chmielewska J, Ranby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res 1983; 31: 427-436
    CrossrefPubMedGoogle Scholar
  • 44 Collen D. Mechanisms of inhibition of tissue-type plasminogen activator in blood. Thromb Haemostas 1983; 50: 678
    PubMedGoogle Scholar
  • 45 Korninger C, Stassen JM, Collen D. Turnover of human extrinsic (tissue-type) plasminogen activator in rabbits. Thromb Haemostas 1981; 46: 658-461
    PubMedGoogle Scholar
  • 46 Matsuo O. Turnover of tissue plasminogen activator in man. Thromb Haemostas 1982; 48: 242
    PubMedGoogle Scholar