Potential Application of Recombinant Snake Prothrombin Activator Ecarin in Blood Diagnostics

Biomolecules. 2022 Nov 17;12(11):1704. doi: 10.3390/biom12111704.

Abstract

We describe here the purification and cloning of a codon-optimized form of the snake prothrombin activator ecarin from the saw scaled viper (Echis carinatus) expressed in mammalian cells. Expression of recombinant ecarin (rEcarin) was carried out in human embryonic kidney cells (HEK) cells under conditions for the development and performance of a novel and scalable recombinant snake ecarin to industry standards. Clotting performance of the rEcarin was established in recalcified citrated whole blood, plasma, and fresh whole blood and found to be comparable to native ecarin (N-Ecarin). Furthermore, hemolysis was observed with N-Ecarin at relatively high doses in both recalcified citrated and fresh whole blood, while clotting was not observed with rEcarin, providing an important advantage for the recombinant form. In addition, rEcarin effectively clotted both recalcified citrated whole blood and fresh whole blood containing different anticoagulants including heparin, warfarin, dabigatran, Fondaparinux, rivaroxaban and apixaban, forming firm clots in the blood collection tubes. These results demonstrate that rEcarin efficiently clots normal blood as well as blood spiked with high concentrations of anticoagulants and has great potential as an additive to blood collection tubes to produce high quality serum for analyte analysis in diagnostic medicine.

Keywords: blood clotting; clotting of anticoagulated blood; high quality serum; recombinant ecarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / pharmacology
  • Endopeptidases* / pharmacology
  • Humans
  • Prothrombin* / metabolism
  • Snakes
  • Thromboplastin
  • Thrombosis*
  • Viper Venoms* / pharmacology

Substances

  • Anticoagulants
  • ecarin
  • Prothrombin
  • Thromboplastin
  • Viper Venoms
  • Endopeptidases

Grants and funding

We appreciate all financial support of Q-Sera for funding for the project “QSera: a novel serum collection tube” grant number T10473-D01/AG-027735.