Joint Damge in Hemophilia Patients

Hemophilia is an X-chromosome-linked condition characterized by a lifelong higher risk of hemorrhage due to a deficit or functional abnormality of coagulation factor VIII or IX.                              

 

Hemophilia A affects one out of every 10,000 individuals worldwide, and hemophilia B affects one out of every 25,000 individuals. Hemophilia A and B have comparable clinical symptoms when it comes to joint disorders. The FVIII or FIX coagulant activity is less than 1% of normal in severe hemophilia. Patients with coagulant activity levels between 2 and 5% are usually just minimally affected, and those with levels above 5% have serious trauma difficulties. The lower the clinical difficulties, the higher the FVIII or FIX coagulant activity. Serious bleeding can occur spontaneously in severe hemophilia, which affects 45 percent of patients. This is especially true in the bigger joints. In severe hemophilia, joints account for 85 percent of all bleeding events, with the ankle, knee, and elbow accounting for 80 percent of these; the hip and shoulder are impacted to a lesser amount. There is no satisfactory explanation for why bleeds occur so frequently in joints compared to other places, or why the knee, ankle, and elbow joints are predisposed to bleeding.

Pain, swelling, warmth, and muscular spasm are the direct symptoms or "short-term" repercussions of joint hemorrhage. As the blood is reabsorbed, the lesion settles in a few days with proper therapy. Joint bleeding has more dangerous "long-term" consequences. Repeated episodes of intra-articular bleeding injure the joint, resulting in deformity and crippling (hemophilic arthropathy).

 

Recurrent hemarthrosis causes specific changes in the synovium and cartilage, eventually leading to the joint's entire destruction. Hemophilic arthropathy is the name for this condition. Hemophilic arthropathy is the most common cause of morbidity in hemophilia patients, and it has a significant influence on their quality of life. Because hemophilia patients today have a normal life expectancy, the number of disease years per patient (concerning joint disease) can be as high as 50. When it comes to the therapy of hemophilia's most common consequence, hemophilic arthropathy, unanimity is difficult to come by. The severity of a bleed, the degree of joint injury, and the type of synovitis, for example, are all subject to debate and misinterpretation.

             

Hemophilic arthropathy is characterized by synovial alterations and articular cartilage degradation. Cartilage helps to the exceptional qualities of joints by allowing for the distribution of heavy compressive loads as well as stable joint mobility with minimal friction. There are no reports demonstrating that the cartilage of hemophilia patients differs from that of healthy people before joint deterioration begins. Degenerative joint illnesses, such as osteoarthritis; inflammation-mediated joint diseases, such as rheumatoid arthritis; and blood-induced joint illnesses, such as hemophilic arthropathy, all cause cartilage degradation and synovial tissues.

INFLAMMATORY SYNOVIUM-MEDIATED ASPECTS OF HEMOPHILIC ARTHROPATHY

Synovial and cartilage alterations are thought to be caused by the recurrent extravasation of blood into the joint cavity. Changes in the synovial fluid leads to deterioration of cartilage. Synovial inflammation is thought to be triggered by the gradual accumulation of iron from red blood cells cleared from the joint cavity by synovial macrophages over time during successive intra-articular hemorrhages. This synovial inflammation would eventually result in joint degeneration that would show up years after the initial bleeding incident. The deposition of iron (hemosiderin) in the synovium, both in the synovial lining and the supporting layer, is an important feature of synovial alterations. Hemosiderin deposits appear as distinct granules dispersed throughout the cytoplasm of the cells in the lining. Both intracellular and extracellular hemosiderin deposits emerge as thick clumps in the supporting layer. The synovium appears brownish (hemosiderotic) macroscopically due to an excess of synovial iron deposits. Synoviocyte hypertrophy and neovascularization are considered to be induced by hemosiderin deposits. Another impact of the hemosiderin deposits is lymphocyte infiltration of the synovial membrane, albeit no lymphocyte follicles, as found in the synovial membrane of rheumatoid arthritis, have been identified.

Hypertrophic synovial tissue with hemosiderin depositions can be seen on MRI in joints with persistent synovitis. Synoviorthesis or early synovectomy may slow down joint degradation in hemophilic arthropathy, in addition to reducing the frequency of bleeding episodes.

DEGENERATIVE CARTILAGE MEDIATED ASPECTS OF HEMOPHILIC ARTHROPATHY

Indeed, a large number of findings on blood-induced joint damage imply that synovial alterations play a significant role in the progression of joint damage. Proliferation and inflammation of the synovial tissue are one of the first consequences seen in experimentally generated hemarthrosis (synovitis). Synovial alterations are hypothesized to cause, and so precede, cartilage modifications. However, certain observations raise the question of whether this is the lone and primary cause of joint injury in hemophilia. Others believe that intra-articular blood has a direct damaging effect on cartilage before and independent of synovial alterations, and that joint injury may begin before synovial inflammation is visible; specifically, articular cartilage destruction with synovitis may develop as a result. A comparatively modest number of chondrocytes are immersed in a relatively substantial volume of extracellular matrix in human articular cartilage. Collagen and proteoglycan make up the majority of the extracellular matrix. These matrix components are constantly changing, and there is a delicate balance between synthesis and breakdown. Several mediators, including growth factors, enzymes, cytokines, oxygen metabolites, and natural inhibitors, are engaged in maintaining this balance, but they are also involved in cartilage degradation when synthesis and breakdown are out of balance. The findings of these investigations reveal that exposing human cartilage to whole blood at concentrations up to 50% for a short period of time causes long-term damage. Matrix production is inhibited, and matrix breakdown, or the release of matrix components (proteoglycan release), is accelerated, resulting in a continued loss of matrix (proteoglycan content).

Hemophilia and arthritis

There are three stages of joint diseases:

  1. Acute hemarthrosis

  2. Chronic synovitis

  3. Degenerative arthritis

 

Recurrent bleeding into a joint after an episode of hemarthrosis, when the synovium lining a joint is unable to absorb enough blood, results in the presence of blood breakdown products to a level that the synovial membrane cannot eliminate. Iron, a key component of red blood cells in the blood, is thought to play a role in inflaming the synovium. The breakdown product of hemoglobin encourages the formation of pro-inflammatory chemicals such as cytokines and tumor necrosis factor (TNF), as well as enhanced synovial vascularity and hypertrophy.

 

The inflamed tissue gets trapped between the joint surfaces, and the inflammatory chemicals wreak havoc on the articular cartilage's routine maintenance. These processes combine to cause degenerative arthritis, which leads to joint deterioration.

Treatment Modality system for the Management of disorder Establishing Homeostasis

In an acute hemarthrosis, the need of early transfusion of insufficient factor to achieve hemostasis cannot be overstated. The transfusion of insufficient factor in the form of plasma or factor concentrates sufficient to raise the patient's level to 20-25 percent of normal will establish hemostasis in the case of an acute hemarthrosis. For a period of 48-72 hours, the level of deficient factor should be kept at around 10% of normal to maintain hemostasis. The amount of factor VIII in 1 ml of fresh plasma administered intravenously for each kilogram of body weight will improve the in vivo level of activity by roughly 2% in patients deficient in factor VIII. The amount of factor IX in 1 ml of plasma administered intravenously for each kilogram of body weight will boost in vivo activity by about 1.5 percent in patients with factor IX.

The type of hemophilia, the preparations available, the approximate in vivo increase in concentration to be expected from a given quantity of deficient factor, its half-life, and the patient's clinical response all influence the preparation and quantity of deficient factor administered for acute hemarthrosis.

Joint Aspiration

Joint aspiration is a technique for lowering the amount of blood in a joint after it has bled. It can aid in the relief of pain and spasms, as well as the speeding up of rehabilitation. However, there is very little data on joint aspiration in hemophilia patients, and it is generally not suggested in consensus guidelines, save in a few circumstances. In some cases, such as hip hemarthrosis and other significant and painful hemarthroses, aspiration may be considered, and it should be done as soon as possible after a bleeding episode (12 hours). Patients with acute hemarthrosis who do not respond to factor replacement therapy within 48–72 hours or in cases where pain and swelling outweigh bleeding alone may benefit from joint aspiration. The joint should be immobilized for at least 1 hour after aspiration.

Joint Immobilization

For the treatment of acute hemarthrosis, immobilization of the afflicted joint using a splint or other appliance is commonly indicated. 13~15~1 A firm plaster of Paris back-slab splint is frequently used to immobilize the afflicted joint. Excessive pressure must be avoided, and the splint must be adequately padded. Although the use of a splint for immobilization efficiently prevents future stress to the joint, it is often not necessary for the treatment of acute hemarthroses. Splinting and immobilization of the extremity, even for a short time, causes significant muscle weakening and atrophy. We restrict weight bearing without splinting for the first 24-36 hours or as long as the joint is still uncomfortable, because the additional morbidity in terms of time lost from school or work is often considerable. After that, the patient should be encouraged to resume full ambulation.

Hyaluronidase

In the treatment of acute hemarthrosis, hyaluronidase iontophoresis has been advocated in the hopes of improving blood resorption from the joint area. Because range of motion is normally regained within 24-48 hours after early transfusion of deficient factor, the use of hyaluronidase does not appear to be necessary.

Physiotherapy

Physiotherapy is an important therapeutic option for preserving joint movement and function, reducing swelling and pain, maintaining muscular strength, and avoiding injury. It's critical that the physiotherapist understands the hemophilia patient's particular physiology and bases clinical judgments on sound research. Physiotherapy is necessary for the rehabilitation process in cases of serious joint damage and surgery. Preventive physiotherapy can be used to increase mobility, flexibility, and balance by strengthening the muscles surrounding the joints.

Synovectomy

Synovectomy is advised for refractory synovitis that is not excessively hypertrophic and does not cause extensive cartilage destruction, in order to prevent both the advancement of hemophilic arthropathy and the formation of end-stage arthropathy. Because synovectomy does not eradicate the etiology of synovitis, effective outcomes are influenced by continued therapy of the underlying disease process.

 

The use of non-surgical synovectomies is the first step in treating synovitis that has failed to respond to medicinal treatment. Radio synovectomy inactivates the synovium more reliably and quickly than chemical synovectomy. Surgical synovectomy can be done open or using arthroscopy, which minimizes the need for large incisions, is associated with less frequent loss of motion, and allows for speedier rehabilitation and a more comprehensive removal of synovial tissue.

Prevention of hemophilic arthritis

The ultimate goal of management is to prevent persistent hemophilic arthropathy and its devastating repercussions. In order to delay, if not completely prevent, the development of chronic arthropathy, prompt transfusion of deficient factor at the onset of acute hemarthrosis is critical. Prophylactic deficiency factor treatment to prevent joint bleeding has also been investigated. Patients with recurrent hemarthroses in a single joint have benefited from this type of treatment. However, the cost of this treatment, the amount of deficient factor required, and the problems associated with transfusions once or three times a week make it unaffordable for most patients over the long term.

In our experience, a continual physical therapy program to preserve joint mobility and give joint protection through greater muscular strength appears to be beneficial. Isometric exercises for muscle group training can be done at home with regular monitoring of joint mobility and muscle strength. Isometric or light resistance workouts with weighted cuffs for strengthening the protective muscle groups surrounding joints with many hemarthroses appear to help reduce the number of hemarthroses. A method for preventing hemophilic arthropathy, whether it is a treatment for acute hemarthrosis, prophylactic deficient factor transfusion, synovectomy, a physical therapy program, or another medication, must be evaluated over time using objective measures like the progressive roentgenographic changes described earlier.

References

 

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