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 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 5  |  Issue : 3  |  Page : 75-85

Guidelines of management of musculoskeletal complications of hemophilia


Department of Orthopedic Surgery, Collage of Medicine, Taibah University, Al-Madinah Al-Munawarrah, King Fahad Hospital, Al-Madinah Al-Munawarrah, Saudi Board of orthopedics, Saudi Commission for Health Specialties, Riyadh, Saudi Arabia

Date of Web Publication30-Sep-2014

Correspondence Address:
Mousa Mohammad Alhaosawi
Al-Madinah Al-Munawarrah, P.O Box - 3113
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-5127.141988

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  Abstract 

Hemophilia is an X-linked heritable coagulopathy with an overall prevalence of approximately 1 in 10,000 individuals. The most common form is factor VIII deficiency (hemophilia A), which comprises approximately 80% of cases. Factor IX deficiency (hemophilia B), comprises approximately 20% of cases. In patients with hemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of hemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (hemophilic synovitis) that contribute to end-stage degeneration (hemophilic arthropathy); with pain and limitation of motion severely affecting patients' quality of life. The author conducted a comprehensive review and synthesis of the relevant literature. The author reviewed all compiled reports from computerized searches. Searches were limited to English-language sources and human subjects. Literature citations were generally restricted to published manuscripts appearing in journals listed in Index Medicus and reflected literature published up to July 1, 2013. The aim of this updated paper is to provide comprehensive and timely evidence-based guidelines and recommendations on the treatments of damaged joint among hemophilia patient. Further recommendations included the control of risk factors, interventional approaches for treatment of hemophilia, the use of bypassing factors for the inhibitors, and preventing recurrent bleeding especially in high-risk populations are provided. Prophylaxis by replacement of the missing factor in patients with hemophilia is the optimal way to prevent the occurrence of haemarthrosis and thereby the onset of arthropathy, provided that it is started early in life. Dosing should be individualized and increased in case of bleeding. Prevention of bleeding episodes through early treatment will prevent accumulation of blood in joint and the subsequent inflammation and potential hemophilic arthropathy. Treatment must be maintained until bleeding remission and patients have recovered as much of their ROM and muscular strength as possible. Clinical evaluation of the joints, gait, motion, muscle tone, functional level of disability, pain, and swelling, as well as imaging techniques, must be performed to assist in the diagnosis of chronic synovitis and to guide treatment decisions. The first step to treating synovitis, refractory to medical treatment, is the use of synovectomies, non-surgical or surgical interventions. In many cases, joint deformities have to be treated by open orthopaedic surgery. State-of-the-art treatment of patients with hemophilia requires a multidisciplinary team. Level of evidence: Level III (Systematic Literature review).

Keywords: Hemophilia, joint, prevention


How to cite this article:
Alhaosawi MM. Guidelines of management of musculoskeletal complications of hemophilia. J Appl Hematol 2014;5:75-85

How to cite this URL:
Alhaosawi MM. Guidelines of management of musculoskeletal complications of hemophilia. J Appl Hematol [serial online] 2014 [cited 2019 Jul 23];5:75-85. Available from: http://www.jahjournal.org/text.asp?2014/5/3/75/141988


  Introduction Top


Hemophilia is an X-linked heritable coagulopathy with an overall prevalence of approximately 1 in 10,000 individuals. [1] The most common form is factor VIII deficiency, or hemophilia A, which comprises approximately 80% of cases. Factor IX deficiency, or hemophilia B, comprises approximately 20% of cases. [1] In patients with hemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of hemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (hemophilic synovitis) that contribute to end-stage degeneration (hemophilic arthropathy); with pain and limitation of motion severely affecting patients' quality of life. Depending on the severity of the disease, based on factor levels, the bleeding episodes are frequent and spontaneous in severe hemophilia (<1%) or occur mostly after minor trauma in moderate hemophilia (1-5%). In a patient with mild hemophilia (5-40%) bleeding usually occurs only with major trauma or surgery. Joint damage occurs progressively in patients with hemophilia, leading to functional decline and disability, which highly increases after joint bleeding and the proinflammatory cytokines interleukin 1 and tumor necrosis factor-a are thought to play a key role in promoting cartilage and bone erosion in the hemophilic arthropathy. The aim of this paper is to provide the orthopedic surgeons with the most up-to-date evidence-based recommendations for the prevention and treatment of joint damage among hemophilia patients.


  Materials and methods Top


The author conducted a comprehensive review and synthesis of the relevant literature. The author reviewed all compiled reports from computerized searches. Searches were limited to English-language sources and human subjects. Literature citations were generally restricted to published manuscripts appearing in journals listed in Index Medicus and reflected literature published up to July 1, 2013. Because of the scope and importance of certain ongoing clinical trials and other emerging information, published abstracts were cited for informational purposes when they were the only published information available, but recommendations were not based on abstracts alone. The references selected for this document are exclusively for peer-reviewed papers that are representative but not all-inclusive, with priority given to references with higher levels of evidence. All reviewers had frequent opportunities to review drafts of the document and reach a consensus with the final recommendations.


  Rating scheme for the strength of the recommendations Top


Class I: Conditions for which there is evidence and/or general agreement that the procedure or treatment is useful and effective

Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment

Class IIa: Weight of evidence or opinion is in favor of the procedure or treatment

Class IIb: Usefulness/efficacy is less well established by evidence or opinion

Class III: Conditions for which there is evidence and/or general agreement that a procedure or treatment is not useful/effective and in some cases may be harmful.


  Discussion Top


Acute Joint Hemorrhage (Hemarthrosis)

A joint bleed is defined as an episode characterized by rapid loss of range of motion as compared with baseline that is associated with any combination of the following. [1]

  • Pain
  • An unusual sensation in the joint, palpable swelling, and warmth of the skin over the joint.


In the children with severe hemophilia, the first spontaneous hemarthrosis typically occurs before 2 years of age, but may occur later. If inadequately treated, repeated bleeding will lead to progressive deterioration of the joint and muscles [Figure 1].
Figure 1: Lafeber FP et al. Haemophilia 2008; 14 (Suppl 4):3-9 (permitted from Angiola Rocino presentation)

Click here to view


This will lead to severe loss of function due to joint deformity, loss of motion, muscle atrophy and contractures within the first one to two decades of life. The origin of the bleeding is the synovium, which is a very delicate and highly vascular tissue that lines and lubricates the joint space. Very early bleeding in joints may be recognized by the person experiencing it as a tingling sensation and tightness within the joint. This "aura" precedes the actual occurrence of the clinical features of acute hemarthrosis-pain, swelling, and limitation of motion. Once blood fills the joint cavity, the joint will appear swollen and feel warm and tender. This will cause the joint to seek the most comfortable position, which is flexion. Any attempt to change this position causes more pain, thus limiting motion. Secondary muscle spasm follows as the patient tries to prevent any motion.

A re-bleed is defined as worsening of the condition either on treatment or within 72 h after stopping treatment.

The Goal of Treatment of Acute Hemarthrosis

The goal of treatment of acute hemarthrosis is to stop the bleeding as soon as possible. Ideally, this should occur when a person recognizes the "aura".

Guidelines for the management of acute hemarthrosis

· The most important initial step in the management of the acute hemarthrosis is factor replacement as soon as possible at a level sufficiently high to stop the bleeding [Table 1]
Table 1: Relationship of bleeding severity to clotting factor level (modified from guidelines for the management of the hemophilia, the world federation of hemophilia 2005)

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· The most effective method of providing immediate factor replacement is to have a home therapy program in place that allows the informed patient with hemophilia (or his/her family members) to give the factor at the appropriate time.

· Other measures to help control bleeding and provide pain relief:

  • Rest in the position of comfort
  • Immobilization (partial and temporary) with splints, pillows, slings, and crutches depending on the joint affected
  • Ice packs can be applied immediately for 20 min and can be repeated every 2 h for at least the first 12 h. Ice should not be in direct contact with the skin
  • Elevation of the affected joint
  • Tolerable pressure bandage can be used
  • Use of narcotics as analgesics should be carefully monitored, but preferably avoided because of the chronic nature of the bleeding episodes and the risks of addiction
  • Certain cyclooxygenase 2 inhibitors (COX-2 inhibitor) non-steroidal anti-inflammatory drugs (NSAIDs) may be used judiciously as pain killer e.g., meloxicam
  • Aspiration: With an acute hemarthrosis, aspiration (removal of the blood from the joint) may be considered under certain circumstances. Once there is a large accumulation of blood in the joint, the early removal of the blood should result in a rapid relief of pain and theoretically reduce the damage effects of the blood on the articular cartilage.


Joint aspiration is usually not practical, however, because ideally it should be done very early following a bleeding episode (<12 h) and must be done in a medical facility by a physician.

Situations When Joint Aspiration Considered

  • A hemarthrosis that has not responded to factor replacement within 48-72 h
  • Pain and swelling out of proportion with bleeding alone, in which circumstances a septic joint must be ruled out


Guidelines of joint aspiration in hemophilia

  • No aspiration should be done when there is overlying skin infection
  • The presence of inhibitors should also be considered as a reason for persistent bleeding in the face of adequate factor replacement and must be ruled out before aspiration is performed
  • When aspiration is performed, it should be done under factor levels of at least 30-50% for 48-72 h
  • A large bore needle, at least 16 gauge, should be used
  • The joint should be completely immobilized for 1 h after the aspiration
    • Joint aspiration should not be done in circumstances where such factor replacement is not available
    • In the presence of inhibitors, other appropriate hemostatic agents should be used for the procedure, as needed [2]
    • Joint bleeding that does not respond within 12-24 h should be evaluated by a healthcare provider.


Response to treatment of acute hemarthrosis can be defined as: [1]

  • Excellent: Complete pain relief within 8 h and/or complete resolution of signs of bleeding after initial injection and not requiring any further replacement therapy within 72 h
  • Good: Significant pain relief and/or improvement in signs of bleeding within approximately 8 h after a single injection, but requiring more than one dose of replacement therapy within 72 h for complete resolution
  • Moderate: Modest pain relief and/or improvement in signs of bleeding within approximately 8 h after initial injection and requiring more than one injection within 72 h but without complete resolution
  • None: No or minimal improvement, or worsening of the condition, within approximately 8 h after the initial injection.


Note: These definitions may require modification for inhibitor positive patients receiving bypassing agents as hemostatic cover or patients who receive factor concentrates with extended half-lives.

Guidelines of physiotherapy in acute hemarthrosis

Physiotherapy must be stressed as an active part of the management of acute joint bleeding episodes which include:

  • As soon as the pain and swelling begin to subside, the patient should attempt to change the position of the affected joint from a position of comfort to a position of function
  • Gradually decreasing the flexion on the joint and striving for complete extension
  • Gentle, passive stretching and more importantly active muscle contractions to gain extension
  • The sooner the joint is in a position of function, the active muscle exercise, and proprioceptive training must be instituted and continued until complete pre-bleed joint range of motion and functioning are restored, and signs of acute synovitis have dissipated. [3]


Muscle Hemorrhage (hematoma)

A muscle bleed is defined as an episode of bleeding into a muscle, determined clinically and/or by imaging studies, generally associated with pain and/or swelling and functional impairment. [1] The most critical sites of bleeding are those that have a risk of compromising the neurovascular function. These include:

  • The iliopsoas muscle which may cause femoral nerve palsy
  • The gastrocnemius muscle which causes posterior tibial nerve injury and muscle contracture leading to equines deformity
  • The flexor group of forearm muscles is causing a Volkmann's ischemic contracture.


Symptoms of muscle bleed includes: Aching in the muscle, Severe pain if muscle is stretched, Maintenance of the limb in a position of comfort, Tension and tenderness upon palpation.

Early identification and proper management of muscles bleeds are important to prevent permanent contracture, re-bleeding, and the formation of psuedotumours.

Guidelines of management of muscle bleed

  • These muscle bleeds require thorough clinical evaluation and monitoring
  • Factor replacement should be initiated immediately, ideally when patient recognizes the first signs of discomfort or after trauma
  • Severe bleeds in the critical sites often require repeat infusions and higher levels of factor replacement for 2-3 days or much longer duration [Table 2] [4],[5],[6],[7],[8]
  • The patient should be monitored continuously for neurovascular compromise; fasciotomy may be required in some cases after factor replacement [9],[10]
  • Hemoglobin level should be checked and corrected if needed as muscle bleeds can result in significant blood loss
  • Other measures to help control bleeding and provide pain relief
    • Rest in the position of comfort
    • Immobilization (partial and temporary) with splints, pillows, slings, and crutches depending on the limb affected
    • Ice packs can be applied immediately for 20 min and can be repeated every 2 h for at least the first 12 h. Ice should not be in direct contact with the skin
    • Tolerable pressure bandage can be used
    • Use narcotics as analgesics should be carefully monitored, but preferably avoided because of the chronic nature of the bleeding episodes and the risks of addiction
    • Certain COX-2 inhibitor NSAIDs may be used judiciously as pain killer e.g., meloxicam
  • Physiotherapy should begin as soon as pain subsides and should be progressed gradually to restore full muscles length, strength, and function. [5],[11]
Table 2: Recommended plasma factor level and duration of administration, when there is no significant resource constraints (modified from guidelines for the management of the hemophilia, the world federation of hemophilia 2005)

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Iliopsoas Hemorrhage

Iliopsoas muscle has a unique presentation. The signs of bleeding may include:

  • Pain in the lower abdomen, groin, and/or lower back pain
  • Pain on extension, but not on rotation of the hip joint
  • Paresthesia in the medial aspect of the thigh or other signs of femoral nerve compression such as loss of patellar reflex and quadriceps weakness.


The symptoms may mimic acute appendicitis, including a positive blumberg's sign.

Guidelines of management of iliopsoas bleeding

  • Immediately raise the patient's factor level, and maintain the levels for 5-7 days or longer, as symptoms indicate [Table 2] [12],[13],[14]
  • Hospitalize the patient for observation and control of pain
  • It is useful to confirm the diagnosis and monitor recovery with an imaging study (ultrasonography, computed tomography [CT] scan, or magnetic resonance imaging [MRI]) [12],[13],[14]
  • Maintain strict bed rest. Ambulation with crutches is not permitted, as ambulation requires contraction of the muscle [12],[13],[14]
  • Limit the patient's activity until pain resolves and hip extension improves
  • A carefully supervised program of physiotherapy is key to restoring full activity and function and preventing re-bleeding. Restoration of complete hip extension before returning to full activity is recommended [12],[13],[14]
  • If residual neuromuscular deficits persist, further orthotic support may be necessary.



  Chronic musculoskeletal complications of hemophilia Top


Chronic Hemorrhage (Hemarthrosis)

Once a joint develops recurrent bleeding episodes (target joint) chronic changes occur. These changes affect all of the tissues within and surrounding the joint; synovium, cartilage, capsule, ligaments, bone and muscles.

The management of chronic hemophilic hemarthrosis depends on the stage at which it is seen:

  • Chronic synovitis
  • Contracture and deforming arthropathy.


Chronic Synovitis

Chronic synovitis is usually seen in the first and second decades of life. With repeated bleeding in a joint, the synovium becomes chronically inflamed and eventually hypertrophies, causing the joint to appear grossly swollen. Muscle atrophy is often present while a relatively good range of motion of the joint is preserved.

Diagnosis made by performing a detailed physical examination of the joint. The presence of synovial hypertrophy may be confirmed by ultrasonography or MRI. Plain radiographs and particularly MRI will assist in defining the extent of articular changes.

Guidelines of chronic synovitis management

  • Factor concentrate replacement, ideally should be given with the frequency and dose levels sufficient to prevent recurrent bleeding [15],[16],[17],[18]
  • If concentrates are available in sufficient doses, short treatment course (6-8 weeks) of periodic prophylaxis with intensive physiotherapy is beneficial
  • In some cases NSAIDs (COX-2 inhibitors) may be useful to reduce inflammation [19],[20]
  • Intra-articular injection of a long-acting steroid in advance stage of synovits.
  • Physiotherapy include: [11],[21]
    • Daily exercise to improve muscle strength and maintain joint motion
    • Modalities to reduce secondary inflammation, if available [22]
    • Functional bracing, which allows the joint to move with ability to prevent new bleeding. [23]
    • Functional training [24]
  • In late stage synovectomy.


Synovectomy

Synovectomy should be considered if chronic synovitis persists with frequent recurrent bleeding not controlled by other means.

Options for synovectomy include: [25],[26]

  • Non-surgical (medical) synovectomy
  • Surgical synovectomy.


Non-surgical (medical) synovectomy

Non-surgical (medical) synovectomy should be the procedure of choice for treatment of chronic hemophilic synovitis, which can be radiosynovectomy or chemical synovectomy.

Radiosynovectomy (radioisotopic synovectomy)

  • It is commonly accepted today that radiosynovectomy is the procedure of choice
  • It can be performed at any age (ideally >12 years of age). Intra-articular injection in very young child may be difficult because it requires patient co-operation, and this may require general anesthesia
  • Should be performed under factor coverage to avoid the risk of re-bleeding during the procedure
  • Radiosynovectomy can be performed even in patients with inhibitors
  • The radioisotopes currently used for radiosynovectomy are beta-emitting (minimizing the whole body exposure to radiation that gamma radiation can produce), which are Yttrium-90 ( 90 Y), Rhenium-186 ( 186 Rh) and Phosporus-32 [27],[28]
  • The recommended isotope for the knee is 90 Y at a dose of 185 Megabecquerels (MBq). 186 Rh is better for elbows at a dose (56-74 MBq) and ankles at a dose (74 MBq) [27],[28]
  • A single dose of clotting factor is often sufficient for a single injection of the isotope.
  • On average, radiosynovectomy has a 75% satisfactory outcome in the long term. But in 25% of cases radiosynovectomy fails to control hemarthroses (radioisotope injection can be repeated).


The technique of radiosynovectomy

  • It is performed in out-patient clinic
  • No local anesthetic is required
  • Strict asepsis must be maintained throughout the procedure.
  • Size 12-14 gauge needle (in order to evacuate a viscous hemarthrosis)
  • Once the needle reached should be used the intra-articular space all liquid content should be evacuated (Blood or synovial fluid)
  • The contents of the radioisotope loaded syringe should be injected slowly into the joint
  • Withdraw the needle very slowly whilst at the same time injecting an anti-inflammatory drug (e.g. betamethasone) in order to avoid the risk of the radioactive burn of the needle track or an adjacent skin
  • After removal of the needle, a compression bandage should be applied for 3 days.


Chemical Synovectomy

If a radioisotope is not available then, chemical synovectomy is an appropriate alternative. [29] Either rifampicin or oxytetracycline chlorhydrate can be used. [30] Chemical synovectomy requires weekly injections until the synovitis is controlled, (usually 6 injections). These painful njections require the administrations of intra-articular xilocaine a few min before injection of a sclerosing agent, oral analgesics (a combination of acetaminophen/paracetamol and an opioid) medication. Chemical synovectomy should be performed under factor concentrate coverage to avoid the risk of re-bleeding during the procedure.

Surgical Synovectomy

Surgical synovectomy is seldom necessary today and is only considered when other less invasive and equally effective procedures fail. Surgical synovectomy, whether open or arthroscopic, requires enormous resources from an experienced team, a dedicated hemophilia treatment center, and a large supply of clotting factor for both surgery and lengthy period of rehabilitation.

  • Preoperative factor levels should be 80-100%
  • Postoperative factor level should maintain above 50% in the 1 st week and above 30% in the late postoperative period
  • Continuous infusion appears safe and effective
  • The use of antifibrinolytic agents and thromboprophylaxis could be considered in certain settings.


Contracture and Deforming Arthropathy

This can develop any time from the second decade of life, sometimes earlier, depending on the severity of bleeding and its treatment. It is caused by a persistent chronic synovitis and recurrent hemarthroses resulting in irreversible damage to the joint cartilage. With advancing cartilage loss, progressive arthritis develops along with secondary soft tissue contractures, muscle atrophy and angular deformities, [Gilbert classification [Table 3]]. With advancing chronicity of the arthropathy, there is less swelling due to progressive fibrosis of the synovium and the capsule, and loss of motion with flexion contractures causing the most significant functional loss.
Table 3: Clinical features of hemophilic arthropathy (Gilbert classification) (modified from guidelines for the management of the hemophilia, world federation of hemophilia 2005)

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The radiographic features of chronic hemophilic arthropathy depend on the stage of involvement.

  1. Arnold-Hilgartner classification [Table 4]
  2. Peterson classification [Table 5]
Table 4: Arnold-Hilgartner classification (modified from guidelines for the management of the hemophilia, the world federation of hemophilia 2005)

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Table 5: Peterson classification (modified from guidelines for the management of the hemophilia, the world federation of hemophilia 2005)

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  • Early changes will show soft tissue swelling, epiphyseal overgrowth and the osteoporosis
  • Cartilage space narrowing will vary from minimal to complete loss
  • Bony erosions and subchondral bone cysts will develop, causing irregular articular bony surfaces which can lead to angular deformities
  • Fibrous/bony ankylosis may be present


Stage II: Osteoporosis and overgrowth of the epiphysis, no cyst, no narrowing of the cartilage Space [Figure 2]
Figure 2: Stage III

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Stage III: Early subcondral bone cyst, squaring of the patella, widened notch of the distal femur or humerus, preservation of the cartilage space.[Figure 3]
Figure 3: Stage II

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Stage IV: Finding of stage III, but more advanced; narrowed cartilage space [Figure 4]
Figure 4: Stage IV

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Stage V: Fibrous joint contracture, loss of the joint cartilage space, extensive enlargement of the epiphysis, substantial disorganization of the joint.[Figure 5]
Figure 5: Stage V

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goal of chronic hemophilic arthropathy treatment is to improve joint function and relive pain. Treatment options will depend on:

  • The stage of the condition
  • The patient's symptoms
  • The resources are available.


Guidelines of management of chronic hemophilic arthropathy

Conservative management

  • Serial casting to assist in correcting deformities [31],[32]
  • Bracing and orthotics to support painful and unstable joints [23]
  • Walking aids or mobility aids to decrease stress on weight-bearing joints
  • Adaptations to the home, school, or work environment to allow participation in community activities and employment and to facilitate activities of daily living. [33]


Surgical management

If the conservative measures fail to provide satisfactory relief of pain and improved function, surgical intervention may be considered.

Procedures depending on the specific condition needing correction which may include:

  • Extra-articular soft tissue release to treat contractures
  • Arthroscopy to release intra-articular adhesions and correct impingement [34]
  • Elbow synovectomy with radial head excision [35]
  • Osteotomy to correct an angular deformity.
  • Prosthetic joint replacement for severe disease involving a major joint (knee, hip, shoulder, elbow) [36]
  • Arthrodesis of the ankle which provides excellent pain relief and correction of deformity with marked improvement in function. [37],[38]


Physiotherapy management

The role of a physiotherapist includes

1. Assessment

  • Determining the need and demand of the patient for physiotherapy
  • Regular assessment throughout the life
  • Pre-operative assessment.


2. Education

  • Of the patient and family regarding musculoskeletal complications and their treatment
  • Of school personnel regarding suitable activities for the child, immediate care in case of a bleed, and modifications in activities that may be needed after bleeds.


3. Treatment

  • Factor replacement is necessary if recurrent bleeding occurs during physiotherapy
  • Pain control with appropriate analgesics
  • Narcotics should be avoided when possible
  • Non-steroidal anti-inflammatory drugs (certain COX-2 inhibitors) may be used to relieve arthritic pain
  • Hydrotherapy, heat, ice, electrical nerve stimulation, pulsed diathermy, ultrasound as well as various orthoses for pain relief and restoration of function.


Pseudotumors

A potentially limb and life-threatening condition unique to hemophilia is the pseudotumor. It is most commonly seen in a long bones or pelvis. It occurs as a result of inadequately treating a soft tissue bleed, usually in muscle adjacent to bone, which can be secondarily involved. If not treated, the pseudotumor can reach enormous size causing pressure on the neurovascular structures and pathologic fractures. A fistula can develop through the overlying skin.

Clinical features include:

  • Diagnosis is made by the physical finding of a localized mass
  • Radiographic findings include a soft tissue mass with adjacent bone destruction [Figure 6]
  • A more detailed and accurate evaluation of a pseudotumor can be obtained with CT scan or MRI [Figure 7] and [Figure 8].
Figures 6: Plan X-ray showed pseudotumors of the distal index finger

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Figures 7: CT Scan showed pseudotumors of anterior thigh muscles

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Figures 8: MRI showed pseudotumors of gluteus medius muscles

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Guidelines for the management of pseudotumors

Management depends on the site, size, rate of growth and effect on adjoining structures.

  • A 6-week course of treatment with factor is recommended, flowed by repeat MRI. If the pseudotumor is decreasing, continue with factor and repeat MRI for three cycles [39],[40]
  • Proceed to surgery if necessary, which will be much easier if pseudotumor has shrunk
  • Aspiration of the pseudotumor followed by injections of fibrin glue, arterial embolization, or radiotherapy may heal some lesions. Surgery may be needed for others [41],[42]
  • Surgical excisions, including limb amputations, may be necessary for large pseudotumors, particularly if they erode long bones. Large abdominal pseudotumors present a special challenge in surgical management of hemophilia; surgery must only be performed by teams with experience in hemophilia.


Fractures

Fractures are not uncommon in the patients with hemophilia, possibly due to lower levels of ambulation and intensity of activities, [43] and occur most commonly around the knee and hip. The patients with hemophilia are at risk for fracturing around joints that have significant loss of motion and in bones that are osteoporotic.

Guidelines of treatment of a fracture in hemophilia

  • Immediate factor concentrate the replacement. [43],[44],[45]
  • Factor levels should be raised to at least 50% and maintained for 3-5 days [43],[44],[45],[46]
  • Lower levels may be maintained for 10-14 days while the fracture becomes stabilized and to prevent soft tissue bleeding
  • The actual management of the fracture should be performed in a manner appropriate for the specific fracture, and this includes operative treatment if needed under appropriate coverage of clotting factor concentrates
  • Care should be taken to avoid prolonged immobilization that could lead to a significant limitation of range of motion in the adjacent joints [43],[44]
  • Circumferential plaster should be avoided; splints are preferred [43]
  • Physiotherapy should be started as soon as the fracture is stabilized to restore range of motion, muscle strength and function.


Pain management in patients with musculoskeletal complications of hemophilia

Acute and chronic pains are common in patients with hemophilia. Adequate assessment of the cause of pain is essential to guide proper management.

Guidelines of pain management in patients with hemophilia

  • If for any reason medications have been stopped for a period of time, patients who have been taking and tolerating high-dose narcotic drugs should re-start the drug at a lower dose, or use a less powerful painkiller, under the supervision of a physician [Table 6]
  • Cyclo-oxygenase two inhibitors should be used with caution in patients with hypertension and renal dysfunction.
Table 6: Modified from guidelines for the management of the hemophilia, the world federation of hemophilia 2005

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Monitoring Outcome of Treatment

Patients should be evaluated once every 6-12 months for:

  • Musculoskeletal status: Measure clinical scores annually and radiological scores as indicated
  • Use clotting factor concentrates
  • Inhibitor development: Perform screening tests for inhibitors
  • Transfusion-related infections (if appropriate): Evaluate for HIV, HCV and HBV infections commonly and other infections if indicated
  • Quality of life.



  Conclusions Top


Prophylaxis by replacement of the missing factor in patients with hemophilia is the optimal way to prevent the occurrence of hemarthrosis and thereby the onset of arthropathy, provided that it is started early in life. Dosing should be individualized and increased in case of bleeding. Prevention of bleeding episodes through early treatment will prevent the accumulation of blood in joint and the subsequent inflammation and potential hemophilic arthropathy. Treatment must be maintained until bleeding remission and patients have recovered as much of their ROM and muscular strength as possible. Clinical evaluation of the joints, gait, motion, muscle tone, functional level of disability, pain, and swelling, as well as imaging techniques, must be performed to assist in the diagnosis of chronic synovitis and to guide treatment decisions. The first step to treating synovitis, refractory to medical treatment, is the use of synovectomies, non-surgical or surgical interventions. In many cases, joint deformities have to be treated by open orthopedic surgery. State-of-the-art treatment of patients with hemophilia requires a multidisciplinary team.


  Acknowledgments Top


The author wish to acknowledge Luigi Piero Solimeno (Italy); Abdullah Sandokji (Taibah University); Khalid khoshal (Taibah university); Zakaria ohammed Hamza Alhawsawi; and Ahmad M Tarawah (Maternity and children Hospital) for their assistance in reviewing and preparing this guidelines and recommendations.

 
  References Top

1.White GC 2 nd , Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J, et al. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the Scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 2001;85:560.  Back to cited text no. 1
    
2.Hermans C, De Moerloose P, Fischer K, Holstein K, Klamroth R, Lambert T, et al. Management of acute haemarthrosis in haemophilia A without inhibitors: Literature review, European survey and recommendations. Haemophilia 2011;17:383-92.  Back to cited text no. 2
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]


This article has been cited by
1 Musculoskeletal treatment in haemophilia
Bülent Atilla,Hande Güney-Deniz
EFORT Open Reviews. 2019; 4(6): 230
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