Management of Hemophilia

The treatment of hemophilia may involve management of hemostasis,

management of bleeding episodes, use of factor replacement products and
medications, treatment of patients with factor inhibitors, and treatment and
rehabilitation of patients with hemophilia synovitis.
Treatment of patients with hemophilia ideally should be provided through a
comprehensive hemophilia care center. These centers follow a
multidisciplinary approach, with specialists in hematology, orthopedics,
dentistry, and surgery; nurses; physiotherapists; social workers; and related
allied health professionals. Patients treated at comprehensive care clinics
have been shown to have better access to care, less morbidity, and better
overall outcome.
Ambulatory replacement therapy for bleeding episodes is essential for
preventing chronic arthropathy and deformities. Home treatment and infusion
by the family or patient is possible in most cases. Prompt and appropriate
treatment of hemorrhage is important to prevent long-term complications and
disability.
Dose calculations are directed toward achieving a factor IX (FIX) activity level
of 30% for most mild hemorrhages, of at least 50% for severe bleeds (eg,
from trauma) or for prophylaxis of major dental surgery or major surgery, and
80-100% in life-threatening hemorrhage. Hospitalization is reserved for severe
or life-threatening bleeds, such as large soft tissue bleeds; retroperitoneal
hemorrhage; and hemorrhage related to head injury, surgery, or dental work.
Patients are treated with prophylaxis or intermittent, on-demand therapy for
bleeding events. Prophylaxis has been shown in many studies to prevent or at
least reduce the progression of damage to target sites, such as
joints. [6, 7] According to a review of six randomized controlled trials,
preventative therapy started early in childhood, as compared to on-demand
treatment, is able to reduce total bleeds and bleeding into joints resulting in a

decrease in overall joint deterioration and an improvement in patient quality of

life. [8]
In most developed countries with access to recombinant product, prophylaxis
is primary (ie, therapy is started in patients as young as 1 y and continues into
adolescence). A cost-benefit analysis indicates that this approach reduces
overall factor use and significantly reduces morbidity. [9]
In situations in which this is not feasible, secondary prophylaxis (ie, therapy
after a target joint has been established to prevent worsening of the joint) is
instituted for a defined period. [10, 11] Dosing is designed to maintain trough
levels greater than 2%. This usually requires the administration of FIX 2 times
per week. Individualized therapy (ie, tailored prophylaxis) has been also used
with success; the best approach has yet to be determined.
In the future, the development of FIX preparations with extended half-lives
may permit less-frequent dosing of FIX; in a mouse model, a molecularly
engineered FIX molecule maintained protection against bleeding
approximately three times longer, compared with recombinant FIX. [12] Oral
administration of FIX for prophylaxis may become possible, through the use of
hydrogel carriers that protect FIX from destruction in the stomach and release
it in the intestines. [13] Gene therapy offers the potential for a definitive cure,
and has shown promise in small trials in humans. [14]