Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors.

The management of patients with inhibitors is an important challenge in haemophilia care. The lack of randomized controlled trials means that clinical decisions are generally based on subjective opinions, and purchasers' attention is likely to focus on the costs of treatment. In order to assess the current management of inhibitor patients and use of immune tolerance induction therapy (ITI) in Europe, we performed a survey within a European network of 21 comprehensive care centres from 14 countries (the European Haemophilia Therapy Standardisation Board). The survey identified a total of 381 patients with inhibitors attending the centres, 211 (55.4%) of whom had never been exposed to ITI. Between 1998 and 2003, the centres performed 233 procedures and 114 (48.9%) were successful. The survey demonstrated that dosing, which is the time to start and stop the ITI, the type of concentrate to use and the definition of success varied among the centres. Well-designed trials are warranted to guide decision-making, but in the absence of these studies we have developed consensus guidance for the management of inhibitor patients based on current clinical practice, as identified by the survey, and review of the literature.

Articular cartilage is more susceptible to blood induced damage at young than at old age.

OBJECTIVE: It has been shown that cartilage is damaged upon intraarticular hemorrhage. We investigated differences in the susceptibility of cartilage from young adult and old animals to blood induced joint damage in a canine in vivo model. METHODS: Right knees of 6 young adult beagles (aged 2.2 +/- 0.1 yrs) and 6 old beagles (7.4 +/- 0.3 yrs) were intraarticularly injected twice in 4 days with autologous blood. Dogs were killed 4 or 16 days after the first injection and cartilage matrix proteoglycan content and synthesis and collagen damage were determined. RESULTS: Shortly after blood injection (Day 4), proteoglycan synthesis was inhibited and the proteoglycan content of the cartilage was decreased in both groups. However, the degree of the inhibition of proteoglycan synthesis was significantly greater in young adult animals than in old animals. On Day 16 proteoglycan synthesis was increased in both young adult and old cartilage, but more elevated in old cartilage. The proteoglycan content remained decreased in both young adult and old cartilage, but significantly more so in young adult cartilage than in old cartilage. CONCLUSION: Results suggest that intraarticular bleeding influences cartilage metabolism and repair, and that the cartilage of young adult animals is more susceptible to these influences than cartilage of old animals. Differences in the aging of chondrocytes and age related changes in matrix integrity may be involved. Prevention and appropriate treatment of joint bleeding is indicated and this is especially relevant for young adult cartilage.