Little data are, however,

mTOR inhibitor available regarding the optimal management of acute haemarthrosis, especially with respect to replacement therapy and the use of adjunctive therapies (aspiration, avoidance of weight bearing and immobilization, as well as the use of anti-inflammatory medication and embolization). To provide more insight into the management of acute haemarthrosis in patients with haemophilia, a literature review was conducted. Concomitantly, current management was surveyed in 26 European haemophilia comprehensive care centres representing 15 different countries. The review highlights the need for future robust studies to better define the appropriate replacement therapy and the role of adjunctive therapies such as aspiration. The survey reveals much heterogeneity in the management of acute haemarthrosis across the EU. Within the constraints discussed, treatment recommendations are presented that reflect the literature, current practice and the clinical experience of the European Haemophilia Therapy Standardisation Board (EHTSB). Acute haemarthrosis is one of the most frequent types Talazoparib manufacturer of bleeding in individuals with haemophilia. Very young persons, not yet treated with prophylactic infusions of factor concentrate, and subjects treated on demand are at risk of developing acute haemarthrosis. In addition, although prophylactic treatment significantly reduces the

incidence, it does not totally abolish the risk of acute haemarthrosis [1]. The key event in the development 上海皓元医药股份有限公司 of haemophilic arthropathy is the extravasation of blood into the joint [2,3]. Although the precise mechanisms are still incompletely understood,

in vitro and in vivo animal studies demonstrate that deposition of iron in the synovium causes a marked inflammatory response, which in turn leads to damage to cartilage. Iron initiates synovial cell proliferation, and it has been hypothesized that it may act through the induction of critical genes including c-myc and mdm2 that control synovial cell proliferation and apoptosis respectively [4]. These synovial changes indirectly damage and destroy cartilage, but more recent data have shown that cartilage may be directly and independently affected by haemarthrosis. Biochemical markers of chondrocyte damage, such as impaired proteoglycan synthesis, may be seen after relatively short exposure to blood [3,5,6]. Inflammatory mediators such as IL-1α and TNF-α, released from monocytes/macrophages, are also important in synovitis and cartilage destruction, while recent experimental data demonstrate an apparent role for IL-10 in protecting joints from cytokine-mediated damage. Angiogenesis caused by VEGF release may also exacerbate synovitis [2,4]. Additionally, physical factors such as joint loading may act synergistically to cause long-term joint damage after joint bleeds [7].