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
1   Department of Hematology, Erasmus University Medical Center, Rotterdam,Italy
,
Marrie M. Barrett-Bergshoeff
2   TNO Quality of Life, Biomedical Research, Gaubius Laboratory, Leiden, the Netherlands, Italy
,
Marco Criscuoli
3   Menarini Ricerche, Preclinical Development Department, Florence, Italy
,
Stefano Evangelista
3   Menarini Ricerche, Preclinical Development Department, Florence, Italy
,
Dingeman C. Rijken
1   Department of Hematology, Erasmus University Medical Center, Rotterdam,Italy
› Author Affiliations
Financial support: This study was financially supported by Menarini Ricerche S.p.A., Rome, Italy.
Further Information

Publication History

Received 10 April 2006

Accepted after resubmission 28 July 2006

Publication Date:
30 November 2017 (online)

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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.