Orthopaedic Surgery - Hemophilia

Basics

Hemophilia is an inherited coagulation-factor deficiency that causes abnormal and prolonged bleeding.

The direct disorder involves the clotting system, but repeated hemorrhage can secondarily affect many organ systems, particularly the joints, muscles, peripheral nerves, and central nervous system.

The age at diagnosis depends largely on disease severity. Severe forms are usually recognized in infancy or early childhood, whereas mild disease may not become apparent until surgery, dental work, or significant trauma.

Classification by Factor Activity

Severity is classified according to the percentage of normal clotting-factor activity.

Severe Hemophilia

Severe disease is defined by <1% normal factor activity.

These patients may experience spontaneous bleeding, particularly into joints and muscles.

Moderate Hemophilia

Moderate disease is characterized by approximately 1–5% factor activity.

Bleeding usually follows relatively minor trauma but may occasionally occur spontaneously.

Mild Hemophilia

Mild disease is associated with >5% factor activity.

Bleeding usually becomes evident only after significant trauma, surgery, or invasive procedures.

Types

Hemophilia A

Hemophilia A, historically called classic hemophilia, results from deficiency or dysfunction of factor VIII.

Hemophilia B

Hemophilia B, historically called Christmas disease, results from deficiency or dysfunction of factor IX.

General Prevention

A major goal of long-term care is prevention of recurrent joint bleeding and development of target joints.

Modern prophylactic factor replacement or other hematologic therapy, together with patient education and appropriate activity modification, can substantially reduce cumulative joint damage.

Epidemiology

The combined frequency of hemophilia has historically been estimated at approximately 1 per 10,000 people, although prevalence varies by population and method of ascertainment.

Males are affected far more commonly because the classic forms are X-linked disorders.

Relative Frequency

Hemophilia A is considerably more common than hemophilia B.

Older series have estimated approximately:

75% hemophilia A, 12% hemophilia B, with the remainder representing other rare coagulation-factor deficiencies.

Risk Factors

The principal risk factor is a positive family history, particularly affected males on the maternal side.

However, new mutations may occur, so absence of a known family history does not exclude the diagnosis.

Genetics

Hemophilia A and B are generally inherited in an X-linked recessive pattern.

Affected males inherit the pathogenic variant through the maternal line, while females are usually carriers, although some carriers can have reduced factor levels and clinically important bleeding.

Etiology

Hemophilia A

Hemophilia A results from a pathogenic variant affecting the F8 gene, leading to factor VIII deficiency.

Hemophilia B

Hemophilia B results from a pathogenic variant affecting the F9 gene, leading to factor IX deficiency.

Diagnosis

Early Presentation

In severe hemophilia, the diagnosis may become apparent during infancy because of excessive bleeding after:

Circumcision, immunizations, oral or lip trauma, venipuncture, or minor falls.

Mild Disease

Patients with milder hemophilia may remain undiagnosed until a major laceration, dental procedure, or operation causes unexpectedly prolonged bleeding.

Recurrent Hemarthrosis

Repeated bleeding into joints is one of the most important long-term manifestations.

The joints most often involved include the:

Knees, ankles, and elbows.

Shoulders may also be affected.

Target Joint

After a joint has bled repeatedly, it becomes increasingly susceptible to additional hemorrhage.

Such a repeatedly affected joint is termed a target joint.

Symptoms of Joint Bleeding

An acute hemarthrosis often begins with deep pain, pressure, or tightness before visible swelling develops.

As blood accumulates, the joint becomes swollen, warm, painful, and increasingly restricted in motion.

Muscle Hemorrhage

Muscle bleeding may cause swelling, pain, loss of motion, and compression of nearby nerves.

Iliopsoas Hemorrhage

An important example is bleeding into the iliopsoas muscle, which may compress the femoral nerve and produce weakness, sensory loss, or femoral neuropraxia.

Chronic Hemophilic Arthropathy

Repeated hemarthroses stimulate synovial hypertrophy and chronic joint damage.

Over years, the affected joint may develop:

Stiffness, flexion contracture, cartilage destruction, subchondral changes, chronic pain, and degenerative arthritis.

Physical Examination

Joint Examination

All major joints should be assessed for:

Effusion, tenderness, warmth, swelling, range-of-motion loss, deformity, and contracture.

Particular attention should be given to the knees, ankles, elbows, and shoulders.

Ankle Examination

An early ankle effusion may be suggested by loss of the normal soft-tissue depressions around the malleoli.

Knee Examination

Knee flexion should be compared bilaterally.

The examiner should also assess whether the patient retains the normal small amount of hyperextension, often approximately 5–10°.

Joint Enlargement

Chronically affected joints may appear enlarged because of:

Synovial hypertrophy, epiphyseal overgrowth related to hyperemia, and atrophy of surrounding muscle.

Bleeding Log

Patients may be encouraged to keep a record of bleeding episodes.

This can help identify development of a target joint and guide prophylactic treatment.

Neurologic Examination

The examiner should look for neurologic sequelae of previous bleeding.

Examples include:

Hemiparesis after intracranial hemorrhage, femoral neuropathy from iliopsoas bleeding, or sciatic neuropathy from deep pelvic or gluteal bleeding.

Laboratory Tests

Factor Assays

Factor VIII or IX activity should be measured and expressed as a percentage of normal activity.

Clinical severity correlates broadly with the residual factor level.

Even relatively low levels, such as approximately 5–10%, may provide substantial protection against spontaneous bleeding compared with severe deficiency.

Inhibitors

If factor activity fails to rise as expected after replacement therapy, a neutralizing inhibitor should be suspected.

An inhibitor is an antibody directed against the replacement clotting factor, most commonly factor VIII.

Surgical Significance of an Inhibitor

The presence of a significant inhibitor complicates hemostatic management and increases the risk of elective surgery.

Procedures should therefore be coordinated with an experienced hematology team.

Additional Long-Term Screening

Historically, patients with hemophilia exposed to plasma-derived blood products were at increased risk for blood-borne infection.

Long-term care should take into account the patient’s status regarding:

Hepatitis, HIV, and factor inhibitors, when clinically relevant.

Pathological Findings

Gross Appearance of the Joint

The synovium of a chronically affected hemophilic joint may appear brown and velvety because of hemosiderin deposition and synovial hypertrophy.

Cartilage Damage

The articular cartilage progressively loses its normal smooth appearance.

Advanced disease may demonstrate erosions and irregular defects.

Microscopy

The synovial lining becomes:

Hypertrophic, hypervascular, and hemosiderin-laden.

The increased vascularity predisposes the joint to further bleeding.

With time, fibrosis develops and contributes to progressive stiffness and loss of motion.

Imaging

Plain radiographs of a hemophilic target joint may demonstrate a progressive sequence of abnormalities.

Early Changes

Initial findings include:

Soft-tissue swelling and periarticular osteopenia.

Intermediate Changes

With recurrent bleeding, radiographs may show:

Epiphyseal enlargement, joint-space narrowing, subchondral irregularity, and cyst formation.

Advanced Changes

Late hemophilic arthropathy resembles severe degenerative joint disease with:

Marked joint-space loss, deformity, subchondral cystic change, and articular destruction.

Differential Diagnosis

Important alternatives include:

Von Willebrand disease, pigmented villonodular synovitis, acquired coagulation-factor inhibitors, and thrombocytopenia.

Treatment

General Principles

Treatment depends on the severity and location of bleeding and should be coordinated closely with hematology.

The principal goals are to:

Stop hemorrhage, prevent recurrent bleeding, preserve joint motion, and avoid long-term arthropathy.

Acute Hemarthrosis

The cornerstone of treatment is prompt clotting-factor replacement or other appropriate hemostatic therapy.

Early treatment limits the amount of blood entering the joint and reduces secondary synovial damage.

Rest and Immobilization

A short period of rest and protective immobilization may be used during the acute painful phase.

Prolonged immobilization should be avoided because it promotes stiffness and muscle wasting.

Range of Motion

Gentle range-of-motion exercises should begin once bleeding and pain have settled.

Joint Aspiration

If a large tense hemarthrosis produces severe pain or threatens joint motion, aspiration may be considered after adequate factor replacement has been established.

The procedure should be performed under sterile conditions with hematologic support.

Compression

Compression and supportive measures may help reduce swelling after bleeding is controlled.

Chronic Hemophilic Synovitis

Repeated bleeding can produce hypertrophic synovium that itself becomes a source of further hemorrhage.

Synovectomy may therefore be considered for persistent target-joint bleeding despite optimized medical treatment.

Synovectomy

Synovectomy removes or ablates diseased hypertrophic synovium in an attempt to reduce recurrent bleeding.

Arthroscopic Synovectomy

In appropriate joints, synovectomy can be performed arthroscopically.

Radiosynovectomy

Injection of a radionuclide into the joint can produce chemical or radiation-induced synovial ablation.

This may reduce bleeding frequency in selected high-risk target joints.

End-Stage Arthropathy

Severely damaged painful joints may require reconstructive surgery.

Arthroplasty

Joint replacement can provide substantial pain relief and improved function, particularly for end-stage knee arthropathy.

Arthrodesis

Fusion may be appropriate for selected end-stage joints, especially the ankle, when painful destruction is severe.

Iliopsoas Hemorrhage

Psoas bleeding associated with femoral neuropraxia is generally treated with:

Hemostatic factor replacement, activity restriction, observation, and serial neurologic examination.

Most cases are managed nonoperatively unless another complication develops.

Compartment Syndrome

Compartment syndrome should be treated according to standard principles.

Because surgery itself carries major bleeding risk, clotting-factor correction should be initiated urgently, followed by decompression when clinically indicated.

Home Prophylaxis

Home treatment programs can substantially reduce the frequency and severity of bleeding episodes.

When the patient and family are appropriately trained, factor or other prescribed hemostatic treatment can be administered promptly at the first sign of bleeding.

Activity

Regular low-impact physical activity is generally beneficial because strong muscles help stabilize joints.

Activities with a high risk of collision or trauma may require modification according to disease severity and hematology guidance.

Physical Therapy

Physical therapy is important for monitoring and maintaining:

Joint range of motion, muscle strength, gait, balance, and overall function.

It is particularly useful after major bleeding episodes or orthopaedic surgery.

Medication

Analgesia

Medications that impair platelet function should generally be avoided unless specifically approved by the treating hematologist.

NSAIDs and Aspirin

Aspirin and many traditional NSAIDs can worsen bleeding because of their antiplatelet effects.

Acetaminophen

Acetaminophen is commonly used for pain control because it does not significantly impair platelet function.

Other analgesic choices should be individualized.

Surgery

Any operation in a patient with hemophilia requires careful perioperative coordination with hematology, including planned factor replacement or other hemostatic therapy before, during, and after the procedure.

Synovectomy

Surgical or radiosynovectomy may be performed for recurrent target-joint bleeding that persists despite adequate prophylaxis.

Total Knee Arthroplasty

Knee replacement may be indicated for severe end-stage hemophilic arthropathy with disabling pain and loss of function.

Ankle Arthrodesis

Fusion can be considered for severe painful ankle degeneration when reconstruction is unlikely to provide reliable function.

Follow-Up

Prognosis

With modern prophylaxis and multidisciplinary care, many patients can maintain substantially better joint function and life expectancy than was historically possible.

Outcome depends on:

Severity of factor deficiency, access to prophylactic treatment, inhibitor development, frequency of bleeding, and established joint damage.

Complications

Neurologic Hemorrhage

Bleeding into the brain or around major peripheral nerves may produce catastrophic neurologic injury.

Intracranial hemorrhage is a medical emergency.

Hemophilic Arthropathy

Repeated hemarthroses can cause:

Joint stiffness, contracture, chronic synovitis, cartilage destruction, and secondary arthritis.

Compartment Syndrome

Deep muscle hemorrhage may increase compartment pressure and threaten nerve and muscle viability.

Peripheral Nerve Compression

Large hematomas can compress nearby nerves, particularly the femoral or sciatic nerve.

Blood-Borne Infection

Historically, transfusion-transmitted hepatitis and HIV were major complications of plasma-derived treatment products.

Modern screening and recombinant therapies have greatly reduced this risk.

Inhibitor Formation

Development of neutralizing antibodies against replacement factor can make bleeding more difficult to control and complicate surgery.

Patient Monitoring

Patients should ideally be followed through a multidisciplinary hemophilia treatment program.

Care commonly involves:

Hematology, orthopaedics, physical therapy or rehabilitation, dentistry, nursing, and social services.

Orthopaedic Monitoring

Follow-up should assess:

Frequency of hemarthrosis, development of target joints, joint range of motion, contractures, muscle strength, gait, pain, and radiographic progression of arthropathy.

Early recognition of recurrent joint bleeding provides the best opportunity to prevent irreversible hemophilic arthropathy.