Hemophilia A-From Basic Science to Clinical Practice

Jens Klinge; Natalya M. Ananyeva; Charlotte A. E. Hauser; Evgueni L. Saenko

doi:10.1055/s-2002-32667

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2002; 28(3): 309-322
DOI: 10.1055/s-2002-32667

Hemophilia A-From Basic Science to Clinical Practice

Jens Klinge¹ , Natalya M. Ananyeva² , Charlotte A.E. Hauser³ ⁴ , Evgueni L. Saenko² ⁵

¹Hospital for Children and Adolescents, University of Erlangen, Erlangen, Germany
²J. Holland Laboratory, American Red Cross, Rockville, Maryland
³Octagene Biomedical Laboratories, Martinsried, Germany
⁴Department of Obstetrics and Gynecology, Medical University of Lübeck, Lübeck, Germany
⁵George Washington University School of Medicine, Washington, DC

Abstract

ABSTRACT

This article summarizes achievements of basic research and their implementation in clinical treatment of one of the most common inherited bleeding disorders hemophilia A, which is caused by genetic deficiency of coagulation factor VIII (FVIII). We discuss the structure of FVIII, its major interactions in the intrinsic pathway of blood coagulation, and the catabolism of FVIII. We also discuss achievements in the contemporary clinical practice of treatment of hemophilia A. Replacement therapy has substantially improved by development of purification and virus inactivation procedures, allowing preparation of safe and effective therapeutic plasma-derived FVIII concentrates. We give special attention to the principles used in the development of contemporary recombinant FVIII products, which do not inherit a potential risk for viral or prion transmission. Development of FVIII inhibitory antibodies is the major complication of FVIII replacement therapy. We summarize the accumulated knowledge regarding epitopes of FVIII inhibitors and mechanisms by which they inactivate FVIII and discuss approaches to overcome the effects of inhibitors and to prevent their formation by induction of immunotolerance. We also analyze the main concepts and scientific priorities in the gene-therapeutic approach for treatment of hemophilia A.

KEYWORDS

Hemophilia A - factor VIII - replacement therapy - inhibitors - gene therapy

Full Text

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