Dosage
GENERAL APPROACH TO TREATMENT AND ASSESSMENT OF TREATMENT EFFICACY
The dosages described below are presented as general guidance. It should be emphasized that the dosage of Kogenate FS required for hemostasis must be individualized according to the needs of the patient, the severity of the deficiency, the severity of the hemorrhage, the presence of inhibitors, and the FVIII level desired. It is often critical to follow the course of therapy with FVIII level assays. The clinical effect of FVIII is the most important element in evaluating the effectiveness of treatment. It may be necessary to administer more FVIII than estimated in order to attain satisfactory clinical results. If the calculated dose fails to attain the expected FVIII levels, or if bleeding is not controlled after administration of the calculated dosage, the presence of a circulating inhibitor in the patient should be suspected. Its presence should be substantiated and the inhibitor level quantitated by appropriate laboratory tests. When an inhibitor is present, the dosage requirement for FVIII could be extremely variable among different patients, and the optimal treatment can be determined only by the clinical response.
Some patients with low-titer inhibitors (<10 BU) can be successfully treated with FVIII preparations without a resultant anamnestic rise in inhibitor titer.1 FVIII levels and clinical response to treatment must be assessed to insure adequate response. Use of alternative treatment products, such as Factor IX Complex concentrates, Antihemophilic Factor (Porcine), recombinant Factor VIIa or Anti-Inhibitor Coagulant Complex, may be necessary for patients with anamnestic responses to FVIII treatment and/or high-titer inhibitors.
Calculation of Dosage
The in vivo percent elevation in FVIII level can be estimated by multiplying the dose of Kogenate® FS Antihemophilic Factor (Recombinant) per kilogram of body weight (IU/kg) by 2% per IU per kg. This method of calculation is based on clinical findings with the use of plasma-derived and recombinant AHF products and is illustrated in the following examples:
The dosage necessary to achieve hemostasis depends upon the type and severity of the bleeding episode, according to the following general guidelines:
| Minor hemorrhage (superficial, early hemorrhages, hemorrhages into joints) |
20-40% |
10-20 IU per kg
Repeat dose if evidence of further bleeding. |
Moderate to major hemorrhage (hemorrhages into muscles, hemorrhages into the oral cavity, definite hemarthroses, known trauma)
Surgery
(minor surgical procedures) |
30-60% |
15-30 IU per kg
Repeat one dose at 12-24 hours if needed. |
Major to life-threatening hemorrhage (intracranial, intraabdominal or intrathoracic hemorrhages, gastrointestinal bleeding, central nervous system bleeding, bleeding in the retropharyngeal or retroperitoneal spaces, or iliopsoas sheath
Fractures
Head trauma |
80-100% |
Initial dose 40-50 IU per kg
Repeat dose 20-25 IU per kg every 8-12 hours. |
Surgery
Major surgical procedures |
~ 100% |
Preoperative dose 50 IU/kg
Verify ~100% activity prior to surgery. Repeat as necessary after 6 to 12 hours initially, and for 10 to 14 days until healing is complete. |
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1 Kasper CK: Complications of hemophilia A treatment: factor VIII inhibitors. Ann NY Acad Sci 1991; 614:97-105.
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