Chapter Outline
Hemophilia
Sickle Cell Disease
Hemophilia
Hemophilia, a genetically determined disorder, is characterized by abnormal blood coagulation as a result of a functional deficiency of factor VIII or IX. Since biblical times, the crippling deformities of the musculoskeletal system and death resulting from uncontrolled hemorrhage have been well depicted in the pages of history.
The term hemophilia, coined by Hopff in 1828, means “blood loving.” Wright is credited with being the first to demonstrate the prolonged clotting time in the disorder. Patek and Taylor isolated the deficient substance, terming it antihemophilic globulin.
Modern management of hemophilia has reduced the morbidity of the disease remarkably. The development of human immunodeficiency virus (HIV) infection in those receiving blood products has been a major setback. Better treatment of HIV infection and safer methods of blood product screening and factor preparation have reduced the effect of this unfortunate disease complex. Currently, factors VIII and IX are produced with recombinant DNA methods, which avoids the hazards of bloodborne disease. During the HIV era, the mortality rate of patients with hemophilia was determined to be two to three times higher than that of the general male population, largely because of the consequences of viral infections. Interestingly, studies have continued to show that the mortality rate of patients with hemophilia who were not infected with HIV continue to exceed the mortality rate of the general population by a factor of 2.6.
Incidence
The incidence of hemophilia is estimated to be 1/10,000 male births in the United States and 0.8/10,000 male births in England. A 1998 study estimated the national prevalence at 13,320 cases of hemophilia A and 3640 cases of hemophilia B, with a U.S. birth prevalence of both A and B of 1/5032 live male births.
Classification and Inheritance
Hemophilia may be classified as hemophilia A, hemophilia B, or von Willebrand disease. Hemophilia A and B are further classified as mild, moderate or severe, based on the functional plasma factor levels ( Table 43-1 ). Patients with severe hemophilia may have spontaneous hemarthroses, intramuscular bleeding, and visceral bleeding, even in the absence of trauma.
| Severity | Factor Level (Percentage of Normal) |
|---|---|
| Mild | >50 |
| Moderate | 25-50 |
| Moderately severe | 1-24 |
| Severe | <1 |
Hemophilia A
Hemophilia A, or classic hemophilia, results from a congenital deficiency in factor VIII (also known as antihemophilic factor or antihemophilic globulin). This type accounts for about 80% of cases and is caused by a gene carried on the X chromosome. Studies have identified at least 58 different mutations that result in a deficiency in normally functioning factor VIII protein.
Hemophilia A occurs in boys and is transmitted by asymptomatic female carriers. A girl could be affected if her mother were a carrier and her father a hemophiliac; however, this is very rare.
Hemophilia B
Hemophilia B, or Christmas disease, is caused by a deficiency in factor IX (plasma thromboplastin component, or Christmas factor). Its clinical manifestations are similar to those of classic hemophilia. The hereditary transmission also is by an X-linked recessive gene. As with hemophilia A, many mutations of the gene responsible for factor IX production have been identified. Hemophilia B accounts for approximately 15% of cases of hemophilia.
von Willebrand Disease
In this bleeding disorder, factor VIII deficiency and platelet functional abnormality are present. The disorder is inherited as an autosomal dominant trait and occurs in both genders. The bleeding disorder is relatively mild.
Factor VIII, a glycoprotein with a molecular weight of 2000 kDa, is composed of subunits, each with a molecular weight of approximately 200 kDa. All these subunits contain carbohydrates and are held together by disulfide bonds. The precoagulant, sex-linked, hemophilic defect is located on the lighter protein portion of the glycoprotein, whereas the autosomal dominant von Willebrand defect is related to the heavier carbohydrate moiety of the molecule.
Clinical Features
Hemorrhage
Uncontrolled hemorrhage and repeated episodes of bleeding are the hallmarks of hemophilia. The severity of the disease varies from patient to patient but is constant in any one patient. Clinical manifestations of hemophilia A and B are similar and depend on the blood levels of factor VIII or IX. The level of hemostasis is normal when the blood level of either factor is at least 50% of normal. When the functional plasma level of the factor is 25% to 50% of normal, the hemophilia is mild, and excessive bleeding occurs only after major trauma or during surgery. When the plasma level of the factor is 5% to 25% of normal, the hemophilia is moderate; severe, uncontrolled bleeding occurs after minor injury or during an operative procedure. When the plasma level of the factor is 1% to 5% of normal, the hemophilia is moderately severe, with major hemorrhage occurring after minor injury or unrecognized mild trauma. When the plasma levels of factor VIII or IX are below 1% of normal, the hemophilia is considered very severe; clinically there are repeated spontaneous hemorrhages into joints and bleeding into deep soft tissues.
Abnormal bleeding may occur in any area of the body. Joints are the most frequent sites of repeated hemorrhage, followed by muscles and soft tissues. In the patient with severe hemophilia, the abnormal bleeding tendency may manifest in the neonatal period or early infancy. Ordinarily the ecchymosis and soft tissue bleeding are minor, resorb relatively readily, and are not detected by the parents. When the infant begins to crawl and starts bumping into objects, or is standing and falling, abnormal bleeding into joints and soft tissues is noted by the parents. At this stage the infant is usually seen by the pediatrician. It is crucial to have a high index of suspicion for hemophilia to prevent serious consequences or invasive treatment, such as aspiration of the joints.
Hemophilic Arthropathy
Intraarticular hemorrhage is a central clinical hallmark of hemophilia. A single hemarthrosis may precipitate low-grade synovitis, which predisposes the involved joint to recurrent hemarthrosis and a cycle of chronic synovitis, inflammatory arthritis, and progressive arthropathy.
Site of Involvement.
The weight-bearing joints are the most common sites of hemophilic arthropathy, with the frequency of involvement being, in decreasing order, the knee, elbow, shoulder, ankle, wrist, and hip. The vertebral column is rarely involved. Any joint, however, may be the site of pathologic change.
Pathophysiology.
The pathophysiologic process was initially described by Konig in the late nineteenth century. An initial stage of synovial reaction to the bleeding into the joint occurs first, followed by a later stage of cartilage degeneration and joint destruction. After injury, the synovial vessels rupture and the blood accumulates in the joint. Bleeding continues until the intraarticular hydrostatic pressure exceeds arterial and capillary pressure in the synovium, resulting in tamponade of the synovial vessels and causing ischemia of the synovium and subchondral bone.
With repeated hemorrhage, hyperplasia and fibrosis of the synovium occur, and a vicious circle of bleeding-synovitis-bleeding ensues. Pannus formation by the proliferating synovial tissue erodes the hyaline cartilage peripherally, and compression of its opposing cartilaginous surfaces results in degeneration of articular cartilage centrally. Articular cartilage is also degraded by the action of proteolytic enzymes—lysosomal proteases, acid phosphatase, and cathepsin D. Data from animal studies have suggested that articular cartilage may be more susceptible to blood-induced damage at younger rather than at older ages. Prostaglandin levels are also elevated in hemophilic arthropathy. An inflammatory process invades and destroys cartilage. Loss of joint motion and contractures from the capsular synovial fibrosis follow. Local ischemia causes formation of subchondral bone cysts.
Repeated hemarthrosis causes marked dilation of the capsular and epiphyseal vessels. The resultant hyperemia and increased circulation to the part result in enlargement of the epiphysis and increased length of the limb. Stimulation of growth may be asymmetric, resulting in valgus or varus deformity. Alternatively, shortening of the limb may be produced by early closure of the physis. Osteoporosis and muscle atrophy are common.
Clinical Findings.
Clinical findings depend on the severity of hemorrhage and whether the hemarthrosis is acute, subacute, or chronic. In acute hemarthrosis, pain and swelling with distention of the joint capsule are the principal findings. A history of injury may not be elicited. With cessation of bleeding, the intensity of the pain decreases. The joint will assume the position of minimal discomfort, which is also the position of minimal intraarticular pressure. The hip joint, for example, is held in flexion, abduction, and external rotation. Extension, wide abduction, and medial rotation of the hip are limited and painful because they increase intraarticular hydrostatic pressure. The knee joint is held in flexion, with range of motion markedly restricted by protective spasm, pain, and the hemarthrosis. Local tenderness and increased heat are present. The overlying skin becomes tense and shiny. The intense pain of acute hemarthrosis subsides rapidly after the administration of factor VIII or IX.
Subacute hemarthrosis develops after several episodes of bleeding into the joint. Pain is minimal. The synovium is thickened and boggy. Joint motion is moderately restricted. Subacute hemarthrosis does not respond rapidly to the administration of clotting factor.
Chronic hemarthrosis develops after 6 months of involvement. Progressive destruction of the joint takes place, with the end stage being a fibrotic, stiff, and totally destroyed joint.
Differential Diagnosis.
A difficult diagnostic challenge is the child with hemophilia and a superimposed joint infection. The diagnosis is often delayed because the symptoms are similar to those of hemarthrosis. In one series, most but not all children with infection were found to have elevated white blood cell counts. Associated risk factors included infected angioaccess catheters, pneumonia, and generalized sepsis. Affected joints should be treated with antibiotics and repeated aspiration or arthrotomy.
Radiographic Findings.
Radiographic findings associated with hemarthrosis depend on the stage of the disease, patient age at disease onset, and the joint involved. Magnetic resonance imaging (MRI) is considered the most accurate imaging modality for assessing hemophilic arthropathy and may significantly affect patient management. Initial radiographs of an affected joint disclose soft tissue swelling from distention of the joint capsule. With repeated hemorrhage and resultant chronic synovitis there may be joint effusion, osseous erosion, osteoporosis, enlargement of the epiphysis, subchondral cysts, narrowing of the articular cartilage space, formation of peripheral osteophytes, and other secondary degenerative changes ( Figs. 43-1 and 43-2 ). The final phase of hemophilic arthropathy is fibrous ankylosis ( Fig. 43-3 ).
On the basis of radiographic findings and degree of cartilage destruction, Arnold and Hilgartner classified hemophilic arthropathy into five stages ( Box 43-1 ). A modified version of the Arnold-Hilgartner system has four grades instead of five ( Box 43-2 ). This modified classification eliminates the original stage II (epiphyseal enlargement and juxtaarticular osteoporosis), which is rarely discrete and has no implications for treatment. Osteoporosis frequently accompanies chronic synovitis in patients with stage I arthropathy, and erosions are often present, with epiphyseal enlargement.
Stage I
Soft tissue swelling
No skeletal abnormality
Stage II
Overgrowth and osteoporosis of epiphysis
Joint integrity maintained
No bone cysts
No narrowing of articular cartilage space
Stage III
Mild to moderate joint narrowing
Subchondral cysts
Patellar squaring
Widening of intercondylar notch of knee and trochlear notch of elbow
Articular cartilage preserved, indicating that disease is still reversible
Stage IV
Severe narrowing of joint space, with cartilage destruction
Other osseous changes, subchondral cysts, patellar squaring, widening of intercondylar or trochlear notch, very pronounced
Stage V
Total loss of joint space with fibrous ankylosis
Marked incongruity of the articular structures, with severe irregular hypertrophy of the epiphysis
Grade I
Soft tissue fullness indicating effusion and synovial thickening
Juxtaarticular osteopenia often present
Grade II
Widened epiphysis, surface irregularity, and small erosions
Normal cartilage interval or joint space
Grade III
Narrowing of cartilage interval with extensive surface erosions
Juxtaarticular bony cysts may be present
Grade IV
Same findings as stage III, but with complete loss of cartilage interval and marked surface irregularity
Reactive sclerosis, squaring of the margin of the femoral condyles, and subluxation often present
In a study comparing the ability to detect synovial hypertrophy using plain radiography and MRI, Arnold-Hilgartner staging alone was proven to be predictive of synovial hypertrophy in patients with symptomatic knee and ankle joints, with a sensitivity and specificity of 100% for the detection of synovial hypertrophy within the knee.
Soft Tissue Bleeding
After a direct injury, a large hematoma may accumulate in the subcutaneous tissues. The blood usually is absorbed spontaneously; ulceration occasionally occurs, commonly on the forehead, the olecranon process, or the prepatellar area. This type of superficial hematoma usually remains fluid and fluctuant for a long time. Superficial soft tissue hemorrhage in the form of ecchymosis is common, especially in a patient with severe hemophilia; it is not of clinical significance.
Intramuscular and Intermuscular Hemorrhage
In the lower limb the most common site of bleeding is the quadriceps (44%), followed by the triceps surae (35%), anterior compartment (7%), adductors of the thigh (7%), hamstrings (6%), and sartorius (1%). In the upper limb the most common site of bleeding is the deltoid (24%), followed by the wrist and finger flexors in the forearm (23.5%), brachioradialis (19.5%), biceps (14%), wrist and finger extensors in the forearm (11%), and triceps (8%). The presenting complaint is pain on movement or at rest.
Hemorrhage in the quadriceps muscle may occasionally be painless and manifest only as stiffness or weakness of the knee. Physical findings consist of local tenderness and swelling, with limitation of motion of the adjacent joints. Bleeding in the deltoid muscle restricts shoulder motion, especially abduction and, to some extent, rotation, flexion, and extension of the shoulder. Bleeding in the forearm flexors restricts motion of the fingers, wrist, or elbow, individually or in combination.
Hemorrhage into the iliopsoas muscle or retroperitoneum may mimic a variety of surgical or medical emergencies, such as appendicitis or renal colic.
Ischemia and fibrosis of muscles, with subsequent myostatic contracture, result from bleeding within muscles or among muscles contained in a firm fascial compartment. Hemorrhage within the calf muscles produces fixed equinus deformity. Bleeding in the volar surface of the forearm may produce a Volkmann ischemic contracture, with flexion deformity of the digits and wrists ( Fig. 43-4 ).
Diagnostic Ultrasonography
Diagnostic ultrasonography is routinely performed in hemophilic patients in whom hemorrhage into joints or soft tissues is suspected. It is noninvasive and can be performed at the bedside, with minimal disturbance of the patient. *
* References .
The diagnostic value of ultrasonography is in the identification of bleeding into the hip, shoulder, and deep soft tissues, such as the iliopsoas or retroperitoneum ( Fig. 43-5 ). Effusions into these deep anatomic sites are easily detected on ultrasonography. Hemorrhage into superficial joints such as the knee, elbow, ankle, or wrist is determined on physical examination.
The echo pattern varies with the duration and anatomic site of the hemorrhage. In the soft tissues a hematoma initially displays increased echogenicity compared with surrounding soft tissues; within 3 to 4 days, relatively echo-free areas develop in the bleeding site. Ordinarily, in 10 days, the established hematoma is relatively echo-free. A soft tissue hematoma may be of uniform texture, separating muscle planes, or it may interdigitate with muscle fibers, producing a mottled appearance, with poorly defined margins. On follow-up ultrasonographic examination, the intramuscular hematoma may have resolved spontaneously or may have progressively liquefied, with decreased internal echoes and the development of well-defined borders. A sudden increase in echogenicity indicates a fresh hemorrhage.
The echo pattern of bleeding into joints shows a mixture of echo-free fluid within the joint and a variable amount of echogenic material floating free. In its initial stage hemarthrosis is sometimes uniformly echogenic, in contrast to the echo-free appearance of joint effusions from other causes, such as toxic synovitis or septic arthritis.
Measurements of synovial thickness and synovial vascularity using ultrasonography in conjunction with power Doppler sonography have been shown to correlate highly with the determination of these parameters using MRI. The use of Doppler sonography with ultrasound may therefore be a less costly means for determining the extent of synovial involvement; this may prove useful in patients under consideration for selective prophylaxis prior to sustaining a frank hemarthrosis.
Nerve Palsy
Neurapraxia in hemophilia is primarily caused by compression of a nerve from the hematoma. The femoral nerve is usually involved because it is in a closed rigid compartment limited by the iliacus fascia. The psoas sheath is easily distensible. The nerve next most frequently affected is the median nerve. The ulnar, radial, sciatic, peroneal, and lateral femoral cutaneous nerves also may be involved.
A history of injury, such as twisting of the limb or strenuous use, may be obtained in some cases. Pain is the presenting complaint and is soon followed by weakness of the affected muscle groups.
In femoral nerve palsy, the hip is held in moderate flexion and some lateral rotation. Extension and medial rotation of the hip are limited and painful. On palpation a tender mass in the iliac fossa extending to the iliac crest and groin may be present. There will be anesthesia or hypesthesia in the areas of the cutaneous distribution of the femoral nerve. Quadriceps paralysis is often present, in varying degrees. Ultrasonography and computed tomography (CT) demonstrate the iliacus hematoma. With adequate factor replacement, the natural course is one of gradual and steady recovery, usually within 12 months. †
† References .
Hemophilic Pseudotumor
The term hemophilic pseudotumor refers to a progressive cystic swelling involving the musculoskeletal system. It is caused by uncontrolled hemorrhage within a confined space. The hematoma grows and causes pressure necrosis and erosion of surrounding tissues. The subjacent bone frequently is involved.
First described in 1918, this entity occurs only in severely affected hemophiliacs who have a functional clotting factor level below 1% of normal. In these patients, with severe hemophilia, the estimated incidence is 1% to 2%.
These cysts develop in one of three ways. The simple cyst occurs within the fascial envelope of a muscle (or muscles) and is confined by the tendinous attachments. No bony changes are seen on radiographs. The cyst usually remains localized under the muscle fascia, although it may extend between muscle and fascia to point internally or through the skin.
The second type of cyst occurs in a muscle with wide and firm fibrous periosteal attachments; it may eventually cause cortical thinning because of compressive interference with the periosteal and outer cortical blood supplies.
In the third type, the pseudotumor originates as a subperiosteal hemorrhage and progressively strips the periosteum from the cortex until it is limited by the aponeurotic or tendinous attachments. The overlying muscle is raised or destroyed. Most hemophilic pseudotumors are caused by subperiosteal hemorrhage. Occasionally one may arise from intraosseous hemorrhage. In the past, intramedullary bleeding was thought to be a cause of hemophilic pseudotumor. It was proposed that uncontrolled intraosseous hemorrhage increases the intramarrow pressure and causes necrosis of the marrow and inner cortex of the bone. With progressive bleeding and increasing pressure, the cortex would perforate, causing elevation of the periosteum and bone necrosis. Pathologic examination of large hemophilic pseudotumors, however, has failed to demonstrate bone necrosis or resorption of the inner part of the cortex.
The most common location of pseudotumors is in the thigh (50% of cases), followed by the abdomen, pelvis, and tibia ( Fig. 43-6, A ). Pseudotumor may also occur in the hand (see Fig. 42-6, B ). Pseudotumor involving the calcaneus may cause marked erosion of the calcaneal tuberosity.
A bone involved by pseudotumor may sustain pathologic fracture. Before adequate factor replacement was available, pseudotumors caused death in most patients, and involved limbs were amputated. Fernandez de Valderrama and colleagues have observed that the location of these tumors is related to the powerful muscle groups of the quadriceps femoris, triceps surae, gluteus maximus, and iliopsoas muscles, which have firm attachments between their fibers and the periosteum but not to any great extent with the bone itself. These muscles also have profuse vascular connections with the underlying periosteum and bone. Hemorrhage from these injured vessels easily detaches and elevates the periosteum.
Hemophilic pseudotumor is essentially an expanding hematoma. CT scans have demonstrated that the lesion is of fluid consistency and can show its true extent, bony destruction, and extraosseous abnormality. MRI is also of great value in delineating the nature and extent of the pseudotumor. It is imperative that a hemophilic tumor not be mistaken for a malignant or expanding benign bone tumor. It should not be aspirated, nor should a biopsy specimen be taken for diagnosis, particularly without appropriate preoperative correction of functional factor deficiency.
Fractures
Fractures in hemophilia may result from trauma or may occur pathologically after a trivial injury. They are most common in the lower limb, especially in patients with stiff knees, who sustain supracondylar fracture of the femur. Fracture hematomas may be large, especially after femoral fractures. Uncontrolled bleeding into a closed fascial compartment may lead to a Volkmann ischemic contracture (see Fig. 43-5 ).
Dislocations
Intraarticular bleeding in the hip stretches the joint capsule and causes subluxation and eventual dislocation of the hip. Bleeding in the hip joint is a rare but serious problem in hemophilia. Increased intraarticular pressure, in addition to stretching the joint capsule, causes avascular necrosis (AVN) of the femoral head, with eventual joint space narrowing, subchondral irregularity and cyst formation, collapse of the femoral head, osteoarthrosis, and arthrokatadysis.
Myositis Ossificans
Ectopic ossification in hemophilia, first described by Hutcheson, develops as a result of intermuscular or intramuscular bleeding. Heterotopic bone formation around the hip joint restricts motion of the hip. In the past it was thought to be a rare complication in hemophilia, but has been reported to occur in 15% of patients.
Bone Mineral Density
Children with severe hemophilia and hemophilic arthropathy are at risk for reduced bone mineral density related to limitations in weight-bearing exercise and frequent hepatitis C infection. Although more recent research has suggested that only a small number children with moderate or severe hemophilia may have abnormal bone mineral density, reduced bone density in childhood remains a risk factor for osteoporosis in later life. Because osteoporosis may therefore complicate the future treatment of patients with hemophilia, screening for reduced bone density of young patients with severe hemophilia is recommended until further studies have explored this issue.
Treatment
The care of the hemophiliac with musculoskeletal disorders requires a multidisciplinary approach by a team consisting of a hematologist, orthopaedic surgeon, physical therapist, nurse clinician, medical psychologist, social worker, and geneticist. There should be immediate access to a laboratory capable of performing accurate factor VIII and IX assays and detecting factor antibodies. Factor material should be readily available for replacement therapy. The creation of multidisciplinary hemophilia clinics in children’s hospitals has simplified the care of hemophilic children.
Gene Therapy
A number of trials of gene therapy in animals with genetically produced factor deficiencies have been performed, with some success. Most studies have addressed the use of adenoviral vectors to carry the corrected gene into the recipient, with the goal of obtaining long-term therapeutic levels of factor VIII or IX without stimulating an immune response against the transgene product or the vector itself. Host immunity to the adenoviral vector has thus far prevented permanent correction of the factor deficiency, although the development of viral vectors devoid of viral genes has allowed reduced immunogenicity and even sustained expression of factors VIII and IX, with complete cure of the bleeding disorder in some investigational settings.
Specific gene therapy methodologies that have been investigated include the modification of hematopoietic stem cells to express factor VIII transgene in the megakaryocytic lineage, allowing platelets to store and deliver factor VIII to the site of vascular injury. Permanent therapeutic correction of mutations in the factor IX gene has been reported in a mouse model of hemophilia B, without the development of host immune reactions. Despite these intriguing developments, gene therapy remains an investigational method, with many obstacles to be overcome before it can be reliably used as a treatment for hemophilia.
Medical Management
The objective of medical management is control of bleeding by hemostasis, achieved by intravenous (IV) administration of the appropriate coagulation factors. There are two major approaches. The first is treatment on demand—that is, at the onset of any bleeding episode. The second approach is prophylactic replacement in patients with recurrent hemarthroses.
Treatment on Demand
The most common approach to the treatment of recurrent hemarthrosis is treatment on demand. It has been suggested that factor levels of 30 to 50 IU/dL are optimal in controlling an acute hemorrhage. To achieve these levels in a patient with severe hemophilia (plasma levels < 1% of normal), 15 to 25 IU/kg of factor VIII and 20 to 50 IU/kg/dL of factor IX are required. Repeated treatments may be required daily for 2 to 3 days to control the hemarthrosis. Aspirin products and nonsteroidal antiinflammatory drugs must be avoided. An investigation into the cost implications of repeated arthrosis in patients with hemophilia A has found that the cost of treating a child with on-demand factor VIII more than doubled within 1 year after the development of a target joint, defined as three bleeds into a single joint within a 3-month period. This study, performed in boys with an average age of 4.5 years, supports beginning primary prophylactic therapy at younger ages.
Prophylactic Treatment
Several studies have shown that ongoing prophylactic treatment reduces the incidence of hemarthrosis. One study has found that starting treatment at 3 years of age results in a better outcome than starting at 5 years, but patients with prior repeated hemarthrosis had continued arthropathy despite prophylactic factor replacement. Another study noted reduced bleeding frequency in 41 of 47 patients but an increase in the cost of clotting factors compared with treatment on demand, although a similar investigation identified fewer joint bleeds, less arthropathy, and lower treatment costs in 49 patients receiving factor prophylactically versus on demand.
The efficacy of prophylactic treatment for the prevention of hemarthrosis and arthropathy in children has been highlighted by two prospective, multicenter, randomized trials. The recent ESPRIT study in Europe has demonstrated that when compared with patients randomized to demand treatment, those receiving prophylactic factor replacement have significantly fewer hemarthroses and less signs of arthropathy on plain radiography. Patients who initiated prophylaxis prior to 36 months of age had fewer joint bleeds per month and no radiographic signs of arthropathy. The Joint Outcomes Study in the United States randomized 65 boys younger than 30 months with hemophilia A to receive prophylactic or demand recombinant factor VIII replacement therapy. The mean annual number of joint bleeds was significantly higher in the demand treatment group. Furthermore, at 6 years of age, 93% of boys in the prophylaxis group had normal MRI studies of the knees, ankles and elbows versus only 55% in the demand group.
The dosage required to replace a factor deficiency depends on the patient’s weight and plasma volume. The hematologist makes the calculation and is in charge of administering the factor. The orthopaedic surgeon, however, should be aware that 20 to 30 minutes after administration of the antihemophilic factor, the plasma level will rise. The biologic half-life of factor VIII is 6 to 12 hours, whereas that of factor IX is 8 to 18 hours. In the management of bleeding into joint, muscles, and soft tissue, the dose of factor VIII or IX is calculated to raise the plasma level to 30% of normal. In severe hemarthrosis it may be desirable to raise the plasma level to 40% of normal.
Inhibitors of factors VIII and IX develop as a result of the human immunologic response. Risk factors for inhibitor development include a family history of inhibitory antibodies, high risk–factor VIII gene mutations, and intensive initial factor treatment. Also, black patients are twice as likely to develop inhibitors to factor VIII as white patients. A low titer of inhibitors may be circumvented by high-dosage factor VIII infusion. Other methods to overcome this life-threatening problem include the administration of prednisone and cyclophosphamide, the use of high concentrations of prothrombin-activated material, and the use of plasmapheresis. Immune tolerance therapy can eradicate inhibitors but has not been uniformly successful. Preliminary data have suggested that prophylaxis with activated prothrombin complex concentrates safely reduces the incidence of joint bleeding during immune tolerance therapy and in patients in whom immune tolerance induction fails. Controlled clinical trials are needed, however, to identify whether prophylaxis can prevent joint bleeding and damage and improve the quality of life in patients with factor inhibitors.
Early Treatment of Bleeding into Muscles and Soft Tissues
Early treatment of bleeding into muscles and soft tissues by the self-administration of factor VIII or IX by the hemophiliac or parent at home has been found to be effective. The dose of factor is calculated to raise the level to 30% to 40% of normal. The part is splinted in a comfortable neutral position in foam pillows or soft appliances. If the hemorrhage is in the lower limb, weight bearing is restricted by crutches or eliminated by confinement to the bed or a wheelchair. As soon as the acute symptoms of pain and muscle spasm have subsided, the affected limb is gradually mobilized while factor replacement is continued. With early treatment (within 2 to 3 hours), the hemorrhage in the muscles usually resolves within 3 to 5 days. Hemorrhages in the quadriceps femoris and biceps brachii take the longest time to resolve.
Acute Treatment of Hemarthrosis
Acute bleeding into joints is an emergency requiring immediate attention. With proper education and instructions about dosage schedules, many patients can be treated at home by themselves or by a family member. Immediate treatment of bleeding into joints results in less arthropathy and minimizes the extent of joint destruction. Home therapy permits factor replacement as soon as a bleeding episode takes place. This type of patient self-help, however, has the disadvantages of inadequate follow-up, the possibility of transmission of hepatitis to a family member, and an increased risk of infection because of lack of appropriate sterile technique in the handling of materials. The parents should be instructed that if the bleeding is severe, with marked distention of the joint, the child should be brought to the hospital within 4 hours of the onset of hemorrhage. It cannot be overemphasized that delay in instituting adequate treatment is the primary cause of crippling joint deformity in patients with hemophilia. A minimal or moderate intraarticular hemorrhage may not be so painful at the onset, and the child will continue to use and bear weight on the affected limb, causing continuous or intermittent progressive bleeding into the joint. Within a few days, the joint becomes markedly swollen, very painful, and inflamed by reaction to the blood, and it develops a fixed flexion contracture. In case of associated bleeding into the periarticular tissues and muscles, pain and muscle spasm are marked from the onset; the patient is apprehensive of moving the limb and is forced to rest and seek medical attention.
The affected joint is temporarily immobilized in a molded, well-padded splint in a position of rest and minimum hydrostatic pressure. This position varies with each joint. For example, for the knee, it is 35 to 45 degrees of flexion, and for the elbow it is 50 to 60 degrees of flexion. Commercially available semiflexible splints (e.g., Jordan splint) provide partial immobilization and moderate compression.
Compression is effectively achieved by placing a rubber sponge and elastic bandage over the site of hemorrhage. A second bandage may be applied intermittently over the first one to increase tension. The distal circulation should be carefully watched. Under no circumstances should a circular plaster cast be used, because the swelling underneath will obstruct blood flow and cause gangrene or compartment syndrome. The limb should be elevated to reduce hydrostatic venous pressure. Cold compresses in the form of ice bags are applied to the affected joint. The clotting defect is corrected by IV administration of antihemophilic factor.
Analgesics
Narcotic analgesics are used with care because in such a chronic disease, addiction can easily become a problem. Also, the course of the bleeding is best assessed by the patient, and after being given a heavy analgesic, he or she will be unable to give proper warning of continued bleeding.
A diminution in the severity of the pain is the first indication of cessation of hemorrhage. The circumference of the joint is measured at intervals to determine whether there is progressive distention of the joint capsule. Also, analgesic drugs that contain aspirin, guaiacolate, and antihistamines inhibit platelet aggregation and prolong the bleeding time. Administering these medications could produce a secondary bleeding disorder. If the pain is intolerable and does not respond to factor replacement and splinting, the pain medications to be given are propoxyphene (Darvon), acetaminophen (Tylenol), codeine, or methadone. A double-blind, controlled placebo study has found that etoricoxib, a cyclooxygenase-2 (COX-2) inhibitor, provides significant improvement in various outcome measures assessing pain and function versus placebo, with no increased incidence of hemarthrosis in patients with hemophilic arthropathy.
Aspiration
The need for joint aspiration has been debated. Some authors recommend aspiration only for an extremely tense hemarthrosis and avoid aspiration in ordinary cases, citing the risk of introducing infection, discomfort to the patient, and possibility that aspiration will incite more bleeding. Others believe that the removal of blood is critical for avoiding chronic synovitis and that a large hemarthrosis is much more inviting to infecting organisms than sterile aspiration of the joint.
Joint aspiration should be performed under strict aseptic conditions and under local anesthesia. Factors VIII and IX are administered IV and reach an effective blood level 20 to 30 minutes later, at which time the joint should be aspirated. Later aspiration, after two to three infusions have been given, will be unsuccessful because of the thickening and clotting of the hemarthrosis. Aspiration is performed with an 18-gauge lumbar puncture needle with a stylet. One or at most two puncture wounds should be made with the needle. The joint is irrigated with normal saline solution until the return is clear. The compression dressing and posterior splint are reapplied.
The appropriate factor is administered for 3 to 7 days after cessation of bleeding. At this time physical therapy to mobilize the joint is initiated. Isometric muscle exercises are begun, followed by gentle assisted range-of-motion (ROM) exercises, first with gravity eliminated and then against gravity. Between exercises the limb is protected in an appropriate splint. The ROM of the affected joint is progressively increased. Weight-bearing joints are protected with crutches with a three-point gait. Full weight bearing is not permitted for a minimum of 2 weeks, longer if necessitated by limitation of joint motion and muscle weakness. Transition to activity must be gradual.
Subacute Hemophilic Arthropathy
Repeated episodes of bleeding into a joint in a relatively short time result in synovial hypertrophy and persistent effusion. This is best managed nonoperatively by immobilization of the joint in a well-padded splint and with factor replacement. Most subacute hemarthroses resolve over a period of 3 to 4 weeks with this regimen. Aspiration is not indicated. Isometric exercises are performed to maintain muscle tone and strength. Initially, passive ROM exercises are not allowed. Partial weight bearing with crutches is permitted. With resolution of the synovitis and effusion, the patient is allowed to return to normal function gradually.
If the subacute hemarthrosis fails to respond to 3 weeks of partial immobilization, physical therapy, and factor replacement, an intraarticular injection of corticosteroid may be given. Prolonged immobilization of the affected joint should be avoided because it will result in marked muscle atrophy and restriction of joint motion. If the knee is involved, quadriceps atrophy will cause joint instability, leading to repeated trauma and bleeding.
Support of the lower limb in orthotic devices is indicated in two cases—when the motor power of the quadriceps or triceps surae muscle is less than fair or when flexion deformity of the knee or equinus deformity of the ankle is present to such a degree that mechanical insufficiency of the lower limb predisposes the child to fall and sustain repeated injury. Rubbing and recurrent trauma to the opposite thigh or leg caused by the medial caliper is a problem because it will cause soft tissue bleeding. Only a lateral upright is used. A well-padded plastic orthosis should be used whenever possible. When flexion deformity of the knee or equinus deformity of the ankle develops, appropriate splinting is used at night to keep the part out of the position of deformity. Ankle splinting may be done initially with ordinary posterior splints. Recurrent hemarthroses may be prevented by an ankle support worn during activities. Air splints, free ankle polypropylene orthoses, and lacers have all been used. Shock-absorbent heel pads also have been shown to reduce the impact on the ankle, with fewer hemarthroses resulting.
During the stage of subacute hemarthrosis, prophylactic factor replacement is administered in conjunction with an intensive physical therapy program. Graduated progressive active resisted and gentle passive ROM exercises are performed immediately after infusion of the factor in the evening and the following morning. The patient is allowed to swim and perform ordinary physical activities of daily living. Contact sports should be avoided.
Chronic Hemophilic Arthropathy
Chronic hemophilic arthropathy can usually be prevented by effective and immediate treatment of acute hemarthrosis. The importance of prevention of chronic arthropathy, with its accompanying intraarticular fibrosis, cartilage destruction, and joint stiffness, cannot be overemphasized.
In the management of chronic hemophilic arthropathy, four modalities of treatment are available—physical therapy, orthoses, traction and other corrective appliances, and surgery. The objective is to correct joint deformity and restore function.
Nonsurgical Treatment of Joint Deformity
Nonoperative measures should always be used before surgery. For flexion deformities of the knee and hip, a period of continuous traction is effective for relieving muscle spasm and increasing ROM. Traction forces are initially in the line of deformity and are gradually altered to achieve correction. Traction with a Russell splint is effective. The vertical force is exerted by a sling placed under the proximal tibia when the knee is involved; with the hip, the sling support is under the distal thigh. In cases of lateral rotation contracture of the hip, a medial rotation strap is added to the thigh.
Prophylactic protection with antihemophilic factor is usually not required for a child in traction. Once a neutral or almost neutral position is obtained, well-padded plastic splints are used to maintain the part in the corrected position. Active exercises are begun to increase muscle power and joint ROM. It is best to refrain from forceful passive stretching exercises.
If functional ROM is not achieved after 2 or 3 weeks of traction, a wedging cast is applied. Posterior subluxation of the knee may be prevented by applying an extension-desubluxation hinge; this will lift the proximal tibia anteriorly as the knee is extended. For safety, antihemophilic factor is administered when the cast is wedged. When full knee extension is achieved, the knee is immobilized for 7 to 10 days, a plastic splint is used to maintain the correction, and physical therapy in the form of active exercises is begun. Partial weight bearing and three-point crutch gait are permitted gradually. If bleeding occurs during this period of training, it is controlled by IV administration of antihemophilic factor. Crutch support is discontinued and full weight bearing is allowed when there is functional range of joint motion and at least fair strength of the quadriceps muscle.
Management of flexion contracture of the elbow follows the same principles as those for the knee. Equinus deformity of the ankle is treated by a dorsiflexion wedging cast. Forceful manipulation of a joint under general anesthesia is not recommended.
The role of physical therapy should not be underestimated. Therapy can play an important role in preventing and managing joint contractures. Early and aggressive supervised physical therapy programs for young patients with hemophilia have demonstrated significant improvements in joint ROM and pain scores, with similar significant decreases in scores assessing disability.
Surgical Treatment of Deformity
With early treatment and proper collaboration between the hematologist and orthopaedic surgeon, deformities and crippling in patients with hemophilia can be prevented or corrected. If deformities caused by hemarthrosis cannot be corrected by conservative closed methods, one should not hesitate to perform open operations. Despite increased anesthetic risk, it is sometimes preferable to perform two or three orthopaedic surgical procedures in a single operative session to avoid repetition of surgical procedures and reduce factor consumption.
Hematologic Management
Before surgery is performed, the hematologist determines the factor level and performs tests to rule out the presence of factor inhibitors. During surgery and on the first postoperative day, the factor level should be raised to 100% by the infusion of factor concentrate, confirmed by a factor assay before surgery. The patient is then started on a continuous infusion of clotting factor to maintain levels at 60% of normal throughout the operative procedure, with this factor level maintained until hospital discharge. During the first postoperative week, the factor level is maintained at 50% and for the next 2 to 4 weeks factor levels are maintained at 30% to 40% of normal by daily home infusion of factor concentrate.
During the preoperative evaluation, children with hemophilia are screened carefully for the presence of clotting factor inhibitors. In general, patients with active inhibitors are not candidates for elective surgery but may be considered for this after the induction of immune tolerance through frequent regular infusions of clotting factor concentrate. Some patients with active inhibitors respond to the use of factor VIIa as a bypassing agent, although its efficacy in patients undergoing major surgery is controversial. In addition, the half-life of factor VIIa is approximately 2 hours, and the cost of its administration is several times that of recombinant factor VIII.
Hemophilic Arthropathy
The most common procedures used to manage hemophilic arthropathy are synovectomy, joint débridement, fusion, and arthroplasty. Despite the medical and surgical complexities of hemophilic arthropathy, these procedures typically result in symptomatic improvement and high levels of patient satisfaction. If equinus deformity is very severe and rigid, Achilles tendon lengthening is indicated. Fractional lengthening of the hamstrings combined with posterior capsulotomy is performed for flexion contracture of the knee. On occasion, one may need to resort to osteotomy of the distal femur, tilting it anteriorly to correct flexion deformity of the knee. Even in cases of marked radiographic joint destruction, corrective osteotomy can yield acceptable long-term results and may delay or avoid the need for joint replacement. Osteotomy should be contemplated primarily for patients in whom damage is unicompartmental and accompanied by corresponding axial deviation.
Acute hemarthrosis of the immature hip requires special considerations, including factor replacement and aspiration on an urgent basis to reduce the risk for development of osteonecrosis. Discerning hip hemarthrosis from iliopsoas muscle bleeds can be difficult because the symptoms of these two conditions may be identical. Iliopsoas bleeds may, however, be associated with femoral nerve palsy and numbness in the saphenous nerve distribution, whereas patients with hip hemarthrosis may demonstrate an increased femur-to-teardrop distance on anteroposterior radiographs. CT and MRI reliably differentiate between the two conditions, and high-resolution ultrasonography may also be useful.
Open surgery has become relatively safe, provided that the clotting mechanism is restored to near normal by the administration of antihemophilic factor, which should be continued for 3 weeks, with sutures removed on the 14th to 16th postoperative day. Wounds and bone heal normally in hemophilic patients.
Synovectomy.
The objective of synovectomy is to prevent the progression of hemophilic arthropathy. The rationale for synovectomy in hemophilic arthropathy is based on the following considerations. Mechanically, the vulnerability to trauma of the highly vascular synovial tissue is diminished by its excision, and biochemically, hemophilic synovial tissue has a high level of fibrinolytic activity that tends to prolong the bleeding episodes. Also, the hypertrophic synovial tissue in hemophilia contains increased levels of acid phosphatase and cathepsin D, which are further elevated during bleeding episodes; these proteolytic enzymes destroy hyaline articular cartilage. The chronic synovial inflammation is perpetuated by the elevated levels of prostaglandin E and polymorphonuclear leukocytes because of chemotactic properties of the enzymes. Also, hemosiderin deposition in the synovium interferes with the production of collagenase, which may cause death of chondrocytes.
Synovectomy of peripheral joints, particularly of the knee, is indicated for patients with a history of severe recurrent hemarthrosis (two or three major bleeding episodes per month) and for those whose condition does not respond to aggressive medical management maintained for at least 6 months. Medical management involves a prophylactic factor replacement program that raises factor levels to 30% to 40% of normal; factor replacement is administered every other day in hemophilia A and every third day in hemophilia B. Other indications are failure to respond to orthopaedic nonsurgical treatment (physical therapy and protection with crutches and orthoses) and radiographic stage II or III hemophilic arthropathy (in stages IV and V, synovectomy is ineffective and contraindicated). In the elbow, repeated hemarthroses result in the loss of forearm rotation and elbow extension. Limitation of rotation results mainly from hypertrophy of the radial head. A reduction in the incidence of hemarthrosis has been reported after open synovectomy of the elbow, with excision of the radial head to improve ROM. Synoviorthesis with radioactive gold has also been reported to be effective for reducing hemarthroses.
Arthroscopic Synovectomy.
Although open synovectomy has been used longer than the other methods, it is often complicated by the loss of ROM of the affected joint. Arthroscopic synovectomy, which has now mostly replaced open procedures, is most useful when performed before severe degenerative changes have developed. Several reports have noted a significant reduction in hemarthroses without loss of motion after arthroscopic synovectomy. A cost-benefit analysis of arthroscopic synovectomy has identified significant reductions in disease-related costs per month and in the number of hemarthroses reported before and after the procedure—$7500 versus $900, and 71 versus 7 hemarthroses, respectively. Arthroscopic procedures are difficult and often lengthy but avoid some of the motion problems of open approaches. In one study of arthroscopic synovectomy performed in 69 joints in 44 children, subjects experienced 84% fewer hemarthroses compared with control subjects. ROM remained stable or improved within 1 year in patients who underwent arthroscopic synovectomy, and complications related to the procedure were rare, although radiographic scores of patients treated arthroscopically worsened slightly during the study.
Open Synovectomy.
Open synovectomy of the knee is performed under tourniquet ischemia. The surgical approach to the knee is through a long, medial, parapatellar incision that begins 5 cm above the superior border of the patella and extends to the medial border of the patella and then to the medial border of the proximal tibial tubercle. Throughout the operation, electrocautery is used to maintain strict hemostasis. The subcutaneous tissue, fascia, and capsule are divided and the knee joint is thoroughly inspected. The proliferative synovial tissue is excised first from the suprapatellar pouch, then from the medial and lateral recesses of the knee and intercondylar notch, including that around the cruciate ligaments, and finally from the menisci. The coronary ligaments must be preserved. The synovial tissue on the articular cartilage is removed gently with a moist sponge. Growth of the distal femoral physis must not be disturbed. Next, the joint is copiously irrigated with antibiotic solution, and Gelfoam mixed with a solution of injectable saline and thrombin is applied over the denuded tissues. The wound is packed with moist laparotomy pads, and after several layers of elastic bandages have been applied for compression, the tourniquet is released. Five to 10 minutes later, the wound is inspected and thorough hemostasis is obtained. The previously applied Gelfoam is removed and the wound is closed in layers. Suction drainage is always inserted. A bulky compression dressing is applied, and the limb is immobilized in an above-knee, plaster of Paris posterior splint. The suction drainage is removed in 2 or 3 days.
Postoperative Care.
Isometric quadriceps- and hamstring-strengthening exercises are begun immediately. Active ROM exercises should not be commenced early because they could result in massive hemarthrosis. Seven to 10 days after surgery, gentle active assisted and passive ROM exercises are started. Toe-touch weight bearing with crutch protection is allowed as tolerated. Active ROM exercises are started approximately 2 weeks after surgery. Passive range of knee motion exercises may also be performed with a continuous passive motion (CPM) machine 14 days after surgery, at first for several hours of the day during waking hours to ensure that there is no bleeding into the joint, and then for gradually increasing periods. During the third postoperative week, the limb should be in the CPM machine all night and part of the day. Active exercises are performed intensively to develop quadriceps function. Full weight bearing is allowed gradually.
Problems and Complications.
Postoperative loss of range of joint motion from adhesions of the patellofemoral and tibiofemoral joints is a common and challenging problem after synovectomy for hemophilic arthropathy and may be greater in younger patients because of poor cooperation with the postoperative physical therapy program. The stage of arthropathy, adequacy of control of intraarticular bleeding during and after surgery, degree of quadriceps and hamstring atrophy, and patient’s motivation and cooperation are important factors in determining the final ROM. Intensive, prolonged physical therapy and use of the CPM machine are vital after synovectomy.
Massive bleeding may occur in the joint during the immediate postoperative period after synovectomy or during the rehabilitation phase of treatment. This may require aspiration or surgical arthroscopic evacuation of the hematoma.
Despite these complications, the results reported in the literature have indicated that chronic recurrent hemarthrosis and the pain in chronic hemophilic arthropathy can be effectively eliminated after open synovectomy, which also appears to slow the pace of progression of the disease. ‡
‡ References .
Synoviorthesis.
A number of methods of synovial ablation using intraarticular radioactive substances have been reported. Children have been infrequently treated in this manner because of unresolved concerns of future oncogenesis. Rifampicin injected intraarticularly has been shown to reduce synovial proliferation and the incidence of hemarthrosis. It seems most effective in younger patients and in smaller joints.
Radiosynovectomy is minimally invasive, does not require hospitalization, necessitates only minimal clotting factor coverage, preserves ROM better than surgical synovectomy, and is highly cost-effective compared with open surgical or arthroscopic synovectomy. This procedure can be accomplished successfully without the simultaneous co-injection of corticosteroids. Yttrium has been widely used for radiation synoviorthesis. Its use has been shown to result in a significant decrease in the frequency of bleeding episodes, but reports have differed about an association with significant rates of reduced ROM in treated joints.
Colloidal P-chromic phosphate has also been used to treat hemarthroses. In one series, all patients had a reduced incidence of hemarthrosis. Of these patients, 50% retained ROM and the other 50% gradually lost motion. Radiographic scores worsened, despite a reduction in the rate of hemarthrosis. A reduction in the incidence of hemarthrosis of the elbow has been reported with synoviorthesis with radioactive gold and with rhenium-186. Chemical and radioisotope synovectomies have been tried for the treatment of chronic hemophilic arthropathy. The results have been dubious; at present, surgical synovectomy is the procedure of choice.
Total Joint Replacement and Arthrodesis.
Deciding between total joint replacement and arthrodesis is difficult, and the decision should be individualized. Disabling pain is the prime indication for surgery.
Total Joint Replacement.
In case of bilateral knee involvement, total joint replacement is indicated with stage IV or V arthropathy when persistent knee pain is definitely caused by joint derangement; there should be at least 45 degrees of knee motion. Over the years, reported results have been good. §
§ References .
The most recent literature reports have suggested that with the use of modern, continuous factor replacement during the perioperative period, clinical outcomes can be equivalent to those of knee arthroplasty in the nonhemophilic population.Total hip replacement is indicated for stage IV or V hemophilic arthropathy when persistent pain with severe disability is not relieved by conservative measures. Total joint replacement has been shown to have no adverse effects on the course of HIV infection in patients with hemophilia. Arthroplasty of the elbow has been reported. Although the available literature on the use of total elbow replacement for hemophilic arthropathy contains small cohorts, most patients in these studies have had more pain relief, preserved function, and the ability to perform activities of daily living with minimal difficulty.
Arthrodesis.
Arthrodesis of the ankle, subtalar, and midtarsal joints in the foot and shoulder or knee may be indicated when these joints are destroyed. The surgical technique is the same as for normal patients, except that percutaneous pins should not be used in hemophilic patients because they will need factor replacement at moderate levels until the pins are removed. Arthrodesis of the hip is considered when the patient has a destroyed hip, with little involvement of the other joints. The indication is stronger when the child is unlikely to be compliant with activity restrictions and likely to overstress a total hip replacement.
Neurapraxia
Neurapraxia is treated by factor replacement therapy in a sufficient dose to attain factor levels of 80% to 100% of normal for 48 hours after onset of hemorrhage; the dose is tapered to maintain a level of 40% for 1 to 2 weeks. The limb is splinted. Gentle physical therapy is performed 7 days after the bleeding episode. Decompression of the entrapped nerve may occasionally need to be performed.
Fractures
Fractures usually heal in the normal time. Factor replacement should be to the level of 40% to 60% of normal on the day of fracture and the following day; subsequently, it should be 20% to 30% for 7 or more days, depending on the degree of associated soft tissue injury. Whenever possible, fractures are treated by closed reduction and immobilization in a cast. Pins should not be used for skeletal traction because the patient will need prolonged factor replacement therapy. External fixators should be avoided. Open reduction and internal fixation are carried out when closed methods are not appropriate.
Flexion Contractures
In areas of the world in which home infusion of clotting factor is not available, recurrent hemarthrosis is the major source of morbidity, giving rise to joint destruction and flexion contracture. Large-joint contractures have been treated successfully by Ilizarov external fixation under such circumstances, with factor IX levels maintained at 1.0 IU/mL before and after surgery. In one reported case, fixed flexion in the knee joint was reduced from 50 to 5 degrees, and the child walked freely and without pain 4 months after surgery.
Pseudotumors
Treatment of pseuodotumors remains controversial. Conservative management consists of factor replacement and close observation. Greene has recommended that pseudotumors be excised whenever they are accessible and stated that they will continue to expand if left alone. Before surgical intervention, angiography, CT, and MRI should be performed to provide accurate anatomic detail of adjacent vessels. The pseudotumor itself is avascular. The surgical extirpation of a hemophilic pseudotumor requires careful preoperative planning and extensive dissection. Surgical excision, although potentially curative, can be associated with severe intraoperative hemorrhage. The use of arterial embolization prior to surgical excision has been proposed as a means to limit operative blood loss.
Radiation therapy has been used to control the expanding hematoma of hemophilic pseudotumors; irradiation causes new bone formation and sclerosis of the cystic cavity. Its use may be considered for surgically inaccessible sites. It is important to shield the physis to avoid causing a growth disturbance. Amputation of a limb may be indicated when the patient is seen late or the patient has a deformity so severe that the limb is of no use.
Athletic Participation
Guidelines for athletic participation in children with hemophilia have begun to emerge. Several studies have documented the benefit of regular exercise in this patient population, including fewer bleeding episodes, improved muscle strength and joint stability, and increased bone mineral density with weight-bearing exercise. Furthermore, aerobic activity can temporarily improve coagulation factors in patients with mild and moderate hemophilia. A retrospective study of hemophilia patients receiving prophylaxis found no difference in the frequency of joint bleeds or injuries between those participating in high-impact and low-impact sports, and most children developed less than one bleed or injury per season. Current recommendations for athletic participation dictate that children with hemophilia receive appropriate factor prophylaxis, develop written strategies to prevent bleeds, undergo close assessment of muscle and joint function in conjunction with a physician prior to sport selection, especially for contact sports, and wear protective equipment, with knowledgeable coaching staff present to see they receive prompt treatment if they develop an acute bleed.
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