Treatment of hemophilia in developing countries: A journey of a thousand miles

F requent bleeding into muscles and joints occurring spontaneously or after trauma is the hallmark of hemophilia. For persons with severe disease, repetitive bleeding inevitably leads to chronic joint disease and severe disability. The availability of coagulation factor concentrates in the 1970s revolutionized hemophilia therapy, allowing effective treatment of bleeding episodes. At the same time the advent of self-infusion and homebased therapy permitted prompt treatment of hemorrhages, minimizing morbidity and decreasing time lost from school or work [1]. Despite aggressive on-demand infusion treatment, progressive arthritis, and musculoskeletal disability were not completely eliminated [2]. Once early changes of chronic arthropathy occur, even the prophylactic administration of coagulation factor concentrates to prevent further hemorrhage may not be effective in halting progressive joint changes [3]. International experience indicates that when prophylactic administration of clotting factor concentrates is begun early in life, hemorrhages can be prevented, and joint damage can be eliminated [4–6]. The rationale for prophylaxis is based on the fact that patients with hemophilia with moderate or mild disease (plasma factor levels >1%) rarely have chronic joint problems [7]. Prophylactic regimens as implemented in Europe and North America most commonly involve the administration of coagulation factor three times weekly. Recombinant factor or high purity plasmaderived products are generally preferred over factor concentrates of intermediate purity, bringing the cost of prophylaxis for a 50 kg child to approximately $195,000–312,000 per year [6]. Lower purity factor concentrate products offer safe alternatives at considerably lower cost [8]. Unfortunately, even these lower cost products are prohibitively expensive for approximately 70% of the world’s population of persons with hemophilia who live in developing countries where factor concentrates are either unavailable or in extreme short supply [9]. In most of the world’s impoverished countries, persons with severe hemophilia often do not survive to adulthood and most remain under diagnosed and untreated [10]. In these countries, primary health priorities include nutrition, sanitation, prevention of communicable diseases, and provision of basic health services. A rare and expensive disease such as hemophilia has low funding priority [11]. In addition to nonavailability of clotting factor concentrates, other obstacles to hemophilia care in developing countries include inadequate knowledge of hemophilia, lack of laboratories to diagnose the disorder, and lack of a medical infrastructure to provide centers where comprehensive hemophilia treatment would be available [10]. In low-income countries, hemophilia must often be managed with minimal replacement therapy [11]. Under these restrictions, joint damage is inevitable, but maximizing the use of even limited supplies of factor concentrate, together with the use of physiotherapy, orthotics and rehabilitation services, can prevent long-term disability and preserve independence [12]. When hemophilia care competes with other priorities for scarce healthcare dollars, the costeffectiveness of therapy must be demonstrated. Outcome studies that document the impact of comprehensive hemophilia care on functional independence and quality of life can be compelling arguments for improved hemophilia services. In Mexico as in many developing countries, limited availability of factor replacement therapy has required that factor be given only at the time of joint bleeding, with factor usage averaging between 530 and 817 IU/kg/year compared to usual prophylactic protocols utilized in Europe and North America which require an average of 3,900–6,240 IU/kg/year [13]. To evaluate outcome in patients receiving replacement therapy on-demand for bleeding episodes, Tlacuilo-Parra et al. [14] report in this issue of Pediatric Blood & Cancer their use of the Functional Independence Score in Hemophilia (FISH). FISH is a performance-based assessment tool, designed to objectively measure the functional ability of patients with severe hemophilia. Originally developed by Poonnoose et al. [15] in persons with severe hemophilia, the current authors extend the use of FISH to include persons with moderate disease. This measurement tool appears to be reliable, inexpensive, and easily