Clinical Aspects of and Therapy for Hemophilia B. Harold R. Roberts and T, Flint Gray III, страница 4

The level of factor IX activity usually correlates well with the observed clinical severity. In severe hemophilia B patients, the factor IX levels are usually <1% of normal and are associated with frequent "spontaneous" bleeding episodes, so called because the patient can recall no specific trauma. Factor IX levels of 1–5% are usually associated with moderate disease, while levels of >5% are usually predictive of mild hemophilia B. Overlap between these categories is common. Table 108-1 Table 108-1 describes the features of mild, moderate, and severe hemophilia B. Spontaneous bleeding is uncommon with factor IX levels of >25–30% of normal, although excessive bleeding may occur with trauma or surgery. A normal PTT does not alone guarantee levels of factor IX activity sufficient to prevent abnormal surgical bleeding.

Therapy

General Considerations

Replacement therapy is dictated by the location of bleeding and whether it is mild, moderate, or severe. 27 1-Deamino-8-arginine vasopressin (DDAVP) is of no value in hemophilia B. Antifibrinolytic agents such as e-aminocaproic acid and tranexamic acid are useful following dental extractions but are of no value in treating hemarthroses. These agents should never be used to treat hematuria because of the chance of developing ureteral clots with subsequent obstruction and, on occasion, renal failure. MLID87124813  28 Aspirin should be avoided in hemophilia B. The pain of hemophilic arthropathy can be treated with acetaminophen or nonsteroidal anti-inflammatory drugs. The latter may enhance the bleeding tendency; therefore, different ones should be tried in an attempt to find the one best tolerated by the patient. Because of the danger of addiction in patients with frequent painful bleeding episodes, it is wise to avoid using narcotics (codeine, morphine, meperidine) for chronic pain, although the fear of addiction should not deter the physician from using narcotics when appropriate for acute presentations. Narcotic use in hemophilic patients should be closely monitored and the dangers of addiction openly and frankly discussed with the patient (see Ch. 107).

Dosage in Replacement Therapy

One unit of factor IX is defined as the amount of factor IX activity present in 1 ml of pooled normal human plasma and is equivalent to 100% activity. The dose of factor IX needed to achieve a desired level of activity can be calculated based on estimation of the patient's plasma volume and knowledge of factor IX kinetics.

Plasma volume may be estimated as 5% of body weight or 50 ml/kg body weight. Thus the plasma volume of a 70-kg patient is approximately 3,500 ml. By definition, for such a patient to have 100% factor IX activity, 1 U/ml or a total of 3,500 U of factor IX must be present in this plasma volume. If severe hemophilia B is present, it may be assumed the initial factor IX activity is zero. Thus, to obtain 100% activity E3,500 U of factor IX must be administered. Because of rapid redistribution into the extravascular space and adsorption onto endothelial cells of vessel walls, however, only about 50% of the infused factor IX remains in circulation after a short period. In this hypothetical patient, therefore, the initial dose to obtain 100% activity must be 7,000 U. To generalize to any size patient with any initial factor IX level and any desired target level, infusion of 1 U/kg body weight of factor IX will raise the factor IX level approximately 1%. For example, a dose of 1,750 U would raise a 50-kg patient from a starting factor IX level of 15% to a target of 50% activity.

After its initial rapid redistribution, factor IX has a second phase half-life of approximately 18–24 hours. MLID81256015  29 Because the variability in this measurement is significant, it is best determined in each individual patient to allow proper dosing. Based on these data, the factor IX level of a patient raised to 100% activity would be expected to decay to 50% by approximately 24 hours after infusion of the initial dose. A second bolus one-half the amount of the first should then raise the level from 50% to 100% factor IX activity. Factor IX is commonly administered in boluses every 12–24 hours. Figure 108-2 illustrates the kinetics of factor IX decay. It is generally recommended that factor IX levels be monitored after the initial bolus and then daily (initially with peak and trough measurements) to allow individual adjustment in dosing in the treatment of significant bleeding, or in surgical patients. The use of a constant infusion of factor IX to maintain a steady-state level, as has been done with factor VIII concentrates, has not been reported with the recently available highly purified factor IX preparations. Constant infusion of crude factor IX concentrates is not recommended.