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Tolerance

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  • Adapted From:   Van Parijs: Science, Volume 280(5361).April 10, 1998.243-248
  • Inhibitor Impact Inhibitors have a major impact on treatment outcome. When inhibitors are present, hemostasis is often difficult to control. Therefore normal therapy typically fails, which leads to increased morbidity and mortality. The presence of inhibitors is also associated with the decreased ability to perform needed or elective surgery. FIX inhibitors pose specific problems in treatment. (See next slide.)
  • Overview Inhibitors are antibodies that counteract the therapeutic actions of factor concentrates currently used to treat hemophilia bleeding episodes. Inhibitor development therefore represents one of the greatest obstacles for physicians caring for persons with coagulation disorders. In the first part of today’s presentation, the prevalence and impact of coagulation factor inhibitors will be addressed. In addition, the advantages and disadvantages of current inhibitor treatment options will be presented. The second part of the presentation will discuss recombinant factor VIIa, a new therapeutic agent for managing bleeds in patients with inhibitors to FVIII or FIX. The mechanism of action and production of rFVIIa as well as preclinical and clinical rFVIIa data will also be presented. The final part of the presentation will address future challenges concerning the use of rFVIIa in the treatment and maintenance of bleeding episodes in inhibitor patients.
  • Inhibitors Inhibitors in persons with hemophilia A or hemophilia B are almost always alloantibodies of the IgG immunoglobulin class and are of the IgG1 and IgG4 subtypes. Inhibitors occur either in congenital deficiencies (alloimmune states) or they are acquired in previously unaffected individuals (autoimmune states).
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