A 36-year-old man with known hemophilia presented with pain and swelling of his left knee. Three days earlier he had fallen onto the same knee. The physical examination revealed a grossly swollen and tender knee.
cHe denied illicit drug use or any recent fevers or chills.
Radiographs of the left knee at that time were significant only for
a joint effusion (not shown). He was given nonsteroidal
anti-inflammatory medication and was referred to physical therapy
for range-of-motion (ROM) exercises and modalities for pain and
swelling control. Although the pain and swelling gradually
decreased over a 4-week period, the patient experienced progressive
loss of motion and represented 10 months later with significant
joint contractures. Repeat radiographs (Figure 1) were obtained,
followed by magnetic resonance (MR) imaging of the left knee
Radiographs of the right knee were normal. The radiographic
images of the left knee reveal extensive erosive and degenerative
change about the femoral-tibial and femoral-patellar joints and
diffuse, severe osteopenia (Figure 1). MR imaging shows extensive
subchondral cystic change and edema. The T2-weighted MR image
shows, particularly well, multiple, intra-articular dark irregular
foci corresponding to hemosiderin deposits (Figure 2).
The coagulation dysfunction in hemophilia A is a sex-linked
deficiency or abnormality of a plasma protein called factor VIII
(FVIII) found in 1 of 5000 male births. Physiologically, FVIII is
found circulating in the plasma bound to von Willebrand's factor,
which acts as a carrier protein. The degree of FVIII deficiency
correlates with the extent of bleeding, and hemophilia A can be
classified as severe (<1% activity), moderate (1% to 5%), or
mild (5% to 25%). Typically, symptoms begin in childhood associated
with hemorrhage after minor trauma. As the individual ages and
becomes more prudent, symptoms become less frequent. Although a
presumptive diagnosis can be made based on age, sex, family
history, and clinical presentation, the presentation is not always
classic. Up to 30% of patients may have a normal family history due
to mild disease or lack of males in the family tree. Mild disease,
however, may not present until well into adulthood; there has even
been a case in which the patient was diagnosed during his 60s.
Hemophilia has been well documented in females in whom X chromosome
inactivation occurs at an early stage of embryogenesis, resulting
in unusually low levels of FVIII.
The differential diagnosis for congenital bleeding disorders
includes hemophilia B (deficiency of factor IX), factor XI
deficiency, and von Willebrand's disease (deficiency of vWF).
Acquired coagulation disorders should also be considered, such as
vitamin K deficiency, liver disease, and factor deficiencies that
may be seen in conditions like systemic lupus erythematosus or
Radiographically, the diagnosis is often suggested by recurring
changes of hemarthrosis in the knees, elbows, and ankles.
Although there is no universally accepted classification system,
several common patterns of joint disease in hemophilic arthropathy
have been described by Arnold and Hilgartner.
The initial episode of intra-articular bleeding, often following
minor trauma, is usually associated with joint effusion without
osseous or articular involvement. With recurrent small bleeds or
after a large bleed, peri-articular osteoporosis and regional
soft-tissue swelling are common sequelae. In adolescents, the
hyperemic joint may lead to localized, accelerated growth and
limb-length discrepancies. Eventually osseous irregularity and
erosion develop, accompanied by subchondral cysts. Synovial
effusions are common and may appear radiodense due to hemosiderin
deposition. An important diagnostic clue to hemophilic arthropathy
during this phase is the preservation of joint space. As osseous
erosions continue, however, joint space narrowing is seen,
associated with progressive, symmetric cartilaginous destruction.
Eventually, complete obliteration of the joint space will occur and
secondary degenerative signs, including osteophytes and eburnation,
develop. With chronic disease, muscle imbalances and joint
contractures may develop.
MR imaging can detect early erosions not visualized on
conventional radiography and is probably the best modality for
assessing intra-articular abnormalities associated with hemophilic
arthropathy. Generally, hemarthrosis can be seen as areas of low to
intermediate signal on T1-weighted MR images and increased signal
on T2-weighted MR images.
Chronic peri-articular changes are often visualized as decreased
signal intensity on both T1- and T2-weighted MR images. Synovial
hypertrophy results from fibrosis and appears as nodular areas of
low to intermediate signal intensity on T1- and T2- weighted MR
images. Subchondral cysts containing inflammatory fluid show
increased signal on T2-weighted MR images, while fibrotic cysts are
Because articular cartilage is well visualized on MR imaging, focal
areas of thinning or absent cartilage can be easily detected.
Treatment for hemophilia typically involves some form of factor
replacement depending on the severity of the disease. The pain and
swelling associated with joint injuries can be treated with
conservative measures such as immobilization, cooling, and
nonsteroidal anti-inflammatory medication, which do not interfere
with the coagulation pathway or platelet function. Aspiration
therapy is contraindicated unless necrosis, due to joint tension or
compartment pressure, is imminent. Radiotherapy for vascular
sclerosis can be useful in the treatment of soft-tissue masses and
acute joint hemarthrosis. When irreversible osseous and
cartilaginous changes have occurred, and pain and joint
contractures limit activities of life, joint replacement should be
Hemophilic arthropathy is a rare joint-destroying disorder that
is more prevalent before adulthood. A wide spectrum of radiographic
and MR changes are possible depending on the stage of the disorder.
Correlating a good history with characteristic imaging findings can
result in prompt diagnosis and treatment and may prevent, or at
least delay, the need for joint replacement.
Michael W. Matchette, MD
from the University of Texas Health Science Center, San Antonio,
Justin Q. Ly, MD
from Wilford Hall Medical Center, San Antonio, TX.