THE ROLE OF LOW-DOSE PROPHYLAXIS WITH FACTOR VIII IN THE PREVENTION OF JOINT DAMAGE

Patients with hemophilia are at risk for developing reduced bone mineral density (BMD) due to recurrent hemarthrosis, immobilization, lack of adequate exercise, and low vitamin D levels.

To avoid osteoporosis and its complications, such as pathological fractures, it is necessary to take preventive measures during childhood while the body is growing.

Recently, it has been suggested that a low level of factor VIII may disrupt bone homeostasis creating a pro-inflammatory environment with increased osteoclastic (i.e., of bone-digesting cells) activity and bone erosion. Vitamin D deficiency exacerbates this inflammatory state that alters bone homeostasis resulting in further reduction in bone mineral density.

All this leads to increased rates of fracture, bone pain and reduced quality of life.

Prophylactic treatment with factor VIII for patients with severe hemophilia is adopted as the primary treatment strategy in several countries around the world. It has been shown that early prophylactic treatment can prevent bleeding and arthropathy. Patients with severe hemophilia who do not receive prophylaxis usually have 30-35 joint bleeds a year and are at high risk of developing severe arthropathy.

A recent study of 50 patients with severe hemophilia A aged between 6 and 16 years showed that low-dose prophylaxis in severe hemophilia preserves BMD, increases vitamin D levels, and improves the Hemophilia Joint Health Score (the value that indicates the level of joint health in people with hemophilia).

In addition, the study indicates that these patients have significantly lower levels of vitamin D than healthy controls. Therefore, vitamin D deficiency should be tested in all people with hemophilia for early detection and treatment.

Vitamin D levels are particularly important for the bone health of patients with hemophilia. Vitamin D plays an important role in regulating calcium and bone homeostasis and has effects on the immune and cardiovascular systems. Common manifestations of vitamin D deficiency are symmetrical back pain, muscle weakness, muscle aches, throbbing pain caused by pressure on the sternum and tibia, bone deformity, anxiety, and depression. In children, bones soften over time and become deformed, leading to growth retardation, enlarged epiphyses of the long bones, and leg deformities. Vitamin D deficiency is therefore particularly important for the bone health of individuals with hemophilia, particularly children with severe hemophilia.

 

References

Gamal Andrawes N, Hashem Fayek M, Salah El-Din N, Atef Mostafa R. Effect of low-dose factor VIII prophylaxis therapy on bone mineral density and 25(OH) vitamin D level in children with severe haemophilia A. Haemophilia. 2020 Mar;26(2):325-332. doi: 10.1111/hae.13917.

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Wikiphilia

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

A pathological process consisting in a decrease in the amount of minerals (calcium, magnesium, phosphorus, etc.) contained in bone tissue. This mineral depletion weakens the bone and leads to a consequent increase in the risk of fractures.

The amount of minerals present in a square centimetre of bone.

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.

Product containing a high concentration of freeze-dried factor VIII, used for replacement therapy in the treatment of haemophilia A.

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).

Process that prevents uncontrolled bleeding following damage to a blood vessel.

It consists of 3 main steps: reactive vasoconstriction, during which the damaged blood vessel contracts to temporarily reduce the blood flow to the area where the damage occurred; clot formation, which involves factor VIII; and, lastly, repair system inactivation, in order to definitively repair the damage to the blood vessel wall.

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%.

Bone cells able to produce new bone tissue through the excretion of extracellular matrix.

The cells that cause the break-down (resorption) of bone tissue.

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

Treatment regimen usually used in patients with severe haemophilia A.

It involves the constant, regular administration of the lacking factor VIII, in order to prevent bleeds.

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