Plasmin inhibitors in the prevention of systemic effects during thrombolytic therapy: specific role of the plasminogen-binding form of alpha 2-antiplasmin.
To delineate the role of plasmin inhibitors, especially the two molecular forms of alpha 2-antiplasmin (that is, the plasminogen-binding and the nonplasminogen-binding forms), in the control of systemic effects during thrombolytic therapy, the consumption of plasmin inhibitors and the degree of fibrinogen breakdown were studied in 35 patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA) or streptokinase. At a low degree of plasminogen activation (in six patients treated with rt-PA), plasminogen-binding alpha 2-antiplasmin was consumed first. At a higher degree of plasminogen activation (in 20 patients), plasminogen-binding alpha 2-antiplasmin became exhausted (less than 20%) and other plasmin inhibitors (that is, nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin) were consumed. After extensive plasminogen activation (in nine patients treated with streptokinase), plasminogen-binding alpha 2-antiplasmin consumption was complete and nonplasminogen-binding alpha 2-antiplasmin and alpha 2-macroglobulin were consumed to about 30% to 50% of the pretreatment level. No significant C1-inactivator consumption occurred, even at extreme degrees of plasminogen activation. Fibrinogen breakdown as a marker for systemic effects correlated strongly with consumption of plasminogen-binding alpha 2-antiplasmin. Fibrinogen breakdown did occur, but only when the amount of plasminogen-binding alpha 2-antiplasmin was decreased to less than 20% of the pretreatment level. The other plasmin inhibitors could not prevent fibrinogen breakdown. These results were confirmed by in vitro studies. It is concluded that plasminogen-binding alpha 2-antiplasmin is the most important inhibitor of plasmin in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Gaubius Institute, TNO, Leiden, The Netherlands.
F W
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Leebeek
C
C
Kluft
E A
EA
Knot
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P
Los
A F
AF
Cohen
A J
AJ
Six
D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D004334:Drug Administration Schedule; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D010958:Plasminogen / Q000378:metabolism; D013300:Streptokinase / Q000627:therapeutic use*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D000979:alpha-2-Antiplasmin / Q000378:metabolism / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000378:metabolism / Q000502:physiology*
D003174:Complement C1 Inactivator Proteins; D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D005340:Fibrinogen; D010958:Plasminogen; D013300:Streptokinase; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin