Musculoskeletal Manifestations of Hemophilia:
Imaging Features
Sriram Jaganathan, MD (Radio-Diagnosis),
Shivanand Gamanagatti, MD (Radio-Diagnosis), and Ankur Goyal, MBBS
The purpose of this pictorial assay is to demonstrate the
imaging features of the various musculoskeletal manifestations of hemophilia, an X-linked disorder. Depending on the
site of recurrent bleeding, musculoskeletal manifestation can
be in the form of hemophilic arthropathy and/or soft tissue,
intraosseous, or subperiosteal pseudotumors. Radiography,
sonography, computed tomography, and especially magnetic
resonance imaging help in the evaluation of hemophilic
arthropathy and pseudotumors, providing accurate diagnosis, thus avoiding inadvertent procedures and related complications. Treatment includes replacement of clotting factors
either continuously or when indicated, radionuclide or open
synovectomy in cases of disabling arthropathy.
Introduction
Hemophilia is an X-linked recessive disorder that
occurs because of deficiency of clotting factors. The
disease occurs predominantly in males and is transmitted through females. The two common forms of
this disorder, hemophilia A and B (due to the deficiency of clotting factor VIII and IX, respectively), are
similar in their clinical presentation and imaging
findings. The classic presentation is bleeding into the
joints leading to hemophilic arthropathy. Other locations of bleeding include soft tissues, subperiosteum,
and within the bone, the latter two being rare. The
radiographic features of these lesions may mimic
many tumor and tumor-like conditions (hence called
pseudotumors) and are not diagnostic. However, hemophilic pseudotumors should be kept in the differential diagnosis of well-defined osseous expansile lytic
From the Department of Radiodiagnosis, All India Institute of Medical
Sciences, New Delhi, India.
Reprint requests: Shivanand Gamanagatti, Room Number 66, Department
of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi110,029, India. E-mail: [email protected].
Curr Probl Diagn Radiol 2011;40:191-197.
© 2011 Mosby, Inc. All rights reserved.
0363-0188/$36.00 ⫹ 0
doi:10.1067/j.cpradiol.2010.08.001
Curr Probl Diagn Radiol, September/October 2011
FIG 1. Fourteen-year-old boy with hemophilia presented with swelling of
right knee. Anteroposterior (A) and lateral radiographs (B) show widening
of the intercondylar notch (arrowhead), epiphyseal overgrowth and
osteopenia, destruction of the articular surface (black arrow), and associated soft-tissue swelling (asterisk) involving the right knee joint. Left knee
joint is normal. These features are diagnostic of hemophilic arthropathy.
lesion(s) in a young male, especially in the presence of
adjacent hemophilic arthropathy. The presence of
various stages of hemorrhage surrounded by hemosiderin/sclerotic rim, appreciated on magnetic resonance
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FIG 2. Sixteen-year-old male with hemophilic arthropathy. Axial gradient echo MR images (A, B) of the right knee joint show hypointense areas
with blooming involving the femoral attachment sites of anterior and posterior cruciate ligaments (asterisk). The hypertrophied synovium (white
arrow) also shows blooming. These hypointense areas with blooming represent hemosiderin deposition due to repeated hemarthrosis in a
hemophilic patient. Sagittal gradient echo MR images (C, D) show hypointensity associated with blooming artifact involving the anterior cruciate
ligament (white arrow) and posterior cruciate ligament (black arrow), suggesting hemosiderin deposition. Note, associated joint effusion is seen.
(MR) imaging, points toward this diagnosis. In this
pictorial assay, we intend to describe the various musculoskeletal manifestations of hemophilia with an emphasis
on the characteristic imaging appearance on conventional
radiograph, ultrasound, and MR imaging.
Hemophilic Arthropathy
Hemorrhage in hemophilic patients occurs most commonly in the musculoskeletal system, although it can
occur anywhere. In the musculoskeletal system, joints
are the most common site of bleeding followed by soft
tissues and bones.1-4 Recurrent bleeds are common
into the synovial joints and result in articular and
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periarticular abnormalities.5-7 The usually affected
joints are knee, ankle, elbow, shoulder, and hip in
descending order of frequency.8 Early findings include
joint effusion and hemarthrosis, followed by articular
and periarticular changes (including synovial hypertrophy and hemosiderin deposition). In later stages,
there is epiphyseal overgrowth and osteopenia (due to
hyperemia), early closure of physeal plate, destructive
changes like loss of cartilage, subchondral cyst formation, and bone erosions.7 Features that favor hemophilic arthropathy on radiograph include epiphyseal
overgrowth and osteopenia, widened intercondylar
notch, soft-tissue swelling, flattening of the condylar
surface, squaring of the patella, and other destructive
Curr Probl Diagn Radiol, September/October 2011
FIG 3. Twenty-five-year-old hemophiliac presented with difficulty in walking and joint pain involving both knees. Anteroposterior radiograph of both
knees (A) shows multiple expansile lytic lesion involving the right proximal tibia (white arrow), left distal femur (black arrowhead), and left proximal tibia
(black arrow). Multiple osseous trabeculae (asterisk) are seen extending across the lesion in left proximal tibia. The same lytic lesion (white arrowhead)
of the right proximal tibia is seen on lateral projection (B). Note, distal femoral lesion also shows pathologic fracture and associated soft-tissue swelling.
FIG 4. MR images of the same patient as in Fig 3. T1-weighted coronal MR image (A) shows well-defined hypointense lesion admixed with areas
of hyperintensity (asterisks) in right proximal tibia (black arrow), left distal femur (black arrowhead), and left proximal tibia (white arrow). On
T2-weighted coronal MR images, non-fat-suppressed (B) and fat-suppressed (C), these lesions are heterogeneously hyperintense with hypointense
areas within suggestive of blood breakdown products in various stages (white arrowheads). Note, a thin hypointense rim is seen around in all the
lesions on T2-weighted MR images, suggesting hemosiderin/sclerotic rim.
changes, as mentioned above (Fig 1). The radiographic
mimic of hemophilic arthropathy is juvenile rheumatoid arthritis. The classical features on MR imaging
include hemosiderin deposition (seen as hypointense foci
on both TI-weighted and T2-weighted sequences, and
showing blooming on gradient echo sequences) and
synovial hypertrophy (best appreciated on T2-weighted
fat-suppressed and postgadolinium T1-weighted sequences) (Fig 2). Hemosiderin may be deposited along
the intra-articular ligaments and tendons as well (Fig 2).
Cartilage is well evaluated on fat-suppressed proton
Curr Probl Diagn Radiol, September/October 2011
density sequence or on dual echo steady-state sequence7
and thus MR imaging can pick up cartilage destruction
and bone erosions at an early stage. MR imaging optimally demonstrates intra-articular blood products, synovial hypertrophy, and effusion and this information is
instrumental in early treatment planning.9-11
Hemophilic Pseudotumor
Pseudotumors are rare complication of hemophilia,
occurring in 1%-2% of the patients with severe coag-
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FIG 5. Anteroposterior (A) and lateral radiographs (B) of the left knee of the same patient as in Fig 3 show large soft-tissue mass in subperiosteal
location in the posterior aspect of left distal femur, with peripheral curvilinear calcific strut (arrow). Note the high density of the mass relative to
the surrounding soft tissues. Note is also made of pathologic fracture (arrowhead) involving the intraosseous pseudotumor in left distal femoral
metaphysis. Sagittal T2-weighted MR images (C, D) show subperiosteal location of the pseudotumor in posterior aspect of left distal femur with
T2-hypointense rim (arrowheads), suggestive of hemosiderin deposition. Note the heterogeneous signal intensity with the presence of both hypoand hyperintense areas, suggestive of the presence of various stages of hemorrhage within. Note is also made of intraosseous pseudotumor in
proximal tibial metaphysis with similar signal characteristics.
ulation disorder.12,13 A hemophilic pseudotumor is a
chronic, encapsulated, slowly expanding mass lesion
occurring because of recurrent hemorrhage into the
extra-articular musculoskeletal system. It may arise
because of minor trauma or de novo. Usually these are
painless expanding masses that may be detected incidentally. These may also present due to acute bleeding,
which causes local and systemic signs or secondary
complications (fracture or neurovascular compression).
These may result in contractures and compartment
syndromes, leading to profound loss of function.
Superimposed infection, fistula formation to skin or
bowel, and exsanguination due to pseudotumor rupture may complicate disease management.13,14 Although they may not be limited by anatomical boundaries, they are categorized into osseous and soft-tissue
lesions.8 The imaging characteristics on various modalities depend on the site and extent and stage of
bleeding.15 A pseudotumor consists of blood products
in various stages of evolution and has a fibrous capsule
that contains hemosiderin.16
Just as repetitive bleeding into the joints leads to
hemophilic arthropathy, recurrent bleeding into the
bones results in osseous pseudotumor (intraosseous/
intramedullary and subperiosteal). The most frequently
implicated bones are femur, pelvis, tibia, and small bones
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of the hand in order of descending frequency.8 On
radiograph, intraosseous pseudotumors appear as welldefined, unilocular or multilocular, expansile lytic lesions
of variable size with geographic pattern of bone destruction (Fig 3). Osseous trabeculae or septa-like structures
frequently extend across the osteolytic lesions (Fig 3).
These can occur in any portion of the tubular bones,
may be intramedullary or eccentric, and may show
endosteal scalloping, cortical thinning, peripheral sclerosis, as well as dystrophic calcification. These lesions
can be quite destructive and completely replace the
involved segments of bone. Deformities and pathologic fractures may occur due to progressive expansion of the bone (Fig 3). The various radiographic
differentials that merit consideration are primary and
secondary bone neoplasms (giant cell tumor, plasmacytoma, telangiectatic osteosarcoma, metastasis, and
malignant fibrous histiocytoma), tumor-like lesions
(aneurysmal bone cyst, brown tumor, solitary bone
cyst), and infection (echinococcosis).17 Computed tomography (CT) helps by better depicting crossing
trabeculae, cortical change, periosteal reaction, and
anatomical extent. MR imaging has the characteristic
appearance of a multiloculated lesion containing fluid
components having heterogeneous signal intensity on
various sequences, reflecting the presence of blood
Curr Probl Diagn Radiol, September/October 2011
FIG 6. Twenty-four-year-old male with hemophilia presented with swelling in the right gluteal region. Anteroposterior radiograph of the pelvis (A)
with a magnified image (B) shows increased soft tissue in the right gluteal location (asterisk). Grayscale and color Doppler sonography (C, D)
images of the right gluteal location show an intramuscular heterogenous lesion predominantly hypoechoic (black arrow). There is no vacularity
(white arrow) within the lesion. These features suggest intramuscular pseudotumor in a hemophilic patient. (Color version of figure is available
online.)
FIG 7. Thirty-year-old hemophilic patient presented with swelling in the left hip region. Axial contrast-enhanced CT images (A, B) show
heterogenous lesion (arrows) with peripheral enhancement involving the proximal left thigh with nonenhancing areas (asterisk) within. Note,
variable attenuation areas are seen in the lesion, suggesting various stages of hemorrhages in a soft-tissue pseudotumor.
products in various stages of evolution15 (Fig 4).
Fat-suppressed T1-weighted images depict methemoglobin and gradient echo images show areas of hemosiderin deposition. The lesions are surrounded by T1and T2-hypointense rim (Fig 4), which is due to either
hemosiderin or peripheral sclerosis/fibrous capsule or
residual cortical bone, and shows thin nodular enhancement (if any) on postgadolinium images. MR
imaging accurately assesses intramedullary and softtissue extension, neurovascular involvement, as well
Curr Probl Diagn Radiol, September/October 2011
as monitoring the therapeutic response. Fluid–fluid
levels may also be seen on MR imaging.17 Subperiosteal pseudotumors result because of elevation of the
periosteum and pressure necrosis of the bone, caused
by hemorrhage. Radiographic findings include softtissue mass in subperiosteal location, cortical erosions,
subperiosteal new bone formation, and soft-tissue
extension (Fig 5). These lesions may be associated
with aggressive periosteal reaction. The presence of
curvilinear calcific struts at the periphery, projecting into
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FIG 8. Twenty-six-year-old male, with a known case of hemophilia, presented with pain, swelling, and discharging sinus in the left ankle region.
Lateral radiograph (A) of left ankle shows diffuse sclerosis of calcaneum with central lytic region (arrow). Coronal MR images of left ankle show
diffuse hypointensity of calcaneum on T1-weighted (B) and hyperintensity on T2-weighted (C) images. Note is made of a central hypointense focus
(arrow) on both T1- and T2-weighted images, suggesting air within (on correlating with history of discharging sinus and lytic appearance on
radiograph). Sagittal T2-weighted MR image of left ankle shows hyperintense areas in talus, navicular, and other carpal bones representing
marrow edema (D). These features suggest chronic osteomyelitis in a intraosseous pseudotumor.
soft tissues, is the most characteristic feature of hemophilic pseudotumors18 (Fig 5). On CT and MR imaging,
hemorrhagic lesions may be confined to the subperiosteal
space or extend into the bone or soft tissue.
Recurrent and nonresolving soft-tissue bleeding
gets organized and causes joint contractures and softtissue pseudotumors. The latter are most common in
the thigh, gluteal region, and iliopsoas muscle.19
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Soft-tissue pseudotumors can be categorized into intramuscular or extramuscular (interfascial, subcutaneous).14
Intramuscular hematomas usually remain localized, although they may produce pressure deformity or subperiosteal new bone formation. Pressure to adjacent soft
tissues may lead to skin necrosis, pain, neurologic deficits, and restriction of movement. On radiographs, softtissue pseudotumors manifest as increased soft-tissue
Curr Probl Diagn Radiol, September/October 2011
density, with or without internal calcification (Fig 6).
Adjacent bony structures may show focal new bone
formation, extrinsic erosion, periosteal reaction, or
medullary destruction. Secondary infection is rare and
is suggested by the presence of gas within. Sonography helps to follow the progression or regression of
hematoma after therapy. Depending on the different
stages of the hemorrhagic event, variable patterns of
echogenicity on ultrasound (anechoic or heterogeneously hypoechoic) and attenuation on CT (high,
isodense, or low) may be seen.20 No internal vascularity is seen on color Doppler imaging (Fig 6).
Contrast-enhanced CT shows peripheral enhancement
and central nonenhancing variable attenuation areas
(Fig 7). MR appearance is similar to the osseous
pseudotumor, demonstrating blood products in various
stages of evolution18 and hemosiderin rim.
Hemophilic pseudotumors may be complicated by
superimposed infection, pathologic fractures, and fistula formation (Figs 3, 5, and 8).
Hemophilic pseudotumors may develop in soft
tissues, in the bone, or in subperiosteum, in descending order of frequency and may coexist in these
locations. The radiographic appearance is variable and
has many differential diagnoses. MR imaging is superior for demonstrating different stages of hemorrhage,
hemosiderin/sclerotic rim, and in displaying the soft
tissues and intramedullary spaces. Accurate knowledge of the extent and character of pseudotumors
gained through sonography, CT, and especially MR
imaging is extremely valuable for optimal management. Apart from the clinical profile of recurrent
bleeding, the presence of hemophilic arthropathy near
the pseudotumor is frequent on conventional radiographs
and serves as an important diagnostic clue, thus differentiating this entity from other mimickers. It is vital to
make the diagnosis of hemophilic pseudotumor because
percutaneous drainage or biopsy is contraindicated due to
the risk of complications, including life-threatening
bleeding, fistula formation, and infection.
Conclusions
Hemophilia, a bleeding disorder with X-linked inheritance, can present with varied musculoskeletal manifestation. A proper knowledge of the imaging appearances is essential for early diagnosis. Although many
conditions may mimic hemophilic lesions, clinical
details along with imaging features can narrow down
Curr Probl Diagn Radiol, September/October 2011
the differential diagnoses. Early diagnosis is useful in
planning therapy, such as synovectomy, radiosynarthroses, and/or prophylactic factor therapy.
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