Fresh frozen plasma or the supernatant from cryoprecipitated plasma can be used as a source of factor IX replacement. However, plasma therapy is limited by the volumes that must be administered, since each milliliter contains only 1 U factor IX activity. It is difficult to achieve increments in factor IX activity >10–15% of normal with plasma alone. Thus, plasma therapy is not generally recommended since highly purified preparations free of transmissible viruses are now available. In the absence of factor IX concentrates, however, adult patients can tolerate a loading dose of plasma of about 20 ml/kg body weight, followed by 3–6 ml plasma/kg body weight every 8–12 hours. The use of purified factor IX preparations in all hemophilia B patients without inhibitors is now the treatment of choice.
Factor IX Concentrates
When factor IX levels higher than can be achieved with plasma are needed, factor IX concentrates are used. MLID66003705 MLID69109123 MLID93206143 30–33 Until recently, pure preparations of factor IX were not available, and crude preparations referred to as prothrombin complex concentrates (PCCs) were used. PCCs are obtained from DEAE Sephadex adsorption of the supernatant from cryoprecipitated plasma and contain variable quantities of factors VII, IX, and X, prothrombin, protein C, and protein S. The purity of these products is in the range of 1–5 U factor IX activity/mg protein. MLID93206143 33 The presence of these other factors allows the use of these preparations as replacement therapy for other factor deficiencies (see Ch. 110). Table 108-2 Table 108-2 describes selected PCCs containing factor IX. These products are now considered safe in regard to human immunodeficiency virus (HIV) and hepatitis virus transmission.
Despite their utility, PCCs have been less than ideal therapy for hemophilia B due to the presence of clotting factors other than factor IX, which are unnecessary for the treatment of hemophilia B and may contribute to the risk of thromboembolic phenomena (e.g., deep venous thrombosis, disseminated intravascular coagulation [DIC]), which have been associated with use of these products. For this reason, dosing with crude preparations to raise factor IX activity to >50% of normal has been recommended only with great caution. Recently, highly purified factor IX concentrates have become available, allowing safer and more liberal therapy. Purified factor IX is prepared by improved chromatographic procedures that allow better separation of factor IX from the other clotting factors. The purity of the factor IX obtained is 2 orders of magnitude higher than with the crude preparations and contains 50–200 U factor IX/mg protein. Multiple studies have documented the clinical efficacy, lack of thrombogenicity, and viral safety of the purified preparations. MLID93206143 MLID92119275 MLID91246863 MLID92303539 MLID91091494 33–37 The decreased risk of thrombosis permits dosing to 100% activity. The currently available purified factor IX preparations are listed in Table 108-2 Table 108-2, and they are now the treatment of choice for hemophilia B patients.
Current approach to therapy for Hemophilia B
The use of prophylactic therapy should now be strongly considered for new severely affected patients with hemophilia B. Twice weekly dosing with 25–40 U/ kg highly purified factor IX should prevent spontaneous bleeding and the development of chronic joint disease. If prophylactic therapy is not possible, prompt “on demand” therapy should be available. When life-threaten ing hemorrhage is suspected, such as in the central nervous system or near the airway, factor IX should be administered immediately before any diagnostic procedures are performed. Antifibrinolytic agents are helpful in preventing bleeding following dental procedures, but are not recommended for treatment of other hemorrhagic events in patients without inhibitors. These agents are contraindicated in the treatment of hematuria due to the risk of ureteral obstruction.
Most hemarthroses can be treated with one or two doses of factor IX with a goal of reaching plasma factor IX levels of about 25–30% of normal. Typically this involves the administration of about 30 U factor IX/kg body weight. The same dose may be repeated, if needed, at 24-hour intervals. Similar doses are given for superficial and small hematomas. Should hematomas appear to be dissecting at the time of diagnosis, factor IX should be administered until the dissection ceases and resolution of the hematoma begins.
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