Hemophilia B
Hemophilia B (Factor IX deficiency, Christmas disease) causes a prolonged aPTT in the presence of a normal protime. Severity of disease is classified according to the Factor IX level. Patients with Factor IX levels <1% are classified as severe, 1-5% as moderate and 6-60% as mild hemophilia B.
Treatment Guidelines
The treatment of choice for Factor IX deficiency is recombinant Factor IX. A specimen for Factor IX level should be drawn before the loading dose to determine the baseline level, 1 hour after the dose to determine the peak level, and immediately before the next dose to determine the trough level. Caution must be exercised in calculating the dosage of recombinant Factor IX. For example, BeneFIX has lower recovery values than plasma derived Factor IX concentrate due to differences in the post-translational modification of the final protein. In some cases the observed rise in Factor IX level may only be 50% of the expected value. Therefore, higher doses of BeneFIX may be required. The BeneFIX package insert recommends the following dosage calculation:
#Factor IX units required = Body weight (kg) X desired Factor IX increase (%) X 1.2
However, because of the wide variation in recovery between individuals a factor greater than 1.2 may be necessary.
When bleeding is severe, the appropriate dose of Factor IX is 100-120 units/kg, which should result in a factor IX level of 80-100%. General dosage guidelines are summarized in the following table.
Factor IX Dosing Recommendations
|
Bleeding Site |
Loading Dose Units/Kg |
Desired Plasma FVIII Level % |
Maintenance Dose Units/Kg |
|
Oral mucosa |
50 |
30-50 |
Usually not required |
|
Epistaxis |
80-100 |
80-100 initial, then 30 |
70-80 qod |
|
Joint |
30-40 |
30-50 |
30-40 qod as needed |
|
Muscle |
40-60 |
>50 |
40-60 qod |
|
CNS |
100 |
100 initial, then 50-100 |
50 q 24 hours |
|
Gastrointestinal |
80-100 |
100 initial, then 30 |
70-80 qod |
|
Genitourinary |
80-100 |
100 initial, then 30 |
70-80 qod |
|
Major trauma |
100 |
100 initial, then 50 |
100 q 24 hours |
|
Surgery prophylaxis |
50 |
100 initial, then 50 |
100 q 24 hours |
Factor IX Inhibitors
Inhibitors develop in only 1 to 4% of persons with hemophilia B. Approximately 40% have titers less than 5 BU, while the majority has higher titers. Patients with low titers (< 10 Bethesda units) can be treated with sufficient quantities of Factor IX concentrate to overwhelm the inhibitor. Some patients with inhibitors to Factor IX have severe allergic reactions when treated with any plasma product containing Factor IX. Recombinant Factor VIIa is recommended for these patients and for any patient with a high titer inhibitor. The recommended dose is 90 ?g/kg by IV bolus given every two hours until hemostasis is achieved. For severe bleeds, dosing should be continued at 3 to 6 hour intervals to maintain hemostasis.
