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

<jats:p><jats:bold>Summary. </jats:bold> Blood in the joint causes a number of physiological and pathological events that eventually lead to haemophilic arthropathy. Animal models show that blood in the joint induces inflammation that continues long after blood has been cleared [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b1">1</jats:ext-link>]. TNF‐alpha, IL‐1beta and IL‐6 are inflammatory mediators that increase following haemarthrosis in haemophilic mice [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b2">2</jats:ext-link>]. Conventional anti‐inflammatory drugs have failed to demonstrate a lasting effect in preventing haemophilic arthropathy. A new TNF‐alpha antagonist has shown promising results in haemophilic mice [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b3">3</jats:ext-link>]. Similarly, the use of cyclo‐oxygenase‐2 inhibitors may reduce angiogenesis associated with the healing process following bleeding and the associated tissue damage [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b4">4</jats:ext-link>]. Animal models are useful for studying the pathophysiology of haemarthropathy, however, when applying results from animals to humans, the differences in matrix turnover rate, thickness of cartilage and joint biomechanics must be kept in mind [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b5">5</jats:ext-link>]. In people with haemophilia, there is a variable response to haemarthrosis as demonstrated by magnetic resonance imaging (MRI). Up to 30% of subjects have normal MRI despite having three or more haemarthroses into the same joint [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b6">6</jats:ext-link>]. Once bone damage is present, little can be done to restore anatomic integrity. Several molecules, including members of the bone morphogenic protein subfamily, have been injected into bone defects in non‐haemophilic subjects with some evidence of benefit [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b7">7</jats:ext-link>]. To achieve the primary goal of reducing blood in the joint and the negative sequelae, it is questionable to use ice to treat haemarthrosis. Indeed low temperature is associated with impairment of coagulation enzyme activity and platelet function [<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#b8">8</jats:ext-link>].</jats:p>