eMedicine Specialties > Radiology > Musculoskeletal

Hemophilia, Musculoskeletal Complications

Author: Ray F Kilcoyne, MD, † Former Professor Emeritus, Department of Radiology, University of Colorado Health Sciences Center
Contributor Information and Disclosures

Updated: Mar 21, 2008

Introduction

Background

Hemophilia is the oldest known bleeding disorder. This condition first came to public attention when the disease appeared in the offspring of Queen Victoria of England.¹ Presumably, hemophilia occurred in Queen Victoria's children because of a mutation in one of the queen's X chromosomes. Then, close intermarriages between European royalty caused the disease to spread from the English royal families to the German, Spanish, and Russian royal families in the 19th and 20th centuries. At the time, the mechanism for the bleeding was not known. However, in 1868, the physician Volkmann defined the role of hemorrhage in the pathogenesis of the articular findings in hemophilia.²

• Hemophilia was common in the royal families of Europe because of close intermarriage, beginning with the offspring of Queen Victoria.
• The last Czar of Russia, Nikolas II, had one son, the heir to the throne, Alexis, who had hemophilia.¹ Alexis was a constant source of concern for the royal parents such that worry over his poor health may have contributed to deterioration of the state of the country and the overthrow of the monarchy at the time of the Bolshevik revolution. Prince Alexis, along with his parents and siblings, was later executed at the time of the revolution.

Patient Education

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Hemophilia.

Related eMedicine topics:
Hemophilia, Type A
Hemophilia, Type B
Hemophilia C
Hemophilia, Acquired

Related Medscape topics:
Hard-to-Control Bleeding Disorders
Hepatitis C Seems Milder in Patients With Hemophilia

Pathophysiology

The deficiency or absence of either of 2 clotting elements — factor VIII or factor IX — leads to the clinical condition described as hemophilia A or hemophilia B, respectively. Hemophilia B was formerly known as Christmas disease and is not described in this article; in this condition, life-threatening bleeding into the head or the abdomen may occur at any age.

People with one of these bleeding disorders are prone to have recurrent episodes of hemorrhage into the joints. Acute bleeding increases the pressure in the synovial cavity and bone marrow, which leads to severe pain and possibly osteonecrosis or a pseudotumoral mass. Intra-articular bleeding produces a direct chemical effect on the synovium, cartilage, and bone. Over time, the blood becomes deposited in the form of hemosiderin in these tissues. Recurrent hyperemia of the joint in the growing child causes juxta-articular osteoporosis and overgrowth of the epiphysis.

Roosendaal and Lafeber studied the pathogenesis of the joint changes in both experimental and clinical cases of hemophilia.³ The authors found that the articular cartilage is sensitive to the presence of blood and that damage may occur to the cartilage independent of the synovial changes caused by bleeding. However, practically speaking, the imaging changes that appear first are effusion and synovial proliferation. Damage to the bone and articular cartilage appears later.

Frequency

United States

An estimated 20,000 persons have hemophilia A, which accounts for 75% of all cases of hemophilia in the US (see eMedicine topic Hemophilia, Overview). Women are rarely affected; however, homozygous disease has been reported in females, as well as in patients with Turner (XO) syndrome (see Images 1-2).

International

Hemophilia affects all races and has been reported in all parts of the world. The World Federation of Hemophilia and philanthropic groups have attempted to aid families with this condition who live in developing countries. Current descendents of the royal families in England and Spain appear to be free of either the disease or the female-carrier state.

Mortality/Morbidity

The severity of hemophilia varies.

• Beginning in the early 1980s and continuing to the present, acquired immunodeficiency syndrome (AIDS) has been a significant complication of hemophilia. The use of plasma-derived factor replacement from pooled plasma sources led to 50% of hemophiliacs developing AIDS in the 1980s (see eMedicine topic Hemophilia, Overview). Once the risk of transfusion-related human immunodeficiency virus (HIV) transmission was recognized, the prevalence of new cases of AIDS in hemophiliac patients decreased to nearly zero. Screening for HIV products in blood is effective, but there is still concern that other agents, such as hepatitis A, parvovirus, and the prions that cause Creutzfeldt-Jakob disease, can be transmitted through blood transfusions. In developed countries, recombinant factor VIII is produced synthetically without blood products; this development has allayed fears of some types of disease transmission by eliminating the need for human plasma transfusions.
• See also Clinical Details.

Race

No racial predilection exists for hemophilia.

Sex

Hemophilia is a disease almost exclusively of males because the defective gene is found on the X chromosome.

• The 2 sex-linked disorders (ie, hemophilia A and hemophilia B) become clinically apparent in males, and females are generally asymptomatic carriers.
• Hemophilia is so rare in females that another cause of unexplained or problematic bleeding should be considered before this condition. For example, a traumatic effusion or pigmented villonodular hyperplasia is more likely than hemophilia as an etiology for a bleeding disorder in a female.

Age

• Bleeding into target joints (the joints that are most commonly affected with repetitive bleeding in an individual patient) starts before the age of 2 years and persists into adolescence.
• In some patients, bleeding continues into adulthood, even affecting new target joints after the age of 30 years; however, this occurrence is unusual.
• The late sequelae of joint hemorrhage appear in adolescence or adulthood as a joint deformity, contracture, and/or degenerative arthritis.

Anatomy

Imaging tests such as plain radiography or magnetic resonance imaging (MRI) are helpful in defining the degree of joint destruction. The stages of altered anatomy are defined by classification systems that have been developed for plain radiographs and MRI.^4,5,6 The pathologic-anatomic appearance progresses from joint hemorrhage to joint effusion; synovial hyperplasia; hemosiderin deposition in the synovium, cartilage, and bone; osteoporosis; erosion of subchondral bone; bone cysts; articular cartilage destruction; overgrowth of the epiphysis; joint contracture; and degenerative arthritis.

Presentation

About 70% of patients who have hemophilia are affected with the severe form of the disease and have less than 1% of the normal clotting factor.⁷  Bleeding in these patients occurs spontaneously or after minor trauma. In milder cases of hemophilia, a major bleeding event occurs only after significant trauma or major surgery.

One common presentation is the development of uncontrollable hemorrhage after routine postnatal circumcision in affected male infants. In addition to bleeding into the joints, spontaneous or posttraumatic bleeding may occur in the gastrointestinal or genitourinary tract. Subdural or intracerebral bleeding may be life threatening. Retroperitoneal bleeding may be occult and result in a significant decrease in the patient's hematocrit level.

Hemarthrosis occurs in 75-90% of patients with hemophilia. Young children and adolescents are more likely to bleed into joints than adults are; this may be because adults are better able to protect their joints from trauma. Bleeding occurs in predictable patterns, affecting some joints more than others. The most common target joints are the knee, ankle, and elbow.

The disease tends to be asymmetric in its involvement. Approximately 50% of patients with hemophilia develop permanent changes in the joint. These chronic changes include thick synovial deposition, richly laden with hemosiderin. The synovial masses erode the juxta-articular cartilage and the subchondral bone (see Image 3). Invasion into the bone substance produces intraosseous cyst formation. Bleeding into the bone may rarely produce large, vacuolated spaces that are referred to as intraosseous pseudotumors. Similar blood masses may occur in the cortex and the soft tissues (see Image 7).

Knee involvement

The knee is the classic target joint. Involvement of this joint is most commonly described in the literature and is the basis for the findings described in the Arnold-Hilgartner classification (see the Table below).

The chronic joint effusions in hemophilia may be denser than other effusions because of the presence of iron. Juxta-articular osteoporosis develops, especially in children, secondary to the hyperemic state. The irregular appearance of the subchondral surface is secondary to either blood that directly destroys bone or to synovial intrusion.

Deeper invasion of the synovium and joint fluid leads to multiple subchondral cysts. Chronic hyperemia causes overgrowth of the epiphysis and widening of the intercondylar notch in the growing child. Squaring of the inferior pole of the patella (seen in 20-30% of patients with hemophilia) is another form of overgrowth. A similar effect of overgrowth may be seen in children with juvenile rheumatoid arthritis (JRA). A fixed flexion deformity and painful limitation of motion are late findings on physical examination.

Open table in new window

Ankle involvement

Findings similar to those in the knee also develop in the ankle. With increased screening for joint abnormalities as part of an aggressive treatment regimen for patients with hemophilia, investigators have found that the ankle is more commonly involved as a target joint than the knee. The overgrowth pattern in the ankle leads to a condition called talar tilt, which is a tibiotalar slanting that is due to relative undergrowth of the lateral side of the tibial epiphysis and that leads to a pronated foot position. MRI shows the extension of ankle effusion-synovitis into the subtalar joint (see Image 8).

Elbow involvement

A radiopaque effusion is more easily seen on radiographs in the elbow than in the knee or ankle (see Image 11). The trochlear notch may be widened. Enlargement of the radial head and limited elbow motion are present in advanced cases.

Hip involvement

The hip is not commonly a target joint, but because of the way the blood supply reaches the femoral head, osteonecrosis may occur after intra-articular bleeding does. Osteonecrosis may also occur in the shoulder or ankle (see Image 12). Severe osteoporosis and spontaneous hip dislocation may develop. This distribution in the hips, shoulders, and ankles is probably related to the way the vascular supply enters the joint capsule and nourishes the underlying epiphysis.

Wrist involvement

Wrist-joint deformity may occur from synovitis, but clinical wrist involvement is more common in JRA than in hemophilia.

Shoulder involvement

As in the hip joint, osteonecrosis may occur in the shoulder joint (see Image 14).

Preferred Examination

Plain radiographic classification systems for describing the clinical progression of arthropathy were developed in the 1970s. However, radiographs may lead to the underestimation of soft-tissue changes that precede bone destruction. Treatment of patients with hemophilia at an early age may prevent progression to the later, destructive changes seen on radiographs.

MRI has played a major role in defining such destructive soft-tissue changes and has led to early, aggressive treatment of affected patients with factor prophylaxis or replacement.⁴ Overall, the best imaging modality is MRI because this technique combines excellent spatial resolution with the ability to detect soft-tissue bleeding at an early stage. In a given case, all of the other mentioned imaging modalities may play a role, but the first choice is MRI.

Ultrasonography offers an appealing alternative for assessing the joint fluid and synovial proliferation. This technique has been used more extensively in Canada and Europe than in the United States.⁸

Limitations of Techniques

As mentioned above (see Preferred Examination), plain radiographs cannot clearly depict soft-tissue changes. In early hemophilic disease, radiographs may not be needed at all. MRI is the best technique for detecting soft-tissue changes, but it is expensive, and 10% of patients are too claustrophobic to undergo the examination. In addition, some patients' implanted devices, such as pacemakers, preclude MRI evaluation. MRI may not be warranted when the radiographic findings already show advanced disease.

Differential Diagnoses

Ankle, Fractures
Avascular Necrosis, Femoral Head
Elbow Trauma, Pediatric
Juvenile Rheumatoid Arthritis
Pigmented Villonodular Synovitis

Other Problems to Be Considered

• Trauma, scurvy, myeloproliferative disease, and anticoagulant overdose may cause acute hemarthrosis.
• Over time, JRA causes joint deformities in a pattern that is similar to that of hemophilia.
• Pigmented villonodular synovitis (PVNS) produces hemosiderin deposition in the synovium similar to that of hemophilia.
• Synovial hemangiomas may look like hemorrhagic synovitis.²

• Search for CME/CE on This Topic »

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• Hemophilia, Acquired (Hematology)
• Hemophilia, Type B (Emergency Medicine)

• Hemophilia Causes
• Blood and Lymphatic System Center
• Hemophilia Overview
• Hemophilia Symptoms
• Hemophilia Treatment

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