Summary
In this study, the in-vitro fibrinolytic efficacy of Tenecteplase, Amediplase and
scu-PA was investigated in different external lysis models by measuring the lysis
of human plasma clots after the addition of the plasminogen activators (PAs) to the
surrounding plasma. The effect ofTAFI was examined for each PA by neutralizing TAFI
a with potato carboxypeptidase inhibitor (PCI). The lytic efficacy of Amediplase was
lower than that of Tenecteplase at low PA concentrations but slightly higher at therapeutic
concentrations. The activity of scu-PA was clearly lower than that of either Tenecteplase
or Amediplase. The TAFI system inhibited external clot lysis mediated by all the PAs
when thrombomodulin was present in the model. In the therapeutic range (5–10 µg/ml)
however, the TAFIa effect was negligible for both Amediplase and Tenecteplase. At
lower PA concentrations the effect of TAFI on Amediplase was slightly stronger than
that on Tenecteplase. Under static conditions the lysis rates were lower than with
stirring. The role of TAFI was similar under both conditions. In conclusion, at therapeutic
concentrations Amediplase was slightly more active than Tenecteplase and scu-PA under
all conditions used. Therefore, Amediplase might possibly be a more potent thrombolytic
agent at these concentrations and increase the efficacy of thrombolysis. The potential
of TAFI for inhibiting thrombolytic therapy is probably low. However in conditions
where the local PA concentrations are sub-optimal TAFI might affect the lysis rate.
Keywords
TAFI - plasminogen activator - fibrinolysis - thrombolysis - Amediplase - Tenecteplase
