Thrombosis research
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Thrombosis research · Oct 1986
Comparative StudyA comparative study of the efficacy and specificity of tissue plasminogen activator and pro-urokinase: demonstration of synergism and of different thresholds of non-selectivity.
Clot lysis and non-specific plasminogen activation in human plasma by tissue tissue plasminogen activator (t-PA) and/or pro-urokinase (pro-UK) were studied. The fibrinolytic activity of pro-UK was expressed as latent units, i.e. measured after activation with plasmin on a fibrin plate against the reference standard. The t-PA unitage was assigned on a weight basis of a similar equivalence of 100,000 IU/mg. ⋯ Non-specific plasminogen activation occurred above a certain concentration of either activator but was found at lower concentrations of t-PA than pro-UK. In the absence of a clot, plasmin generation occurred with t-PA at about 30% of the concentration at which pro-UK induced a corresponding effect. It is concluded that there are important differences in the fibrinolytic and clot selective properties of t-PA and pro-UK, and that some of these properties may be complementary resulting in a fibrin specific, synergistic fibrinolytic effect.
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Fibrinogen Aarhus was found in a woman with slightly prolonged whole blood clotting time. The thrombin induced clotting of plasma and purified fibrinogen was much prolonged. Kinetic analysis of FPA and FPB release revealed larger apparent Km and Vmax values for fibrinogen Aarhus than for normal fibrinogen. ⋯ The turbidity of fibrin gels obtained from fibrinogen Aarhus was similar to normal fibrin gels at low thrombin concentrations. Increasing thrombin concentration resulted in appearance of degradation products in the fibrin gels from fibrinogen Aarhus and at the same time a relative increase in turbidity of the gels was observed. Possibly reasons for the slow release of fibrinopeptides, the delayed gelation, and susceptibility to degradation by thrombin are discussed.
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Thrombosis research · Apr 1986
Effects of tranexamic acid on fibrinolysis, fibrinogenolysis and amidolysis.
When Glu-plasminogen (Glu-plg) was activated by urokinase (UK) in the presence of fibrinogen or fibrinogen plus tranexamic acid (1 mM), or else tranexamic acid (1 mM), the activation as measured by the hydrolysis of S-2251 was enhanced by tranexamic acid or fibrinogen or both. When plasma or clotted plasma was activated by UK in the presence of 1 mM tranexamic acid, fibrinolysis was completely inhibited. When Lys-plg was activated by UK in the presence of tranexamic acid and fibrin or fibrinogen, fibrinolysis was completely inhibited by 1 mM tranexamic acid, but some inhibition of fibrinogenolysis was observed. ⋯ The release of B beta 15-42 from fibrin after UK-activation of Lys-plg was partly inhibited by tranexamic acid. In conclusion, tranexamic acid in the concentration of 1 mM enhanced amidolysis, but inhibted fibrinolysis measured by the generation of fibrin-degradation products. Fibrinogenolysis and the release of B beta 15-42 from fibrin were partly inhibited.
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Thrombosis research · Aug 1985
Protraction of whole blood and plasma clot lysis in patients with high levels of an inhibitor of tissue-type plasminogen activator.
The influence of the newly discovered, fast-acting inhibitor of tissue-type plasminogen activator (t-PA) on the lysis time of plasma clots was studied by visual observation of lysis of clotted citrated plasma after addition of purified t-PA. To a series of plasma samples with various concentrations of naturally occurring PA-inhibitor purified t-PA was added to a final concentration, which in pooled normal plasma is sufficient to induce clot lysis within a few hours. ⋯ Lysis rate, read from the appearance of radioactivity in the serum after centrifugation, was significantly lower in clots obtained from subjects with a high free inhibitor level than in those with a low inhibitor level. It is concluded that the PA-inhibitor protracts clot lysis and may be relevant for physiological fibrinolysis.