The identification, cloning, and sequencing of the gene for human factor IX have led to a more thorough understanding of the protein's biochemical properties and function in normal coagulation, an appreciation of the molecular pathogenesis of factor IX deficiency (hemophilia B), and the ability to accurately identify hemophilia B carriers and affected fetuses in families at risk. Until recently, carrier detection methods relied almost exclusively on assays that measure the functional and antigenic activity of the factor IX protein in plasma. Analysis of linkage between a hemophilia B mutation and one or more restriction fragment length polymorphisms improves the accuracy of carrier detection and prenatal diagnosis, but its applicability is limited to informative family members. The first part of this article reviews recent publications that describe the use of polymerase chain reaction both to characterize new factor IX gene mutations in persons with hemophilia B and facilitate accurate assignment of carrier status in women at risk. The second part focuses on recent developments in the preparation of factor IX concentrates for the treatment and prevention of hemophilia B-related bleeding. Several high-purity factor IX concentrates have been developed and are either currently being evaluated in clinical trials or are awaiting licensure by the US Food and Drug Administration. These new products have significantly higher specific activity than currently available factor IX concentrates and are associated with little or no risk of thrombotic complications. In particular, ultrapure factor IX prepared by monoclonal antibody affinity chromatography does not contain detectable quantities of other vitamin K-dependent proteins and appears safe from the standpoint of blood-borne virus infection risk.
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