Prevention and Management of Bleeding Episodes in Children with Hemophilia

Abstract

Regular prophylactic treatment with factor VIII (FVIII) and factor IX (FIX) concentrates in hemophilia A and B, respectively, is introduced in early infancy and has resulted in dramatic improvement of the conditions. Recombinant FVIII and FIX concentrates have been available for > 25 years and have been modified and refined through the years; however, unfortunately frequent intravenous administrations are still necessary. The half-lives of these products have now been extended (EHL) by fusion with albumin, the Fc-portion of IgG, or by being PEGylated. This has been very successful for EHL-FIX, with 3–5 times longer half-life, and to a lesser degree for EHL-FVIII with a half-life extension of only 1.5 times the conventional products. New treatment principles using FVIII mimetics or monoclonal antibodies that rebalance the pro- and anti-coagulation system by interfering with production of anti-thrombin or tissue factor pathway inhibitor have the benefits of long-lasting activity, subcutaneous administration, and being useful in patients both with and without neutralizing antibodies. As the ultimate treatment, recent progress has also been made with gene therapy of both hemophilia A and B.

Burden on parents of children with haemophilia: The impact of sociodemographic and child's medical condition

“…In Sweden, prophylactic treatment with clotting factor for children with severe haemophilia starts when the child is around 12 months of age. The goal is to start prophylactic treatment before the onset of any joint bleeding (Berntorp et al, ; Ljung, ). A child with moderate haemophilia can either be on prophylactic treatment or be treated on demand (Berntorp et al, ).…”

“…The parents are themselves deeply involved in the child's advanced treatment. The prophylactic treatment starts when the child is young, and the clotting factor is administrated intravenously at home, by the parents (Ljung, ; Stoffman et al, ). Studies investigating the perceived burden among parents to children with severe or moderate haemophilia are sparse, and there is a need for increasing knowledge and understanding of the parents’ life situation to further develop and assure quality of care.…”

“…Treatment is based on replacement of the missing clotting factor when a bleed occurs (on‐demand treatment) or regular and continuous treatment (prophylactic treatment). Dose, frequency and type of replacement therapy in haemophilia vary depending not only on the severity of the disease, the child's age and lifestyle, but also on the availability of clotting factor in different countries (Ljung, ). Prophylactic replacement with clotting factor prevents bleeds and is the standard treatment for children with severe haemophilia in high‐income countries (Berntorp & Shapiro, ).…”

Tailoring haemophilia A prophylaxis with BAY 81-8973: A case series

“…One of the most recently approved rFVIII is BAY 81-8973 (Kovaltry ® , Bayer, Berkley, CA, USA), which represents the evolution of Bayer's well-established rFVIII-FS (Kogenate ® FS, Bayer, Berkley, CA, USA) [2,5,7,[13][14][15][16][17][18][19][20]. Despite being produced in the same baby hamster cells, compared with its predecessor rFVIII-FS, BAY 81-8973 is produced by modernized manufacturing technologies which eliminate the use of human-and/or animal-derived raw materials from the manufacturing process (third generation replacement FVIII), decreasing the risk for anti-FVIII antibodies (inhibitors) development and yielding a better safety profile [19].…”

“…The prevalence of HA is approximately 1:7,500 males. The severe forms are usually diagnosed during the first year of life due to abnormal subcutaneous hematomas or hemarthroses, which may occur after minor trauma, or spontaneously [2].…”