Describe the treatment options

Describe the treatment options.

Hemophilia A is treated by replacement therapy with factor VIII. The infusion of 1 U of factor VIII per kilogram of body weight increases the plasma level by 0.02 U/mL. Mild bleeding episodes can be controlled by a level of 0.3 U/mL, whereas severe bleeding requires 0.5 U/mL for control. Normal plasma levels must be maintained during major surgery or life-threatening bleeding. This can be accomplished either by the administration of repeated doses of factor or by continuous infusion. The half-life of factor VIII in the plasma is approximately 8 hours.

The process of obtaining, concentrating and purifying factor VIII has occurred over the past 30 years. Until plasma cryoprecipitate was discovered in 1964, frozen plasma was the only source of factor VIII available. Elective surgery was thus not feasible due to the large volumes of plasma that would be needed. Currently, highly purified factor VIII concentrates are available which provide rapid reversal or prevention of bleeding. Many patients lead nearly normal life-styles with home treatment or even self-treatment.

In the early 1990s, two preparations of recombinant fac-tor VIII were licensed. Clinical studies have confirmed excellent efficacy and a high correlation between the dose given and the resultant plasma level. This recombinant therapy is not associated with antibody formation or transmission of blood-borne diseases such as human immunodeficiency virus (HIV). It is, however, 2–3 times more expensive than plasma-derived factor, and its avail-ability can be limited by production capacity. In the United States, approximately 60% of severe hemophiliacs use recombinant factor VIII.

One drawback to the use of recombinant factor VIII is its formulation with human albumin and other animal proteins. Several new preparations are in clinical trials and are made without human albumin and other antigenic foreign proteins.

A newly approved product, recombinant activated factor VII, has been licensed in the United States and is intended for home use in patients with inhibitors. This agent provides hemostasis by binding directly or in com-plex with tissue factors to negatively charged phospho-lipids exposed on the surface of activated platelets. Recombinant activated factor VIII stops spontaneous and surgically induced bleeding in 70–75% of patients with inhibitors.

Desmopressin (1-deamino-8D arginine vasopressin or DDAVP) can be used to treat mild to moderate hemophilia A. An intravenous dose of 0.3 μg/kg can increase the factor VIII level 3–5 times above baseline. Nasal DDAVP allows for home use.

Hemophilia A as a genetic disease lends itself well to the development of gene therapy since it is caused by the lack of a single gene product. Also, this product is needed in only minute amounts in the plasma. Gene therapy trials are cur-rently under way and offer a future “cure” for all patients with hemophilia A.