PDF herunterladen
Thromb Haemost 1993; 70(06): 0998-1004
DOI: 10.1055/s-0038-1649714
Original Article
Fibrinolysis
Schattauer GmbH Stuttgart

Plasminogen Depletion during Streptokinase Treatment or Two-Chain Urokinase Incubation Correlates with Decreased Clot Lysability Ex Vivo and In Vitro

Páll T Önundarson
1   The Department of Hematology, Landspítalinn University Hospital, Reykjavik, Iceland
,
H Magnús Haraldsson
1   The Department of Hematology, Landspítalinn University Hospital, Reykjavik, Iceland
,
Lena Bergmann
1   The Department of Hematology, Landspítalinn University Hospital, Reykjavik, Iceland
,
Charles W Francis
2   The Hematology Unit, Department of Medicine, University of Rochester, School of Medicine and Dentistry, Rochester, New York, USA
,
Victor J Marder
2   The Hematology Unit, Department of Medicine, University of Rochester, School of Medicine and Dentistry, Rochester, New York, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 28. April 1993

Accepted after revision 01. Juli 1993

Publikationsdatum:
06. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

The relationship between lytic state variables and ex vivo clot lysability was investigated in blood drawn from patients during streptokinase administration for acute myocardial infarction. A lytic state was already evident after 5 min of treatment and after 20 min the plasminogen concentration had decreased to 24%, antiplasmin to 7% and fibrinogen 0.2 g/1. Lysis of radiolabeled retracted clots in the patient plasmas decreased from 37 ± 8% after 5 min to 21 ± 8% at 10 min and was significantly lower (8 ± 9%, p <0.005) in samples drawn at 20, 40 and 80 min. Clot lysability correlated positively with the plasminogen concentration (r = 0.78, p = 0.003), but not with plasmin activity. Suspension of radiolabeled clots in normal plasma pre-exposed to 250 U/ml two-chain urokinase for varying time to induce an in vitro lytic state was also associated with decreasing clot lysability in direct proportion with the duration of prior plasma exposure to urokinase. The decreased lysability correlated with the time-dependent reduction in plasminogen concentration (r = 0.88, p <0.0005). Thus, clot lysability decreases in conjunction with the development of the lytic state and the associated plasminogen depletion. The lytic state may therefore limit reperfusion during thrombolytic treatment.

 

  • References

  • 1 Marder VJ, Sherry S. Thrombolytic Therapy: Current Status. New Engl J Med 1988; 318 1512–20 and 1585-1595
    CrossrefPubMedGoogle Scholar
  • 2 Bovill E, Triplett D, Stump D. Role of the clinical laboratory in monitoring fibrinolytic therapy of acute myocardial infarction. Hematol Pathol 1990; 4: 1-6
    PubMedGoogle Scholar
  • 3 Brügeman J, van der Meer J, Takens BH, Hillege H, Lie KL. A systemic non-Iytic state and local thrombolytic failure of anistreplase (anisoylated plasminogen streptokinase activator complex, APS AC) in acute myocardial infarction. Br Heart J 1990; 64: 355-358
    CrossrefPubMedGoogle Scholar
  • 4 Rothbard RL, Fitzpatrick PG, Francis CW, Caton DM, Hood WB, Marder VJ. Relationship of the lytic state to successful reperfusion with standard- and low-dose intracoronary streptokinase. Circulation 1985; 71: 562-570
    CrossrefPubMedGoogle Scholar
  • 5 Burket MW, Smith MR, Walsh TE, Brewster PS, Fraker TD. Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state. Am J Cardiol 1985; 56: 441-444
    CrossrefPubMedGoogle Scholar
  • 6 Marder VJ. Comparison of thrombolytic agents: Selected hematologic, vascular and clinical events. Am J Cardiol 1989; 64: 2A-7A
    CrossrefPubMedGoogle Scholar
  • 7 Rapoport E. Thrombolysis, anticoagulation, and reocclusion. Am J Cardiol 1991; 67: 17E-22E
    PubMedGoogle Scholar
  • 8 GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo studio della soprav-vivenza nell’infarto miocardico. Lancet 1990; 336: 65-71
    PubMedGoogle Scholar
  • 9 ISIS-3 (Third international study of infarct survival) collaborative group. ISIS-3: a randomised comparison on streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute myocardial infarction. Lancet 1992; 339: 753-770
    CrossrefPubMedGoogle Scholar
  • 10 Collen D. Coronary thrombolysis: Streptokinase or recombinant tissue-type plasminogen activator?. Ann Int Med 1990; 112: 529-538
    CrossrefPubMedGoogle Scholar
  • 11 Matsuo O, Rijken DC, Collen D. Comparison of the relative fibrinogenolytic, fibrinolytic and thrombolytic properties of tissue plasminogen activator and urokinase in vitro. Thromb Haemost 1981; 45: 225-229
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 12 Önundarson PT, Francis CW, Marder VJ. Depletion of plasminogen in vitro or during thrombolytic therapy limits fibrinolytic potential. J Lab Clin Med 1992; 120: 120-128
    PubMedGoogle Scholar
  • 13 Whitaker AN, Rowe EA, Masci PP, Joe F, Gaffney PJ. The binding of glu- and lys-plasminogens to fibrin and their subsequent effects of fibrinolysis. Thromb Res 1980; 19: 381-391
    CrossrefPubMedGoogle Scholar
  • 14 Iga Y, Stella SR, Chandler AB. Kinetics of urokinase-induced thrombolysis in a biphasic in vitro system. Haemost 1985; 15: 189-197
    CrossrefPubMedGoogle Scholar
  • 15 Sabovic M, Lijnen HR, Keber D, Collen D. Correlation between progressive absorbtion of plasminogen to blood clots and their sensitivity to lysis. Thromb Haemost 1990; 64: 450-454
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Nishino N, Kakkar W, Scully MF. Influence of intrinsic and extrinsic plasminogen upon the lysis of thrombi in vitro. Thromb Haemost 1991; 66: 672-677
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 17 Watahiki Y, Scully MF, Ellis V, Kakkar VV. Potentiation by lys-plasminogen of clot lysis by single or two chain urokinase-type plasminogen activator or tissue-type plasminogen activator. Thromb Haemost 1989; 61: 502-506
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 18 Hoffmann JJML, Bonnier JJRM. Histidine-rich glycoportein in thrombolytic therapy: has it clinical relevance?. Blood Coag Fibrinol 1991; 2: 237-241
    CrossrefPubMedGoogle Scholar
  • 19 Hoffmann JJML, Vijgen M. Prevention of in vitro fibrinogenolysis during laboratory monitoring of thrombolytic therapy with streptokinase or APSAC. Blood Coag Fibrinol 1991; 2: 279-284
    CrossrefPubMedGoogle Scholar
  • 20 Friberger P. Methods for determination of plasmin, antiplasmin and plasminogen by means of substrate S-2251. Haemostasis 1978; 7: 138-145
    PubMedGoogle Scholar
  • 21 Becker U, Bartl S, Wahlefield A. A functional photometric assay for plasma fibrinogen. Thromb Res 1984; 35: 475-479
    CrossrefPubMedGoogle Scholar
  • 22 Gallimore M, Fareid E. Studies on human inhibitors of plasmin, plasma kallikrein, trypsin, thrombin and urokinase using chromogenic substrate assays. In: Chromogenic peptide substrates. Scully MF, Kakkar VV. (eds). London: Churchill Livingstone; 1979: 248-261
    Google Scholar
  • 23 Alkjaersig N, Fletcher AP, Sherry S. The mechanism of clot dissolution by plasmin. J Clin Invest 1959; 38: 1086-1095
    CrossrefPubMedGoogle Scholar
  • 24 Thorsen S. Differences in the binding to fibrin of native plasminogen and plasminogen modified by proteolytic degradation. Influence of E-aminocarboxylic acids. Biochim Biophys Acta 1975; 393: 55-65
    CrossrefPubMedGoogle Scholar
  • 25 Rakoczi I, Wiman B, Collen D. On the biologic significance of the specific interaction between fibrin, plasminogen, and antiplasmin. Biochim Biophys Acta 1978; 540: 295-300
    CrossrefPubMedGoogle Scholar
  • 26 Lucas MA, Fretto LJ, McKee PA. The binding of human plasminogen to fibrin and fibrinogen. J Biol Chem 1983; 258: 4249-4256
    PubMedGoogle Scholar
  • 27 Collen D. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78: 3114-3124
    PubMedGoogle Scholar
  • 28 Gardell SJ, Hare TR, Bergum PW, Cuca GC, O’Neill-Palladino L, Zavodny SM. Vampire bat salivary plasminogen activator is quiescent in human plasma in the absence of fibrin unlike human tissue plasminogen activator. Blood 1990; 76: 2560-2564
    PubMedGoogle Scholar
  • 29 Hare TR, Gardell SJ. Vampire bat salivary plasminogen activator promotes'robust lysis of plasma clots in a plasma milieu without causing fluid phase plasminogen activation. Thromb Haemost 1992; 68: 165-169
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 30 Sherry S, Marder VJ. Thrombosis, fibrinolysis, and thrombolytic therapy: A perspective. Progr Cardiovasc Dis 1991; XXIV: 089-100
    PubMedGoogle Scholar
  • 31 Rao AK, Pratt C, Berke A, Jaffe A, Ockene I, Schreiber TL, Bell WR, Knatterud G, Robertson TL, Terrin ML. Thrombolysis in myocardial infarction (TIMI) trial – Phase I: Hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11: 01-11
    CrossrefPubMedGoogle Scholar
  • 32 Sabovic M, Lijnen HR, Keber D, Collen D. Effect of retraction on the lysis of human clots with fibrin specific and non-fibrin specific plasminogen activators. Thromb Haemostas 1989; 62: 1083-1087
    PubMedGoogle Scholar
  • 33 Andrew M, Brooker L, Leaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost 1992; 68: 325-330
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 34 Kakkar W, Sagar S, Lewis M. Treatment of deep-vein thrombosis with intermittent streptokinase and plasminogen infusion. Lancet 1975; 2: 674-676
    PubMedGoogle Scholar
  • 35 Anderle K, Fröhlich A. Review of studies with plasminogen concentrates and proposals for further therapeutic strategies with plasminogen concentrates. Haemost 1988; 18 (Suppl. 01) 165-175
    CrossrefPubMedGoogle Scholar
  • 36 Urokinase pulmonary embolism trial. Phase 1 results. A cooperative study JAMA 1970; 214: 2163-2172
    CrossrefPubMedGoogle Scholar
  • 37 Gottlob R, El Nashef B, Donas P, Piza F, Kolb R. Studies on thrombolysis with streptokinase.IV. Immunofluorescent investigations on the fibrin pattern and the content of plasminogen and of plasma-plasmin-inhibitors in clots and thrombi of various age. Thromb Diath Haemorrh 1973; XXIX: 393-407
    PubMedGoogle Scholar