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.



  • Vøls KK, Kjelgaard-Hansen M, Ley CD, Hansen AK, Petersen M. Initial joint bleed volume in a delayed on-demand treatment setup correlates with subsequent synovial changes in hemophilic mice. Animal Model Exp Med. 2020 Jun 3;3(2):160-168. doi: 10.1002/ame2.12118.
  • Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007 Aug 9;357(6):535-44. doi: 10.1056/NEJMoa067659.
  • van Meegeren ME, Roosendaal G, Jansen NW, Lafeber FP, Mastbergen SC. Blood-Induced Joint Damage: The Devastating Effects of Acute Joint Bleeds versus Micro-Bleeds. Cartilage. 2013 Oct;4(4):313-20. doi: 10.1177/1947603513497569.
  • Melchiorre D, Manetti M, Matucci-Cerinic M. Pathophysiology of Hemophilic Arthropathy. J Clin Med. 2017 Jun 25;6(7):63. doi: 10.3390/jcm6070063.
Back to news and insights


Learn more about the meaning of the words you read on this page and learn about the entire glossary on hemophilia.

Fuoriuscita di sangue dai vasi sanguigni che si verifica in seguito al danneggiamento delle loro pareti.

L’emorragia si definisce interna nei casi in cui il sangue defluisce in una cavità naturale del corpo, o esterna quando il sangue si riversa all’esterno o in una cavità comunicante con l’esterno.

A bleed that occurs in a joint, i.e. the point at which two bones meet.

Haemarthroses are the most common bleeding events in patients with haemophilia and cause the swelling and redness of the joint, which becomes warm and painful.

The joint’s prolonged exposure to the inflammation generated by the build-up of blood can lead to the development of joint disease.

A ereditary genetic illness, characterised by a deficiency of clotting factor VIII, that exposes the individual to a greater risk of both internal and external bleeds.

Haemophilia A is more common in males, whereas females tend to be healthy carriers of the condition.

The typical symptoms of the condition include haemarthroses (joint bleeds) and haematomas (muscle bleeds).

Damage that occurs in the joints and prevents their normal function, thereby impairing the individual’s ability to move normally. In haemophiliac patients, joint disease is usually the consequence of recurrent haemarthroses.

Condition that occurs when factor VIII activity is between 1% and 5%.

Condition that occurs when factor VIII activity is between 1% and 5%.

Pathological condition associated with severe bone mineral mass depletion that makes the bones frailer and more prone to fractures.

Condition that occurs when factor VIII activity is <1%.