Response of Factor VIII and IX-Deficient Blood to Wild Type and High Membrane Affinity Mutant Factor VIIa in an In Vitro Whole Blood Clotting Assay: Possible Correlation to Clinical Outcome

Nicole Henderson; Nigel S. Key; Beverly Christie; Walter Kisiel; Donald Foster; Gary L. Nelsestuen

doi:10.1055/s-0037-1613160

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2002; 88(01): 98-103
DOI: 10.1055/s-0037-1613160

Review Article

Schattauer GmbH

Response of Factor VIII and IX-Deficient Blood to Wild Type and High Membrane Affinity Mutant Factor VIIa in an In Vitro Whole Blood Clotting Assay: Possible Correlation to Clinical Outcome

Nicole Henderson

¹Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul, MN

,

Nigel S. Key

²Department of Medicine, University of Minnesota, Minneapolis, MN

,

Beverly Christie

²Department of Medicine, University of Minnesota, Minneapolis, MN

,

Walter Kisiel

³University of New Mexico, Albuquerque, New Mexico

,

Donald Foster

⁴ZymoGenetics, Seattle, WA, USA

,

Gary L. Nelsestuen

¹Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, St. Paul, MN

› Institutsangaben

Abstract

Summary

A modified form of the activated whole blood clotting time was used to evaluate response of blood from hemophilia patients to factor VIIa. Repeated assays of individuals over a one-year period showed consistency for each individual and significant difference between individuals. Four hemophilia patients with inhibitors gave low response to factor VIIa in the assay and were characterized as low or moderate clinical responders to factor VIIa therapy. Another four patients with moderate to good clinical responsiveness to factor VIIa therapy showed a strong response to factor VIIa in the assay. A factor VIIa mutant with enhanced membrane affinity showed 10 to 13-fold higher activity than wild type factor VIIa. The results may justify larger studies to determine the utility of this assay for evaluation of patient responsiveness and to set factor VIIa therapy levels.

Keywords

Factor VIIa - hemophilia

Volltext

Referenzen

References
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