Before the development of clotting factor for hemophilia, patients with this rare disease often did not survive to adulthood.1 For this reason, hemophilia-related joint disease has not historically been a research priority.1 Now, however, those with hemophilia can expect full life spans, and part of the consequence of this improved survival is the emergence of hemophilic joint disease.1
Joint pain can occur when patients with hemophilia bleed into a joint space after an injury or for no specific reason.2 The pressure this bleeding places on the joint cavity causes substantial pain and can lead to chronic inflammation and permanent joint damage.2 Some signs of a joint bleed may include warmth in the affected joint, swelling, tingling within the joint, pain, restricted mobility or stiffness.2 Children can also be affected by joint bleeds, although they may not be able to articulate their symptoms. Signs to look for include crying, irritability, favoring one hand or leg, and refusing to walk.2
There are currently many treatments for hemophilic joint pain, and if caught early, there is no permanent damage. Patients and clinicians must be aware of the signs of a joint bleed and address the problem as soon as possible.1
The pain of bone on bone The joint damage that occurs with hemophilia is similar in mechanism to the damage seen in arthritis. 2 Like arthritic joint damage, hemophilia-related joint damage occurs in the synovium surrounding certain joints.2 The blood vessels in the synovium are the cause of bleeding into the joints in those with hemophilia.2 One role of the synovium is to eliminate fluid from the joint, and when blood is present, it is absorbed by the synovium.2 Because blood has iron, it is hypothesized that the iron in the blood thickens the lining of the synovium.2 With this thickening of the synovium comes an increase in blood vessels, thus increasing the risk of future bleeds.2 Cartilage around the bone is also affected by bleeding into the joint area. Cartilage serves the purpose of cushioning two bones connected in a joint, allowing them to move without rubbing against each other.2 The abrasion of bone rubbing against bone is painful. In the case of a hemophilia-related joint bleed, enzymes from the inflamed synovium essentially destroy this cartilage that protects the bones. As the cartilage deteriorates, the friction between the bones causes pain.2
Managing acute joint bleeds Administering clotting factor concentrate when a joint bleed is first detected is the recommended approach to managing acute bleeds.2 The patient should be evaluated, and the location of the bleed determined.2 In cases of severe bleeding that could be fatal, particularly in the head, neck, chest and gastrointestinal tract, clotting factor should be given even before diagnostic evaluation.2 Â If enough factor is available, a regimen of 6 to 8 weeks of secondary prophylaxis with intensive physiotherapy may be helpful.2 Inflammation may be reduced through a course of NSAIDs.2 Â First aid can also be administered and may include protection, rest, ice, compression and elevation, or PRICE.2 The pain from a joint bleed may require more than these measures, however.3 In terms of medications for pain, the first approach is paracetamol/acetaminophen.2 If this is not adequate to relieve pain, a COX-2 inhibitor or paracetamol/acetaminophen plus codeine three to four times daily should be used.2 The next recommended line of treatment is paracetamol/acetaminophen plus tramadol, three to four times daily. Finally, if pain persists despite these medications, a slow-release morphine product can be used, with an escape of a rapid release.2
Synovectomy In cases of persistent synovitis accompanied by frequent bleeding not otherwise controlled, synovectomy may be recommended.2 Approaches to synovectomy include chemical or radioisotopic synoviorthesis, as well as arthroscopic or open surgery.2 Nonsurgical synovectomy is currently considered the standard of care.2 A radioisotopic procedure utilizing a pure beta-emitter can be done in an outpatient setting, and it is effective and has few adverse effects.2 A period of recovery is needed for the patient to restore strength, proprioception and normal use of the joint. 2 In the absence of a radioisotope, chemical synoviorthesis is an alternate option. This approach involves weekly injections of rifampicin or oxytetracycline.2 The injections call for the use of intra-articular xilocaine for pain, as well as oral analgesics and clotting factor concentrate before each injection.2 Although the chemicals used are inexpensive, this is counteracted by the necessary frequency of factor concentrate injections.2 Surgical synovectomy is considered an option only once other approaches have been exhausted. In addition to being invasive, the procedure requires a large amount of clotting factor, and the recovery period is lengthy.2
Joint replacement In certain patients with hemophilia-associated joint damage, joint replacement may be indicated.4 This surgery is usually reserved for severe cases, in which a persistent joint bleed has led to chronic synovitis or the irreparable damage to the articular cartilage and subchondral bone.4 This condition is known as chronic hemophilic arthropathy and leads to pain, stiffness and disfigurement, causing major functional impairment.4 Because patients with hemophilia may experience severe joint disease at an earlier age than the population at large, these patients are especially advised to delay the surgery for as long as possible.4 Surgery is most frequently advised only in the case of incapacitating, bone-on-bone joint disease.4 Surgery also may be considered if a patient’s joint pain interferes with daily life.4 Joint replacement surgery is not a suitable option for all patients, however.4 Patients who have an active infection should not undergo joint replacement.4 Other possible reasons to exclude a patient with hemophilia from joint replacement surgery are local skin problems and comorbidities that would affect outcomes, such as AIDS and liver disease.4 Additionally, it may be useful to consider the compliance history with the patient’s existing hemophilia regimen, as habitual noncompliance may predict a poor outcome.4 Total joint replacement calls for the patient to be dedicated to performing rehabilitation exercises.4 Although noncompliance is not considered a contraindication, it is worth consideration by the patient, the surgeon and the hemophilia treatment center staff.4 Because bleeding and infection are risks in joint replacement surgery for these patients, a successful outcome calls for a collaborative effort consisting of orthopedic surgeons, hematologists, physical medicine and rehabilitation doctors, physiotherapists and other providers.5 According to a 2016 study by Tobase and colleagues, invasive orthopedic procedures in patients with hemophilia are waning.6 In the study, researchers evaluated patterns in orthopedic surgery in patients with hemophilia who were in the Universal Data Collection (UDC) program between 2000 and 2010.6 In collaboration with the CDC, the researchers culled annual data from 130 hemophilia treatment centers in the United States. They found that during the 11-year study interval, there was a 5.6% reduction in all invasive orthopedic treatments in all joints of patients with hemophilia enrolled in the UDC program.6
The importance of prophylaxis Ideally, successful treatments for hemophilia-related joint damage would obviate the need for treatment altogether.7 In a study conducted by the CDC and the U.S. Hemophilia Treatment Center Network, researchers evaluated 6,196 males aged 2 to 69 years with severe hemophilia A. These patients were seen at hemophilia treatment centers in the U.S. between 1999 and 2010.7 A separate study assessed 2,908 boys and young men to establish the optimal age for beginning prophylaxis to preserve joint function and mobility.7 The researchers found that between 1999 and the conclusion of the study, the use of prophylactic treatment to prevent bleeds increased from about one-third to one-half of all patients.1 Moreover, joint bleeds as well as other internal bleeding episodes decreased during the study period, and in most cases, this reduction was more significant for patients using prophylactic treatment.7 In the study of young men and boys, the researchers found that prophylaxis reduced bleeding at any age, but only patients who initiated prophylaxis before age 4 years (who were nonobese) maintained normal joint function.7 Physical exercise is also encouraged for patients with hemophilia, for purposes of overall fitness, normal neuromuscular development, muscle strengthening, healthy body weight and self-esteem.2 Because individuals with hemophilia may have reduced bone density, weight-bearing exercise that engenders bone density is encouraged.2 The choice of exercise should be based on the individual’s preference, but high contact sports such as soccer, rugby, wrestling and boxing should be avoided.2 Vulnerable joints can be shielded with braces or splints during activities.2 Overall, time is of the essence when it comes to hemophilia-related joint disease. Prophylaxis is the ideal strategy and is more possible today than ever.2 In the case of a bleed, prompt recognition and treatment can halt the progression of joint damage.2 Joint damage left untreated can be debilitating.2 Through a cooperative effort between patients, hematologists and orthopedists, many cases of hemophilia-associated joint damage can be stopped before they begin. – by Jennifer Byrne
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