3K3A-Activated Protein C Variant Does Not Interfere With the Plasma Clot Lysis Activity of Tenecteplase

Overview

Journal Stroke

Specialties Cardiology & Vascular Diseases
Neurology

Date 2020 Jun 23

PMID 32568648

Authors

Purba Mukherjee

Patrick Lyden

Jose A Fernandez

Thomas P Davis

Kent E Pryor

Berislav V Zlokovic

John H Griffin

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: A recombinant engineered variant of APC (activated protein C), 3K3A-APC, lacks anticoagulant properties (<10%) while preserving APCs anti-inflammatory, anti-apoptotic, and neuroprotective functions and is very promising in clinical trials for ischemic stroke. Therapeutic intervention with single bolus administration of the third-generation tPA (tissue-type plasminogen activator), tenecteplase, is anticipated to be widely adopted for treatment of acute ischemic stroke. 3K3A-APC is well-tolerated in stroke patients dosed with alteplase, and in vitro studies show 3K3A-APC does not interfere with alteplase-induced clot lysis. The purpose of this in vitro study was to assess the influence of 3K3A-APC on tenecteplase-induced clot lysis.

Methods: Tenecteplase-mediated lysis of thrombin generated plasma clots of human normal pooled plasma was monitored in the presence of varying doses of 3K3A-APC. The effects on fibrinolysis by tenecteplase and alteplase were compared.

Results: The presence of 3K3A-APC shortened the time for clot lysis induced by tenecteplase at very low levels but not at higher therapeutic concentrations of tenecteplase. Comparisons of alteplase-mediated clot lysis to tenecteplase clot lysis showed that both thrombolytic agents behaved similarly in the presence of 3K3A-APC.

Conclusions: These results indicate that 3K3A-APC does not interfere with tenecteplase's clot lysis function.

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