Inhibitor-Resistant Tissue-Type plasminogen activator: An improved thrombolytic agent in vitro

R. V. Shohet, S. Spitzer, E. L. Madison, R. Bassel-Duby, M. J. Gething, J. F. Sambrook

Research output: Contribution to journalArticle

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Abstract

Platelet-rich clots are inefficiently lysed by current fibrinolytic agents. Platelets contain a great deal of plasminogen activator inhibitor 1 (PAI-1), the principal endogenous inhibitor of tissue-type plasminogen activator (t-PA). We have tested whether PAI-1 resistant t-PAs would be more effective thrombolytic agents in an in vitro model of platelet-rich clots. Clots were formed with recalcified human plasma without or with the addition of platelets. The lysis of these clots was followed by the release of incorporated 125I-fibrinogen. Mutant and wild-type t-PA were almost equally effective against clots lacking platelets but the mutant was twice as effective at lysing platelet-rich clots. A mechanism for this effect is suggested by the demonstration that a complex between wild-type t-PA and extruded platelet contents resembles that between purified t-PA and PAI-1 and that the PAI-1 resistant t-PA does not interfere with formation of this adduct. Because of its enhanced ability to lyse platelet-rich clots in vitro, further in vivo work may find that PAI-1 resistant t-PA is a more efficacious therapeutic agent than wild-type t-PA in situations where platelets contribute to the failure of thrombolysis.

Original languageEnglish (US)
Pages (from-to)124-128
Number of pages5
JournalThrombosis and Haemostasis
Volume71
Issue number1
StatePublished - 1994

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Fibrinolytic Agents
Tissue Plasminogen Activator
Plasminogen Activator Inhibitor 1
Blood Platelets
Plasminogen Activators
In Vitro Techniques
Fibrinogen

ASJC Scopus subject areas

  • Hematology

Cite this

Shohet, R. V., Spitzer, S., Madison, E. L., Bassel-Duby, R., Gething, M. J., & Sambrook, J. F. (1994). Inhibitor-Resistant Tissue-Type plasminogen activator: An improved thrombolytic agent in vitro. Thrombosis and Haemostasis, 71(1), 124-128.

Inhibitor-Resistant Tissue-Type plasminogen activator : An improved thrombolytic agent in vitro. / Shohet, R. V.; Spitzer, S.; Madison, E. L.; Bassel-Duby, R.; Gething, M. J.; Sambrook, J. F.

In: Thrombosis and Haemostasis, Vol. 71, No. 1, 1994, p. 124-128.

Research output: Contribution to journalArticle

Shohet, RV, Spitzer, S, Madison, EL, Bassel-Duby, R, Gething, MJ & Sambrook, JF 1994, 'Inhibitor-Resistant Tissue-Type plasminogen activator: An improved thrombolytic agent in vitro', Thrombosis and Haemostasis, vol. 71, no. 1, pp. 124-128.
Shohet, R. V. ; Spitzer, S. ; Madison, E. L. ; Bassel-Duby, R. ; Gething, M. J. ; Sambrook, J. F. / Inhibitor-Resistant Tissue-Type plasminogen activator : An improved thrombolytic agent in vitro. In: Thrombosis and Haemostasis. 1994 ; Vol. 71, No. 1. pp. 124-128.
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