Depletion of plasminogen in vitro or during thrombolytic therapy limits fibrinolytic potential

Pall T. Onundarson, Charles W. Francis, Victor J. Marder

Rannsóknarafurð: Framlag til fræðitímaritsGreinritrýni

38 Tilvitnanir (Scopus)

Útdráttur

Thrombolytic therapy frequently induces a "lytic state" associated with a decrease in plasma plasminogen concentration that could limit therapeutic efficacy. We therefore investigated the influence of soluble plasminogen concentration on in vitro lysis of retracted whole-blood clots in plasma from normal subjects and from patients undergoing thrombolytic therapy. With recombinant tissue plasminogen activator (1000 ng/ml) or two-chain urokinase plasminogen activator (250 U/ml), minimal clot lysis occurred in normal plasma depleted of plasminogen by lysine Sepharose chromatography. Clot lysis induced by two-chain urokinase plasminogen activator increased progressively in normal plasma at initial plasminogen concentrations between 0.06 to 6 U/ml, whereas maximum lysis with recombinant tissue plasminogen activator occurred between 0.5 U/ml and 1 U/ml and was less at lower and higher concentrations of plasminogen. Incubation of whole-blood clots in normal plasma with recombinant tissue plasminogen activator resulted in little change in plasminogen concentration during 6 hours, with a constant rate of clot lysis. Incubation with two-chain urokinase plasminogen activator, however, caused a rapid decrease in plasminogen concentration and a corresponding decrease in lysis rate; lysis rate was restored after repletion with purified plasminogen. The effect of in vivo activator-induced plasminogen depletion on in vitro clot lysis rates was tested with plasma obtained from patients 90 to 120 minutes after they had received 30 mg of acylated plasminogen-streptokinase activator complex that showed depletion of plasminogen to 14% ± 2%. These plasma samples produced only 4% ± 1% in vitro clot lysis during 4 hours but lysis increased progressively after repletion with 1, 2, and 4 U/ml plasminogen. The data suggest that the reduction in plasminogen associated with the lytic state attenuates thrombolysis, and that the therapeutic efficacy of thrombolytic agents may be optimized by preventing plasminogen depletion.

Upprunalegt tungumálEnska
Síður (frá-til)120-128
Síðufjöldi9
FræðitímaritThe Journal of Laboratory and Clinical Medicine
Bindi120
Númer tölublaðs1
ÚtgáfustaðaÚtgefið - júl. 1992

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