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 manifesta-
tions 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 diagno-
sis, thus avoiding inadvertent procedures and related compli-
cations. 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 trans-
mitted through females. The two common forms of
this disorder, hemophilia A and B (due to the defi-
ciency 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 loca-
tions 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, he-
FIG 1. Fourteen-year-old boy with hemophilia presented with swelling of
mophilic pseudotumors should be kept in the differ- right knee. Anteroposterior (A) and lateral radiographs (B) show widening
ential diagnosis of well-defined osseous expansile lytic of the intercondylar notch (arrowhead), epiphyseal overgrowth and
osteopenia, destruction of the articular surface (black arrow), and asso-
ciated soft-tissue swelling (asterisk) involving the right knee joint. Left knee
From the Department of Radiodiagnosis, All India Institute of Medical joint is normal. These features are diagnostic of hemophilic arthropathy.
Sciences, New Delhi, India.
Reprint requests: Shivanand Gamanagatti, Room Number 66, Department
of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi-
110,029, India. E-mail: shiv223@rediffmail.com. lesion(s) in a young male, especially in the presence of
Curr Probl Diagn Radiol 2011;40:191-197.
adjacent hemophilic arthropathy. The presence of
© 2011 Mosby, Inc. All rights reserved.
0363-0188/$36.00 ⫹ 0 various stages of hemorrhage surrounded by hemosid-
doi:10.1067/j.cpradiol.2010.08.001 erin/sclerotic rim, appreciated on magnetic resonance

Curr Probl Diagn Radiol, September/October 2011 191

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 muscu-
loskeletal 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 com-
monly 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
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 hyper-
trophy 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 forma-
tion, and bone erosions.7 Features that favor hemo-
philic 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

192 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 rheuma-
toid 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 se-
quences) (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
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 opti-
mally demonstrates intra-articular blood products, syno-
vial 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-

Curr Probl Diagn Radiol, September/October 2011 193

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 hypo-
and 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 of the hand in order of descending frequency.8 On

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 inci-
dentally. 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 rup-
ture may complicate disease management.13,14 Al-
though they may not be limited by anatomical bound-
aries, they are categorized into osseous and soft-tissue
lesions.8 The imaging characteristics on various mo-
dalities 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
radiograph, intraosseous pseudotumors appear as well-
defined, unilocular or multilocular, expansile lytic lesions
of variable size with geographic pattern of bone destruc-
tion (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 scle-
rosis, as well as dystrophic calcification. These lesions
can be quite destructive and completely replace the
involved segments of bone. Deformities and patho-
logic fractures may occur due to progressive expan-
sion of the bone (Fig 3). The various radiographic
differentials that merit consideration are primary and
secondary bone neoplasms (giant cell tumor, plasma-
cytoma, telangiectatic osteosarcoma, metastasis, and
malignant fibrous histiocytoma), tumor-like lesions
(aneurysmal bone cyst, brown tumor, solitary bone
cyst), and infection (echinococcosis).17 Computed to-
mography (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

194 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 methemo-
globin and gradient echo images show areas of hemo-
siderin deposition. The lesions are surrounded by T1-
and T2-hypointense rim (Fig 4), which is due to either
hemosiderin or peripheral sclerosis/fibrous capsule or
residual cortical bone, and shows thin nodular en-
hancement (if any) on postgadolinium images. MR
imaging accurately assesses intramedullary and soft-
tissue extension, neurovascular involvement, as well
as monitoring the therapeutic response. Fluid–fluid
levels may also be seen on MR imaging.17 Subperios-
teal pseudotumors result because of elevation of the
periosteum and pressure necrosis of the bone, caused
by hemorrhage. Radiographic findings include soft-
tissue 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

Curr Probl Diagn Radiol, September/October 2011 195

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 hemo-
philic 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 soft-
tissue pseudotumors. The latter are most common in
the thigh, gluteal region, and iliopsoas muscle.19
Soft-tissue pseudotumors can be categorized into intra-
muscular or extramuscular (interfascial, subcutaneous).14
Intramuscular hematomas usually remain localized, al-
though they may produce pressure deformity or subpe-
riosteal new bone formation. Pressure to adjacent soft
tissues may lead to skin necrosis, pain, neurologic defi-
cits, and restriction of movement. On radiographs, soft-
tissue pseudotumors manifest as increased soft-tissue

196 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. Sonogra-
phy 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 heteroge-
neously hypoechoic) and attenuation on CT (high,
isodense, or low) may be seen.20 No internal vascu-
larity 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 fis-
tula formation (Figs 3, 5, and 8).
Hemophilic pseudotumors may develop in soft
tissues, in the bone, or in subperiosteum, in descend-
ing order of frequency and may coexist in these
locations. The radiographic appearance is variable and
has many differential diagnoses. MR imaging is supe-
rior for demonstrating different stages of hemorrhage,
hemosiderin/sclerotic rim, and in displaying the soft
tissues and intramedullary spaces. Accurate knowl-
edge of the extent and character of pseudotumors
gained through sonography, CT, and especially MR
imaging is extremely valuable for optimal manage-
ment. 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 differ-
entiating 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 inher-
itance, can present with varied musculoskeletal man-
ifestation. A proper knowledge of the imaging appear-
ances 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, radiosynar-
throses, and/or prophylactic factor therapy.
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