Spontaneous joint bleeding leading to debilitating arthropathy over time is a major cause of morbidity in patients with hemophilia A. Recurrent joint bleeding induces joint damage in approximately 80% of patients, with knees, elbows, and ankles being the main target joints.
Since the introduction of prophylactic factor VIII replacement therapy in some parts of the world, the annualized bleeding rate in patients with severe hemophilia A has been reduced from 20 to 30 episodes of bleeding a year to only a few episodes. However, despite prophylactic treatment, patients are still not protected from developing arthropathy, suggesting that treatment should effectively eliminate joint bleeding to completely prevent arthropathy.
Some studies have suggested that if the amount of blood that builds up in the joint as a result of a single joint bleed exceeds a certain threshold, it can cause chronic changes. In addition, in-vitro studies have shown that the detrimental effect of blood on cartilage depends on the concentration of the blood. However, although several clinical studies have investigated the relationship between the number of clinically evident joint bleeds and the degree of arthropathy, none of these studies have quantified or described individual bleeds in greater detail. Therefore, it is not known whether the severity of individual joint bleeds is related to the subsequent development of arthropathy. Nonetheless, an important piece of evidence from the studies is that even in the absence of visible acute joint bleeding, joint damage is observed in hemophiliacs. Therefore, it has been hypothesized that this is due to chronic micro-bleeds that cause joint deterioration without clinically evident acute joint bleeds.
Therefore, chronic micro-bleeding in the joints or subchondral bone in young people with hemophilia could cause joint deterioration without clinical evidence of hemarthrosis, and prophylactic treatment prevents this subclinical process. Furthermore, although sporadic subclinical micro-bleeds do not cause direct cartilage degeneration, they contribute to joint degeneration as a result of long-term chronic inflammation.
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