Introduction
The prevalence of hemophilia, an X-linked heritable coagulopathy, is roughly one in 10,000 people. Hemophilia A, or factor VIII deficiency, accounts for about 80 % of cases and is the most prevalent. About 20 % of patients have hemophilia B or factor IX deficiency. While Von Willebrand disease and other clotting factor deficits are also heritable clotting disorders, they are not typically categorized as "hemophilia." Traditionally, hemophilia has been categorized as "mild," "moderate," or "severe" based on the extent of clotting factor deficiency relative to the normal population.
What Is the Background of Joint Disease and Hemophilia?
Joint disease, which results in a characteristic chronic arthropathy due to repeated bleeding into joints, is a common and crippling complication of severe (and, to a lesser extent, moderate) hemophilia. Age and a higher body mass index are additional risk factors for developing limits in range of motion]. Higher bleeding frequency, inhibitor presence, and recent orthopedic surgeries are also linked to an increased risk of limited range of motion in patients with severe illness. Patients with severe hemophilia had a higher chance of developing a target joint (a joint in which recurrent bleeding has occurred four or more times in the past six months) than patients with moderate or mild hemophilia (33.1 % versus 18.8 % and 5 %, respectively), according to data from the Universal Data Collection (UDC; US national public health surveillance project).
The knees (45 %) are the most often affected joints in patients who do not receive prophylactic treatment; elbows, ankles, shoulders, and wrists follow. This pattern has altered, at least in prophylactic patients, and the ankle joint is now the most prevalent site of bleeding. This could be because patients can engage in higher-impact sports and activities and can be more active thanks to current preventive regimens and at-home treatments; this could make the ankle the most vulnerable joint. When a person has severe hemophilia, hemarthrosis usually manifests for the first time by the time they are two years old. By the time they are 20 years old, hemophilic arthropathy will develop in these people if they are not adequately treated.
Acute bleeding into a joint can cause excruciating pain due to increased pressure in the bone marrow and synovial cavity, and it can also result in avascular osteonecrosis, especially in the femoral head, after a bleed into the hip joint. In addition to causing synovial injury, repeated bleeding also results in chronic synovitis and damage to bone and cartilage. Patients with severe illness will have clinical symptoms by early adolescence, including pain, edema, and restricted range of motion, which will negatively impact their quality of life and health if they do not receive the proper treatment.
What Is the Pathophysiology of Hemophilia and Its Effect on Joint Health?
There are three stages in the development of hemophilic arthritis:
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Acute thrombocytopenia.
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Prolonged synovitis.
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Arthritis, caused by degeneration.
Although the synovium lining a joint can only absorb so much blood after a single hemarthrosis episode, repeated bleeding into the joint produces a level of blood breakdown products that the synovial membrane cannot eliminate. Iron, an essential component of hemoglobin in erythrocytes, is believed to be responsible for the synovium's inflammation. The iron-rich breakdown product hemosiderin is thought to stimulate the induction of genes that cause cellular proliferation, such as mdm2, and the production of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha.
These changes in synovial tissue are the outcome of hemophilic synovitis. In addition to vascularization and hypertrophy, the synovium experiences an increase in the recruitment of inflammatory cells. This hypertrophied and vascular tissue is more prone to become impinged between the joint's articular surfaces, which increases the risk of further hemorrhage that feeds the cycle of inflammation and bleeding. Moreover, the production of inflammatory mediators disrupts the regular upkeep of articular cartilage. It is believed that articular cartilage can sustain damage from direct blood contact and inflammation linked to the synovium. Research has demonstrated that even brief blood exposure can damage long-term cartilage. The pathogenic mechanisms in rheumatoid arthritis are similar to the significant inflammation and synovial enlargement reported in hemophilic arthropathy. In contrast, the gradual deterioration of hyaline cartilage is similar to that seen in osteoarthritis.
What Is the Management of Joint Disease and Hemophilia?
Controlling Bleeding:
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Before the beginning of the degenerative illness, early prevention and treatment of acute joint hemorrhages are necessary for optimal management of the hemophilic joint disease. With replacement clotting factor concentrates, joint hemorrhages can be treated early. For bleeding to cease and recurrence to be prevented, the amount of clotting factor needs to be high enough and sustained for an extended period. Age-based primary prophylaxis: ongoing, long-term treatment beginning at the age of two years and before any clinically noticeable joint hemorrhage (continuous treatment means treating till adulthood for 52 weeks annually, with a minimum of 46 weeks annually).
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Regardless of age, primary prophylaxis based on the initial joint bleed involves ongoing, lifelong treatment initiated before developing a joint injury.
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Continuous long-term therapy that does not fit the requirements for primary prophylaxis is known as secondary prophylaxis.
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Short-term prophylaxis: Prophylactic measures taken both to prevent and treat bleeding.
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The best way to avoid and/or lower the risk of joint bleeding and arthropathy is generally considered prophylaxis with factor concentrates starting at a young age. There is still uncertainty over the best prophylactic dosage, regimen, and timing. Target trough factor levels should be more than 1 % between doses to achieve the most impact. Giving 25 to 50 IU/kg of factor VIII three times a week or every other day or 40 to 100 IU/kg of factor IX two to three times a week is typically sufficient.
Supplementary Supervision:
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Painkillers: Pain from bleeding into the joint may need to be relieved with analgesics. Analgesics, such as compounds containing Aspirin or other non-steroidal anti-inflammatory medicines, can, however, exacerbate bleeding.
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Anti-inflammatory Medication: After the acute hemorrhage phase, one must consider the synovitis that frequently ensues. Chronic synovitis has been treated by intra-articular corticosteroid injection. Systemic corticosteroids have restricted use because of their side effects, although they might be taken into consideration in certain situations of severe inflammatory reactions that don't respond to conventional treatments.
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RICE: Stands for rest, ice, compression, and elevation. It might not be necessary to immobilize patients with mild hemorrhages. RICE may be a helpful supplemental pain management technique for other patients.
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Physical Therapy: A key therapeutic approach for maintaining joint mobility and function, reducing pain and swelling, preserving muscle mass, and averting injury is physiotherapy.
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Surgical Interventions: In patients with severe joint deficits, when conservative therapy has not worked, open surgical techniques are frequently employed. Particularly in patients with severe hemophilia and/or inhibitors, the advantages of surgery must exceed the possible hazards, which include infection, neuropathy, and hemorrhage.
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Synovectomy: It is advised for synovitis that is not excessively hypertrophic or accompanied by substantial cartilage destruction and is not responding to treatment to stop the progression.
Conclusion
Recurrent hamarthrosis and soft-tissue hamatomas can cause severe arthropathy, joint contractures, and pseudo-tumours over time, which can impair quality of life connected to health and cause chronic pain and disability. One of the main goals of treatment for people with haemophilia is to prevent arthopathy, which is the single leading cause of morbidity in these patients. The best method to stop hemarthrosis and the subsequent onset of arthropathy in people with hemophilia is to replace the missing factor with prophylaxis, as long as this treatment is initiated at a young age. If bleeding is seen, the dosage needs to be customized and increased.
