The following scenarios will discuss how prophylaxis regimens can be implemented to protect the individual from developing spontaneous and activity-induced acute bleeding complications and to maintain an improved quality of life. Since its introduction in 1958 by Professor Nilsson in Sweden , many long-term observational studies [2-5], two paediatric [6, 7] and two adult [8, 9] randomized controlled trials have shown that prophylactic replacement therapy for severe haemophilia
prevents bleeds, and subsequent haemophilic arthropathy. Prophylaxis, initiated before the onset of arthropathy is the recommended treatment for boys with severe haemophilia A and B [10-12]. TGF-beta inhibitor In spite of the high costs of prophylaxis, most countries have followed the successful Swedish prophylactic regimen. This regimen originally aimed at maintaining trough levels of 1–2% clotting factor activity by using doses of 25–40 IU kg−1 three times a week for haemophilia A . In the Netherlands, however, prophylaxis was introduced in 1968 , using lower doses, aiming at preventing spontaneous joint bleeds without targeting on trough levels of factor VIII (FVIII) or FIX. Although treatment was intensified over the years in both countries [3, 14], the difference in dosing has remained considerable: today, a typical adult Dutch haemophilia A patient uses 3 × 1000 IU of FVIII per week, whereas a typical adult Swedish patient
uses 1500–2000 IU every other day. Both groups have followed their patients www.selleckchem.com/products/abt-199.html for decades and reported favourable long-term results. As the optimum regimen is not established and the pressure on healthcare budgets is considerable, the question
arose as to what the incremental gains of high-dose prophylaxis are . An observational study was performed to compare long-term outcomes and costs between the Dutch intermediate-dose and the Swedish high-dose prophylactic regimen in severe haemophilia . All patients with severe haemophilia (FVIII/IX <1% or <1 IU dL−1), born between 1 January 1970 and 1 January 1994, treated at the participating centres, with life-long access to care and treatment data available were eligible for this study. Patients with a history of inhibitors (titres >0.6 BU with decreased recovery) were excluded. Diagnosis and onset of joint bleeding were collected from the files. In addition, Pyruvate dehydrogenase lipoamide kinase isozyme 1 the full history of treatment, including all prophylactic regimens used until evaluation was collected. For the last 5 years before evaluation, annual clotting factor consumption, number of (joint) bleeds, number of visits to the centre, hospital admissions, and days lost from work/school were documented. The primary outcome parameter was clinical joint status, assessed by the centre’s physiotherapist, using the Haemophilia Joint Health Score (HJHS version 1.0) [17, 18]. The HJHS is based on physical examination of elbows, knees, and ankles. The total score ranges from 0, signifying perfect joint health, to 144.