Recombinant Antithrombin: Production and Role in Cardiovascular Disorder

Jerrold H. Levy; Andrew Weisinger; Carol A Ziomek; Yann Echelard Ph D

doi:10.1055/s-2001-16893

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2001; 27(4): 405-416
DOI: 10.1055/s-2001-16893

Recombinant Antithrombin: Production and Role in Cardiovascular Disorder

Jerrold H. Levy¹ , Andrew Weisinger¹ , Carol A Ziomek² , Yann Echelard Ph.D.²

¹Departments of Anesthesiology, Emory University School of Medicine, and Division of Cardiothoracic Anesthesiology and Critical Care, Emory Healthcare, Atlanta, Georgia
²Genzyme Transgenics Corporation, Framingham, Massachusetts

Abstract

ABSTRACT

Plasma-derived antithrombin (AT) concentrates have been used for the management of hereditary and acquired deficiencies since the early 1980s. Recombinant versions of other blood factors and their derivatives are increasingly becoming available, providing a safe and abundant supply of these important therapeutics. However, the complexity of the AT molecule and the large doses often required for supplementation treatments preclude the use of traditional cell culture bioreactors for recombinant production. The development of a very efficient expression system has been necessary for the cost-efficient recombinant production of AT. Transgenic production, with its ability to yield high levels of heterologous protein and its scale-up flexibility, is an attractive alternative to plasma fractionation. Purification of recombinant AT from the milk of transgenic dairy goats has been developed to provide a homogeneous, well-defined, and abundant supply of this factor. This article describes the production of recombinant AT and aspects of clinical applications of this molecule to cardiovascular disorders.

KEYWORD

Recombinant antithrombin - transgenic production - cardiopulmonary bypass - heparin resistance - clinical trials

Full Text

References

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