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
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
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.