Pediatric Clinics of North America - CIPERJ

358 RODRIGUEZ & HOOTS
Fig. 1. X-linked recessive inheritance of hemophilia. Asterisk (*) designates affected chromosome.
(From Pruthi RK. Hemophilia: a practical approach to genetic testing. Mayo Clin
Proc 2005;80(11):1485–99; with permission.)
media or in the final stabilized product (Table 1) [1]. Treatment of patients
who develop inhibitors against factor VIII or IX is significantly more challenging
than treatment of patients who do not have such antibodies. For
patients who have high-titer inhibitors, the use of bypassing agents, such
as recombinant factor VIIa or activated prothrombin complex concentrates,
may be necessary to achieve hemostasis. In these particular patients, however,
the ultimate therapeutic goal is to eradicate the inhibitor by means
of immune tolerance induction (ITI). With this approach, patients receive
repetitive doses of factor VIII or IX, usually once a day, with or without associated
immunosuppresion. Typically, there is an initial rise in the antibody
titers as a result of anamnestic response. Subsequently, however, a gradual
reduction in titer is seen until in the end the inhibitor becomes undetectable.
After successful immune tolerance, patients continue on regular factor infusions
several times per week.
This article focuses on recent advances. From a clinical standpoint, different
prophylactic regimens, including primary, secondary, and tailored prophylaxis,
for severe hemophilia are discussed. Some of these regimens may
serve as alternatives to primary prophylaxis in developing countries where
the high cost of factor concentrates precludes its regular use. Adjuvant treatment
options for bleeding management in hemophilia also are discussed
along with the role of radionuclide synovectomy with isotopes, such as
phosphorus 32 sulfur colloid (P 32 ) to treat joint arthropathy. Current challenges
in hemophilia care, including inhibitor development and approaches
to achieve ITI, are addressed.
From a research standpoint, some of the mechanisms believed to lead to
blood-induced joint disease are discussed. Data suggest that iron deposition