| Table 2: Management of bleeding episodes in patients with hemophilia A and B using clotting-factor replacement therapy | ||
| Recommended dosage of replacement factor
(and desired level of clotting-factor activity* to be achieved) | ||
| Indication | Factor VIII+ (hemophilia A) | Factor IX+ (hemophilia B) |
| Mild hemorrhage
Early joint or muscle bleed
| 10-15 U/kg (20%-30%) | 20-30 U/kg (20%-30%) |
| Major hemorrhage
Advanced joint or muscle bleed
| 20-25 U/kg (40%-50%) | 40-50 U/kg (40%-50%) |
| Life-threatening hemorrhage~
Intracranial bleed
|
35-50 U/kg (70%-100%) | 70-100 U/kg (70%-100%) |
| Dental extraction|| | 20-25 U/kg (40%-50%) | 40-50 U/kg (40%-50%) |
*1 U/ml (100% activity) is the clotting-factor activity present in 1 ml of average normal plasma.
+Clotting factor recovery and half-life is as follows. Factor VIII: 1 U/kg produces a rise in plasma titre by approximately 0.02 U/mL (2% activity); half-life is 8-12 h. Factor IX: 1 U/kg produces a rise in plasma titre by appproximately 0.01 U/mL (1% activity); half-life is 18-24 h.
~For life-threatening hemorrhage, maintenance treatment with half the initial dose (every 8-12 h for Factor VIII and every 12-24 for Factor IX) for 5 d to several weeks may be required. Alternatively, recombinant or ultra-high purity Factor VIII and high purity Factor IX can be given by continuous infusion (2 U/kg per hour for Factor VIII, 4 U/kg per hour for Factor IX, with subsequent dosages adjusted according to the plasma clotting-factor levels) following the initial bolus.[40-43]
§If prothrombin-complex concentrate is used, 50-60 U/kg (50%-60% activity) at intervals of 12 h or longer should be given.
||For dental extraction, epsilon-aminocaproic acid (Amicar), 75 mg/kg (up to 4 g) every 6 h, or tranexamic acid (Cykokapron), 25 mg/kg every 6-8 h for 5-10 d, should be given in addition to the clotting factor.[36-68] For patients with hemophelia B receiving prothrombin-complex concentrates, the systemic use of antifibrinolytic agents may potentiate the thrombogenic effects of prothrombin complex concentrates. Amicar or Cyklokapron mouthwash (e.g., 10 mL of 5% Cyklokapron acid rinse four times daily for 7-10 d) can also be used for oral or dental bleeding.[37,38] More recent studies suggest that dental extraction can be safely performed with the plasma clotting-factor level as low as 10% if both oral and local antifibrinolytic agents are also given for 7-10 d.[38]