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

Purba Mukherjee, Patrick Lyden, José A. Fernández, Thomas P. Davis, Kent E. Pryor, Berislav V. Zlokovic, John H. Griffin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2236-2239
Number of pages4
JournalStroke
DOIs
StateAccepted/In press - 2020

Keywords

  • anticoagulants
  • fibrinolysis
  • protein C
  • tenecteplase
  • tissue-type plasminogen activator

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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