Hemophilia B patients with high-titer inhibitors may be treated with activated prothrombin complex concentrates such as Autoplex or FEIBA. Although these preparations contain factor IX, its presence in this setting is irrelevant due to the excess of inhibitor; the utility of these products derives from their ability to provide activated clotting factors that "bypass" factor IX. Therefore, monitoring of factor IX activity is not warranted, and the preparations are dosed empirically. Thromboembolic events, including DIC, have been reported with FEIBA and Autoplex. MLID92345426 62 The administration of activated concentrates in the setting of a high-titer inhibitor does not guarantee adequate hemostasis, which is achieved in only 60–80% of cases. For this reason, close monitoring is required in treatment of hemorrhage. Elective surgery should not be performed when patients are using activated PCCs. Table 108-3 Table 108-3 depicts the characteristics of Autoplex and FEIBA. A potentially effective therapy for patients with factor IX inhibitors is recombinant factor VIIa. This factor, administered to dogs with hemophilia B, is effective in stopping bleeding from a standardized bleeding site. MLID93244545 64 Experience in human studies and clinical trials has been encouraging. MLID93244545 MLID91337932 MLID93015524 64–66
The removal or suppression of inhibitors is difficult and expensive and in many affected patients has not been attempted. Temporary removal of inhibitors has been attempted through extracorporeal adsorption methods. The use of immunosuppression and the induction of immune tolerance through prolonged daily factor IX infusion or intravenous immunoglobulin administration, or both, have been investigated. Combinations of these approaches have also been used with varying success. MLID93015524 MLID94054292 MLID93122638 66–68
Surgical procedures can be done safely in hemophilia B patients who are undergoing factor IX replacement therapy, except when high-titer inhibitors are present. MLID92303539 MLID86091472 36,69 Factor IX levels should be raised to 100% of normal with a purified factor IX concentrate before surgery and maintained by infusions of factor IX every 12–24 hours for 7–10 days, depending on the type of surgery.
Prognosis and Future Directions
Before the era of effective therapy for hemophilia B, the life expectancy of a patient was 11 years. 70 When factor IX concentrates became available, life expectancy was dramatically improved despite the ensuing epidemic of hepatitis. The introduction of HIV infection into more than one-half of the patients between 1978 and 1983 has resulted in increased mortality from the acquired immunodeficiency syndrome. However, the availability of concentrates free of HIV and hepatitis viruses holds the promise of a virtually normal life span for new patients and those who have avoided HIV infection. The recent introduction of purified factor IX products has freed hemophilia B patients from the risks of iatrogenic thrombosis and suboptimal treatment present with crude factor IX preparations. Previously untreated patients, or those treated since 1985 may expect a normal life span in the absence of central nervous system bleeding, provided that factor IX concentrates are readily available.
In addition to "on demand," therapy, prophylactic therapy of hemophilia B is now possible. Continued regularly scheduled factor IX infusions once or twice weekly may prevent the development of hemarthroses in very young patients and allow a more active life style with decreased complications in patients of all ages. Although prophylactic therapy is expensive, consideration should be given to the potential savings gained from a decreased complication rate and increased productivity of patients so treated.
The most exciting prospect for treatment of hemophilia B is the possibility of cure through gene therapy. Since the determination of the factor IX gene structure, rapid progress has been made in developing methods to transfer and maintain the gene, first in in vitro cell cultures and more recently directly into animals. MLID89134956 MLID94023934 14,71,72 Refinement of gene transfer techniques may lead to the ability to provide low-cost, safe, prophylactic therapy to hemophilic patients in the future, allowing them to lead a normal life.
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