Fibrinolytic efficacy of Amediplase, Tenecteplase and scu-PA in different external plasma clot lysis models

Ana H. C. Guimarães; Marrie M. Barrett-Bergshoeff; Marco Criscuoli; Stefano Evangelista; Dingeman C. Rijken

doi:10.1160/TH06-04-0197

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(03): 325-330
DOI: 10.1160/TH06-04-0197

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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)

Ana H. C. Guimarães

¹Department of Hematology, Erasmus University Medical Center, Rotterdam,Italy

,

Marrie M. Barrett-Bergshoeff

²TNO Quality of Life, Biomedical Research, Gaubius Laboratory, Leiden, the Netherlands, Italy

,

Marco Criscuoli

³Menarini Ricerche, Preclinical Development Department, Florence, Italy

,

Stefano Evangelista

³Menarini Ricerche, Preclinical Development Department, Florence, Italy

,

Dingeman C. Rijken

¹Department of Hematology, Erasmus University Medical Center, Rotterdam,Italy

› Author Affiliations

Abstract

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

Full Text

References

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