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• W2148221103 endingPage "2078" @default.
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• W2148221103 abstract "We compared the activity of a new long-half-life, fibrin-specific tissue-type plasminogen activator (TPA) variant with that of wild-type TPA in rabbit models of embolic stroke and peripheral bleeding. In the embolic stroke model. TPA-induced clot lysis is followed by continuous monitoring of a radiolabeled clot lodged in the middle cerebral artery. Twenty-four hours after embolization and treatment with either thrombolytic agent or excipient, the brains are removed, fixed, and evaluated for cerebral hemorrhage. In a parallel template bleeding time experiment, the effects of equipotent doses of the two TPA molecules were measured. Infusion of wild-type TPA or bolus administration of the TPA variant resulted in dose-dependent clot lysis. The TPA variant was found to be an order of magnitude more potent than wild-type TPA on a milligram-per-kilogram basis. Unlike wild-type TPA, the variant caused less systemic activation of plasminogen (P < .05) and fewer hemorrhagic transformations in this model (P < .05). The TPA variant did not extend template bleeding times. These findings show that by combining increased fibrin specificity with decreased plasma clearance, it is possible to produce a thrombolytic agent that is more convenient and more potent than wild-tpe TPA. At the same time the significant reduction in hemorrhagic conversions may be attributable to the conservation of systemic plasminogen seen with this molecule." @default.
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• W2148221103 date "1994-10-01" @default.
• W2148221103 modified "2023-09-27" @default.
• W2148221103 title "A long-half-life and fibrin-specific form of tissue plasminogen activator in rabbit models of embolic stroke and peripheral bleeding." @default.
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• W2148221103 doi "https://doi.org/10.1161/01.str.25.10.2072" @default.
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