Tissue-type plasminogen activator t-PA

Kluft C., Verheijen J. H. Leiden Fibrinolysis Working Party. Blood collection and handling procedures for assessment of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). Fibrinolysis 1990 4(Suppl2) 155-61. 

Tissue paper products, 13 129-130 Tissue plasminogen activator (t-PA) bioseparation from mammalian cell culture, 3 821-826 peptide map, 3 841, 842 selling price, 3 817t Tissue reactions, to sutures, 24 218 Tissue-type plasminogen activator (t-PA) and hemostatic system, 4 89 human, use as thrombolytic agent,... 

Rijken DC, Otter M, Kuiper J, van Berkel TJ. Receptor-mediated endocytosis of tissue-type plasminogen activator (t-pa) by liver cells. Thromb Res Suppl 1990 10 63-71. 

Diaz, V. M., Hurtado, M., Thomson, T. M., Reventos, )., Paciucci, R. (2004). Specific interaction of tissue-type plasminogen activator (t-PA) with... 

Pannekoek, H., de Vries, C., and von Zonneveld, A-J. (1988). Mutants of tissue-type plasminogen activator (t-PA) structural aspects and functional properties. Fibrinolysis 2,123 132. 

Tissue-type plasminogen activator (t-PA) Plasminogen activation Thrombolysis 32... 

As wounds heal, clots must be removed. The principal agent for dissolving clots is an enzyme called plasmin, which is synthesized as the inactive zymogen called plasminogen. Plasminogen is activated by a number of proteases, the most important of which is tissue-type plasminogen activator (t-PA). t-PA can be extremely effective in initiating the cascade to dissolve the unwanted blood clot involved in stroke or heart attack. 

The fibrinolytic system is activated in response to the presence of an intracellular thrombus or clot. The process of clot dissolution is initiated by the conversion of plasminogen to plasmin. Plasminogen activation is catalyzed by two endogenous highly specific serine proteases, urokinase-type plasminogen activator and tissue-type plasminogen activator (t-PA) (see Chapter 31). 

From 1995 through 2002, we participated in four international randomized studies and one collaborative study with the University of Vermont in which pharmacological thrombolysis was employed with alteplase [tissue-type plasminogen activator (t-PA)] or tenecteplase [TNK-t-PA (TNK)]. In this chapter we summarize our experience with the cohorts of patients in all of these studies who were studied in the United Arab Emirates (UAE). The first of the studies was the Continuous Infusion versus Double Bolus of Alteplase (COBALT) study. The other three were Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT I, II, III) studies and a substudy in ASSENT II with the University of Vermont (4-8). The last study, a collaborative one with the University of Vermont, was the Enhanced Rapidity of RECanah-zation with Tenecteplase compared with Alteplase (ERRECTA) study, results of which have not yet been published. All of the patients participating in ERRECTA were patients in the UAE. 

The GUSTO trial demonstrated that treatment of patients within 6 hours after onset of symptoms with the combination of a clot-selective thrombolytic agent [recombinant tissue type plasminogen activator (t-PA)] plus conjunctive treatment with aspirin and intravenous unfractionated heparin resulted in 30-day mortality of 6.3% (6). An angiographic substudy demonstrated that patency of the infarct-related artery was not the sole determinant of outcome. Restoration of normal coronary flow after thrombolysis was found to be critical in lowering mortality (7). Thus, angiographic analysis demonstrated that both induction of culprit artery patency and the extent of restoration of flow were determinants of outcome. 

Wl. Wagner, O. F., de Vries, C., Hohmann, C., Veerman, H., and Pannekoek, H., Interaction between plasminogen activator inhibitor-1 (PAI-1) bound to fibrin and either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) Binding of t-PA/PAI-1 complexes to fibrin mediated by both the finger and kringle-2 domain of t-PA. J. Clin. Invest. 84, 647-655 (1989). 

Hedley, M.L., Curley, J. and Urban, R., 1998. Microspheres containing plasmid-encoded antigens elicit cytotoxic T-cell responses. Nature Medicine, 4(3), 365-368. Heeremans, J.L. et al, 1995. Thrombolytic treatment with tissue-type plasminogen activator (t-PA) containing liposomes in rabbits a comparison with free t-PA. Thromb. Haemost., 73(3), 488-494. 

Bu, G., Morton, P. A., and Schwartz, A. L. (1992a) Identification and partial characterization by chemical cross-linking of a binding protein for tissue-type plasminogen activator (t-PA) on rat hepatoma cells. /. Biol. Chem. 267, 15595-15602. 

Kruithof, E.K.O., 1988, Inhibitors of plasminogen activators. In Tissue-Type Plasminogen Activator (t-PA) Physiological and Clinical Aspects (C. Kluft, Ed.), CRC Press, Inc., Boca Raton, pp 189-210. 

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