A number of inflammatory mediators are involved in this process,

A number of inflammatory mediators are involved in this process, and angiogenesis, induced by

growth factors such as vascular endothelial growth factor is key to the development of synovitis and resultant joint damage. Of interest, there is evidence from in-vitro studies to suggest that immature articular cartilage may be more susceptible to blood induced damage than mature articular cartilage [15]. An understanding of the consequences of acute bleeding into joints may be very important in the design of optimal prophylaxis regimens. Based on the results of experimental studies of blood induced joint damage [11,12,14], C646 concentration it is possible that enhanced episodic therapy for breakthrough bleeding in young boys with severe haemophilia started on primary prophylaxis regimens, as given in the US Joint Outcome Study and the Canadian dose-escalation primary prophylaxis study may be important with respect to preventing subclinical or overt joint bleeding (i.e., rebleeding) following an acute joint bleed [7,16]. This possibility is supported by studies that demonstrate that wound healing is abnormal in mice this website with haemophilia B and suggests that ongoing

coagulation function needs to be maintained to limit bleeding into granulation tissue during tissue remodelling [17]. It is possible that the ‘inflammatory storm’ and stimulation of new blood vessel formation (angiogenesis) that occurs as a result of acute bleeding into a joint may act as a risk factor for subclinical bleeding and rebleeding into the affected joint. Adequate clotting factor cover during this immediate ‘at-risk’ period following an acute joint haemorrhage may therefore be important in ensuring an optimal long-term musculoskeletal outcome. The field of prophylaxis owes a great debt to the

pioneering studies of Professor Inga Marie Nilsson and her colleagues from Malmö, Sweden and Professor van Creveld and his co-workers in Utrecht, the Netherlands. 上海皓元医药股份有限公司 These two groups began programmes of prophylaxis in boys with severe haemophilia in the late 1950’s/1960’s, the results of which have been reported after more than two decades of careful follow-up [18–21]. In both haemophilia treatment centres, prophylaxis was started in boys with a history of some joint bleeding (i.e., secondary prophylaxis), but evolved to programmes where factor infusions were given before, or after a very few, clinically reported joint bleeds. The two prophylaxis programmes differed significantly with respect to age at introduction of prophylaxis and intensity of regimen, as described below. In Sweden, prophylaxis was given as high-doses of factor VIII (FVIII) (25–40 IU kg−1) on alternate days, minimum three times per week for haemophilia A patients and 25–40 IU kg−1 of factor IX (FIX) twice weekly for haemophilia B cases.

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