Consequences of intra-articular bleeding in haemophilia: science to clinical practice and beyond

Summary. Blood in the joint causes a number ofphysiological and pathological events that eventuallylead to haemophilic arthropathy. Animal models showthat blood in the joint induces inflammation thatcontinues long after blood has been cleared [1]. TNF-alpha, IL-1beta and IL-6 are inflammatory mediatorsthat increase following haemarthrosis in haemophilicmice [2]. Conventional anti-inflammatory drugs havefailed to demonstrate a lasting effect in preventinghaemophilic arthropathy. A new TNF-alpha antagonisthas shown promising results in haemophilic mice [3].Similarly, the use of cyclo-oxygenase-2 inhibitors mayreduce angiogenesis associated with the healing processfollowing bleeding and the associated tissue damage [4].Animal models are useful for studying the pathophys-iology of haemarthropathy, however, when applyingresults from animals to humans, the differences inmatrix turnover rate, thickness of cartilage and jointbiomechanics must be kept in mind [5]. In people withhaemophilia, there is a variable response to haemarth-rosis as demonstrated by magnetic resonance imaging(MRI). Up to 30% of subjects have normal MRI despitehaving three or more haemarthroses into the same joint[6]. Once bone damage is present, little can be done torestore anatomic integrity. Several molecules, includingmembers of the bone morphogenic protein subfamily,have been injected into bone defects in non-haemophil-ic subjects with some evidence of benefit [7]. To achievethe primary goal of reducing blood in the joint and thenegative sequelae, it is questionable to use ice to treathaemarthrosis. Indeed low temperature is associatedwith impairment of coagulation enzyme activity andplatelet function [8].Keywords: angiogenesis, cartilage, haemophilia, hemarth-rosis, hemarthropathy, inflammation, synovitis