Hemophilic arthropathy is term given to changes in joints caused by recurrent bleeding into joint due to a bleeding disorder called hemophilia. Hemophilia is a genetic disorder characterized by abnormality of the coagulation mechanism due to functional deficiency of a specific blood factor, namely VIII or IX.
The name hemophilia was coined by Hopff in 1828. Wright demonstrated that the disorder involves prolonged clotting time.
The estimated incidence is between 0.8-1 per 10,000 male births. Hemophilia may be classified as follows:
This results from a congenital deficiency of factor VIII or antihemophilic factor or antihemophilic globulin. It constitutes 80 percent of cases and is X linked. Hemophilia A manifests in the male and is transmitted by asymptomatic female carriers.
Hemophilia B occurs due to a deficiency of factor IX ( also called plasma thromboplastin component or Christmas factor). It occurs in 15% of the cases and manifestations are similar to Hemophilia A. The hereditary transmission is also by an X-linked recessive gene.
Von Willebrand’s Disease
In this bleeding disorder, both factor VIII deficiency and platelet functional abnormality are present. It is inherited as an autosomal dominant trait, occurring in both males and females. The bleeding disorder is relatively mild.
Symptoms and Signs of Hemophilia
Repeated episodes of bleeding which are not easily controllable are the hallmarks of hemophilia. The severity of the disease varies from patient to patient and depends on levels of the deficient factor.
The factor is 25 to 50 of normal and excessive bleeding occurs only after major trauma or during surgery.
When the plasma level of the factor is 5 to 25 percent of normal, the hemophilia is moderate. Severe uncontrolled bleeding occurs after a minor injury or during an operative procedure.
When plasma level of the factor it is 1 to 5 percent of normal, the hemophilia is moderately severe. Severe bleeding occurs after a minor injury or unrecognized mild trauma.
When the plasma levels of factor <1%, hemophilia is considered very severe. There are repeated spontaneous bleedings into joints and bleeding into deep soft tissues occur.
In severe cases, the abnormal bleeding may manifest itself in the neonatal period or early infancy which is noticed by the parents when the child begins to crawl or walks.
Joints are the most frequent sites of repeated bleeding followed by muscles and soft tissues.
Pathophysiology of Hemophilic Arthropathy
The weight-bearing joints are most commonly affected.
Frequency of involvement knee>elbow>shoulder> ankle>wrist>hip.
The vertebral column is rarely involved.
Following injury, the synovial vessels rupture, and blood accumulates in the joint. Bleeding continues until the intraarticular hydrostatic pressure exceeds that of the arterial and capillary pressure in the synovium. This causes ischemia of the synovium and subchondral bone.
With repeated hemorrhage, hyperplasia and fibrosis of the synovium ensue.
Pannus [thickened synovial tissue] formation erodes the hyaline cartilage peripherally which leads to loss of joint motion and contractural deformity occurs.
Subchondral bone cysts are formed due to local ischemia.
An attempt to repair may lead to asymmetrical growth, resulting in valgus or varus deformity.
Early closure of physis may lead to limb shortening.
Osteoporosis and muscle atrophy are common.
The final phase of hemophilic arthropathy is fibrous ankylosis.
Clinical Presentation of Hemophilic Arthropathy
These depend on the severity of hemorrhage and whether the bleeding in the joint is acute, subacute, or chronic.
An acute bleeding in the joint will lead to pain and swelling of the joint resulting in distention of the joint capsule. This causes pain which decreases only when the bleeding stops.
On examination, the joint involved would assume a position where it is in minimum discomfort which would also be the position of minimum pressure.
For example, the hip is kept in 30 to 65 degrees of flexion, 15 degrees of abduction, and 15 degrees of lateral rotation. The knee joint is held in flexion.
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. Restriction of joint motion is moderate.
Chronic hemarthrosis develops after six months of involvement. Progressive destruction of the joint leads to a fibrotic, stiff, totally destroyed joint.
Radiograms will disclose soft-tissue swelling due to distention of the joint capsule. With repeated hemorrhage and resultant chronic synovitis, there may be
- Enlargement of the epiphysis
- Subchondral cysts,
- Narrowing of the articular cartilage space
- Formation of peripheral osteophytes.
Finding in Knee
- widened intercondylar notch
- squared inferior margin of the patella
- bulbous femoral condyles
- flattened condylar surfaces
Finding in Elbow
- enlarged radial head
- widened trochlear notch
Talar tilt due to relative undergrowth of the lateral side of the tibial epiphysis leading to a pronated foot.
Classification of Hemophilic arthropathy
The classification is based on radiographs.
Soft-tissue swelling, but no skeletal abnormalities.
Overgrowth and osteoporosis of the epiphysis, joint integrity is maintained. There are no bone cysts and no narrowing of the articular cartilage space.
The radiologic Stage II parallels the clinical stage of subacute hemophilic arthropathy.
Minimal to moderate joint space narrowing with subchondral cysts. Widening of the intercondylar notch of the knee and the trochlear notch of the ulna. In the knee, there may be squaring of the patella.
Articular cartilage is still preserved and hemophilic arthropathy is still reversible.
Destruction of articular cartilage with severe narrowing of the joint space. The other osseous changes found in stage III are more pronounced.
Total loss of joint space with fibrous ankylosis of the joint. There is marked incongruity of the articular structures with severe irregular hypertrophy of the epiphysis.
Treatment of Hemophilic Arthropathy
Treatment of Acute Episodes of Bleeding
The main concern in hemophilic arthropathy is the spontaneous bleeding. The aim of treatment is to prevent the bleeding.
This is done by replacement of deficient factor with a concentrate of the clotting factors obtained from fresh frozen plasma.
- For Factor VIII deficiency (hemophilia A and von Willebrand’s disease) the concentrate used contains factor VIII and fibrinogen. Commercially prepared cryoprecipitates are available.
- For factor IX deficiency (hemophilia B) the concentrate used contains a high level of factor IX and low levels of factors, II, VII, and X. It is manufactured as the prothrombin complex from human plasma.
In case of the management of bleeding into joints, muscles, and soft tissue, the dose of factor VIII or IX is calculated to raise the plasma level to 30 percent of normal.
In severe hemarthrosis, it may be desirable to raise the plasma level to 40 percent of normal.
One of the problems with factor replacement therapy is developing inhibitors of factor VIII and IX as a result of the immunologic response.
Initially, a low titer of inhibitors may be circumvented by high dosage of factor infusion. In severe cases, the administration of prednisone and cyclophosphamide or of plasmapheresis may be required.
It takes about 20 minutes for the plasma levels of the factors to rise.
The biologic half-life of factor VIII is 6 to 12 hours, whereas that of factor IX is 8 to 18 hours.
radioisotopes can be injected therapeutically into a joint to decrease bleeding and synovitis
The affected joint is temporarily immobilized in a position of rest and minimum intraarticular pressure.
A compression helps to create tamponade and reduce further bleeding but distal circulation should be carefully watched.
Under no circumstances should a circular plaster cast be used. The swelling will obstruct the distal circulation and cause gangrene.
The limb should be elevated and Cold compresses are applied over the affected joint. The clotting defect is corrected by administration of antihemophilic factor.
It is best to avoid analgesics or sedative. NSAIDs are contraindicated due to an inhibitory effect on platelets. With opioid drugs as addiction can be a problem with repetitive use. If the patient is under the effect of analgesia he will be unable to get a proper warning of continued bleeding.
The decrease of the severity of pain is the first indication of cessation of hemorrhage. Monitoring the circumference of the joint at intervals also tells the progress.
However, in case of need opioid drugs may be given but they should be used conservatively. If the pain is intolerable and does not respond to factor replacement and splinting, pain medications that can be given are propoxyphene, acetaminophen, codeine.
The joint should be aspirated and decompressed if there is severe hemarthrosis with marked distention of the joint capsule.
Aspiration of the joint should be performed under strict aseptic conditions in the operating room and under local anesthesia. Following that Factor VIII or IX is administered intravenously. After the aspiration, the compression dressing and posterior splint are reapplied. Administration of the factor is continued for three to seven days following cessation of bleeding.
After cessation of bleeding, physical therapy to mobilize the joint is initiated. Isometric muscle exercises, gentle active assisted exercises are carried out intermittently. The range of motion of the affected joint is progressively increased. Full weight-bearing is not permitted as necessitated by a limitation of joint motion and muscle weakness. Transition to activity is gradual.
Treatment of Hemophilic Arthropathy
The treatment depends on whether the arthropathy is acute or chronic.
Subacute hemophilic arthropathy occurs when repeated episodes of bleeding into a joint occur in a relatively short time. This results in synovial hypertrophy and persistent effusion. Subacute hemophilic arthropathy is best managed by immobilization of the joint, factor replacement and followed by physical therapy.
Most of subacute hemarthroses resolve over a period of three to four weeks.
If the subacute hemarthrosis fails to respond to three weeks of partial immobilization, physical therapy, and factor replacement, prednisone or a similar steroid is given for one week in the appropriate dosage.
Prolonged immobilization of the affected joint should be avoided, as this results in marked muscle atrophy and restriction of joint motion.
Support of the lower limb in orthotic devices is indicated when mechanical insufficiency of the lower limb predisposes the child to fall and sustain repeated injury.
Chronic condition results after repeated acute hemophilic arthropathy. Repeated acute episodes result in intra-articular fibrosis, cartilage destruction, and joint stiffness. This condition is preventable in most cases by effective and immediate treatment of acute hemarthrosis.
In the management of chronic hemophilic arthropathy, physical therapy, traction, orthoses, traction, and surgery play an important role. Treatment needs to be individualized. The objective is to correct joint deformity and to restore function.
Modalities Used in Treatment of Hemophilic Arthropathy
In flexion deformities of the knee and hip, a period of continuous traction is effective in relieving muscle spasm and increasing range of motion. Initially, traction forces are in the line of deformity and are gradually altered to achieve correction.
Prophylactic protection with antihemophilic factor is usually not required while the patient is in traction. Once a neutral or a nearly 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 range of motion of the joints.
As highlighted previously, if a functional range of motion is not achieved after two or three weeks of traction, a wedging cast is applied. The antihemophilic factor is administered when the cast is wedged.
When full joint motion is achieved the knee is immobilized for a period of seven to ten days and maintained in a plastic splint.
Physical therapy in the form of active exercises is begun and increased gradually.
If bleeding occurs during physiotherapy, it is controlled by intravenous administration of antihemophilic factor.
Forceful manipulation of a joint under general anesthesia is not recommended.
If deformities caused by hemarthrosis cannot be corrected by conservative closed methods, surgical correction is indicated. For example, if equinus deformity is very severe and rigid, tendo Achillis lengthening is indicated.
Open surgery has become relatively safe, provided the clotting mechanism is restored to near normal by the administration of antihemophilic factor. This should be continued for three weeks. Sutures should be removed on the fourteenth to sixteenth day postoperatively.
Wounds heal normally in hemophilic patients.
During surgery and the first postoperative day, the factor level should be raised to 100 percent by infusion of factor concentrate. During the first postoperative week, the factor level is maintained at 50 percent, and subsequently for the first postoperative month at 30 to 40 percent by daily infusions of factor concentrate.
Synovectomy is done to prevent progression of hemophilic arthropathy. It helps by
- Decreases the vulnerability to the trauma of the highly vascular synovial tissue i
- Hemophilic synovial tissue has a high level of fibrinolytic activity that tends to prolong the bleeding episodes.
- Hypertrophic synovial tissue in hemophilia contains increased levels of acid phosphatase and cathepsin D.
- Hemosiderin deposition in the synovium interferes with the production of collagenases, which may cause the death of chondrocytes.
Synovectomy is indicated in
- History of severe recurrent hemarthrosis -two or three major bleeding episodes per month
- Patients who fail to respond to aggressive medical management for a period of at least six months.
- Failure of response to orthopedic nonsurgical treatment
- Radiographic Stage II or Stage III hemophilic arthropathy
In stages IV and V, synovectomy is not effective and contraindicated.
Total Joint Replacement
Total joint replacement in bilateral knees is indicated with Stage IV or Stage V arthropathy when persistent knee pain is present.
Total hip replacement is indicated in Stage IV or Stage V hemophilic arthropathy when pain is persistent with a severe disability not relieved by conservative measures. Arthroplasty of the elbow has been reported.
Arthrodesis of the ankle, subtalar and midtarsal joints in the foot, shoulder, or knee may be indicated when these joints are destroyed.