Fibrinolytic efficacy of Amediplase, Tenecteplase and scu-PA in different external plasma clot lysis models: sensitivity to the inhibitory action of thrombin activatable fibrinolysis inhibitor (TAFI).
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 of TAFI was examined for each PA by neutralising TAFIa 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 mug/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.
Guimarães
Ana H C
AH
Department of Hematology, Erasmus University Medical Center Rotterdam, The Netherlands.
Barrett-Bergshoeff
Marrie M
MM
Criscuoli
Marco
M
Evangelista
Stefano
S
Rijken
Dingeman C
DC
D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D025901:Carboxypeptidase B2 / Q000494:pharmacology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D005337:Fibrin / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D010960:Plasminogen Activators; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D011198:Solanum tuberosum; D000077785:Tenecteplase; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism* / Q000494:pharmacology
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; C473928:amediplase; D005337:Fibrin; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D000077785:Tenecteplase