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

Stroke. 2020 Jul;51(7):2236-2239. doi: 10.1161/STROKEAHA.120.028793. Epub 2020 Jun 17.

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.

Keywords: anticoagulants; fibrinolysis; protein C; tenecteplase; tissue-type plasminogen activator.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Fibrinolysis / drug effects*
  • Fibrinolytic Agents / pharmacology*
  • Humans
  • In Vitro Techniques
  • Protein C / pharmacology*
  • Recombinant Proteins / pharmacology*
  • Tenecteplase / pharmacology*
  • Thrombosis

Substances

  • 3K3A-APC protein
  • Fibrinolytic Agents
  • Protein C
  • Recombinant Proteins
  • Tenecteplase