Managing Hemophilia in Children and Adolescents

Hemophilia is an X-linked recessive bleeding disorder caused by deficiency of FVIII (hemophilia A) or FIX (hemophilia B). Mutations in the FVIII or FIX genes, both located on the long arm of the X chromosome, are detectable in the majority of cases of hemophilia A or B, respectively. During normal hemostasis, FVIII and FIX form an enzymatic complex; thus, deficiency of either protein leads to a clinically similar phenotype, although there is some evidence to suggest that in the context of severe factor deficiency hemophilia B may be a subtly milder disorder than hemophilia A [1]. In contrast, deficiency of FXI (previously termed ‘hemophilia C’) is genetically and clinically distinct, and is discussed further in chapter 8. Similarly, ‘acquired hemophilia’ is a pathogenically unrelated autoimmune disorder, the management of which is discussed in chapter 9. Hemophilia occurs in all racial groups with an estimated incidence of around 1/5,000 males for hemophilia A, and 1/30,000 for hemophilia B. As these are X-linked disorders, almost all severely affected individuals are male. The factor levels of heterozygous females are on average approximately half those of the normal population; however, females may be more severely affected through one of a variety of mechanisms (e.g. skewed X-inactivation, homozygosity, or chromosomal abnormalities such as Turner syndrome). Females with factor levels in the deficient range should be regarded as having hemophilia, as the approach to management is similar to that for males with corresponding levels of factor deficiency. The clinical phenotype in hemophilia, although highly variable, is traditionally classifi ed according to the baseline factor level (table 1). Affected individuals have a lifelong bleeding tendency that may manifest with spontaneous bleeding, particularly into joints and muscles of a severely affected individual, or as prolonged bleeding after surgery or trauma. Repeated bleeding into joints, the hallmark of severe hemophilia, results in chronic synovitis with destruction of bone and cartilage, ultimately leading to crippling