Haemolytic anemias

RADIOLOGY OF HAEMATOLOGICAL

DISORDERS

Numerous blood-related disorders, including various

anemias leukemias lymphomas and clotting-deficient diseases (hemophilia) can

cause skeletal alterations The most notable osseous changes are seen in

the congenital hemolytic anemias (thalassemia , sickle cell anemia.

Chronic iron deficiency anemia produces minor skeletal changes, usually isolated to the skull.

Thalassemia Thalassemia is characterized by abnormal

hemoglobin synthesis that produces variable degree of anemia.

Classified according to the severity of the disease:

Thalassemia major, Thalassemia minor, and Thalassemia intermedia. The effects on the skeleton can be severe and

manifest radiographically as signs of increased marrow hematopoiesis.

Clinical features Most frequently arthralgia (30%) and low back

pain (25%) Cardiac failure due to repeated blood

transfusions. Physical findings include pallor, lethargy,

retarded growth, hepatosplenomegaly , mongoloid facies, maxillary overgrowth (rodent facies), and inhibited sexual development.

Rarely, epidural extramedullary hematopoietic tissue in the spinal cord can produce spinal cord compression.

Laboratory examination : hypochromic microcytic anemia, reticulocytosis, nucleated red blood cells, target cells,

and elevated serum bilirubin

Pathologic Features: The essential defect is an imbalance in globin

chain production (α- and β-chains), which leads to ineffective hemopoiesis, hemolysis, and anemia.

In infants and children the entire skeleton is involved

because of the presence of red marrow. With increasing age there may be regression of

peripheral skeletal changes because the red marrow is normally replaced by fatty marrow.

In contrast, the pelvis, spine, and skull may show progression of changes with age.

General features: Coarsened trabecular

pattern(honeycomb) Cortical thinning Expanded bone

calibre Osteoporosis Vascular channel

enlargement Widened medullary

cavity

Special features: Erlenmeyerflask

deformity Hair on end

appearance of skull Paraspinal

extramedullary haematopoiesis

Growth Disturbances: There is a lack of remodeling within long bones,

resulting in undertubulation, especially at the metadiaphyseal junction.

This produces an Erlenmeyer flask-type deformity.

Premature fusion of a portion of a growth plate may result in Shortening and deformity, particularly in the proximal humerus and distal femur.

Miscellaneous: Fractures, avascular necrosis, chondrocalcinosis, hemochromatosis, arthropathy may be seen.

Skull. In the calvaria, there is a distinct lack of

changes below the inferior occipital protuberance owing to the lack of marrow in this area.

The frontal bones reveal the earliest and most severe changes.

Three patterns of involvement may be visible: granular osteoporosis, widened diploe, and vertical radiating spicules of new bone (hair-

on-end appearance) with loss of definition of the outer table.

Circumscribed lytic lesions of the calvaria up to 5 cm are occasionally seen.

The vascular impressions from the middle meningeal arteries are often enlarged and prominent.

In the facial bones, the effects of erythroid hyperplasia may be severe, a feature rarely seen in sickle cell anemia.

The major abnormalities are lack of pneumatization of the frontal, maxillary, sphenoid, and mastoid air cells but not the ethmoids, which remain aerated.

The orbits may be displaced laterally, and the upper incisors may be displaced forward, producing malocclusion (rodent facies).

Spine: osteopenia, coarse vertical trabeculae, thin

cortical outlines, and involvement of both the body and neural arch of each segment. also seen in the sacrum and pelvis.

Extramedullary hematopoiesis affecting the spinal cord or nerve roots may exit but is rare.

MRI and CT examination are essential to assess these lesions.

On MRI, the mass appears heterogenous on both T1- and T2-weighted images with enhancement on administration of paramagnetic agents.

Chest. Cardiomegaly is a consistent finding. Posterior mediastinal extramedullary hemopoietic

masses will be evident as bilateral opaque paraspinal lobulated masses below the diaphragm.

liver and abdominal lymph nodes may be radiopaque owing to hemosiderin deposits.

The ribs are widened and osteopenic with a coarsened trabecular pattern.

Characteristically, there is a symmetric, bulbous enlargement of the posterior ribs.

Sicklecell anaemia Sickle cell disease is a chronic, congenital, and

hereditary hemolytic anemia. It was first described in 1910 by Herrick. It is characterized pathologically by an abnormal

molecular structure of hemoglobin that, under low oxygen tension, will distort the red blood cell into an

elongated, curved, sickle configuration. The end result is increased hemolysis, vascular

occlusion, and tissue anoxia. The osseous changes are primarily related to

infarction, avascular necrosis, marrow hyperplasia, and retarded growth.

Clinical Features All individuals who possess the sickle cell hemoglobin

(Hb) do not necessarily have symptoms or radiographic changes.

Usually, only those that are homozygous (Hb SS) have symptoms.

The onset of clinical signs and symptoms in homozygous patients is usually after 6 months of age, owing to the progressive decrease in levels of fetal hemoglobin (Hb F).

Weakness and pallor are usual but non-specific. Episodic abdominal crises, jaundice, acute bone pain,

and dactylitis.

A common symptom in infancy is the so-called hand-foot syndrome.

This consists of painful swellings of the hands and feet and is the result of either infarction or Salmonella infection.

predisposition to develop Salmonella osteomyelitis, which at times will be bilateral and symmetric The incidence of femoral and humeral head necrosis is equal, but the incidence of postprosthesis failure is as much as 50%.)

Occasionally, widespread generalized bone marrow necrosis is evident in patients with sickle cell disease.

Initial splenic enlargement, usually up to approximately

10 years of age, later, with progressive infarction and fibrosis, the spleen may completely atrophy, resulting in

autosplenectomy. Cardiomegaly is a common complication. Gallstones may be found in up to 65% of patients,

owing to hyperbilirubinemia from increased hemolysis. Mesenteric vascular thromboses result in acute,

severe abdominal pain, the so-called sickle cell crisis. Renal failure from papillary necrosis also occurs.

SICKLE CELL ANEMIA: ABDOMINAL CRISIS. Observe the numerous dilated loops of small intestinethat are the result of acute mesenteric thrombosis

SPINE: In the developing spine, vascular compromise and

regional ischemia result in a unique vertebral body endplate configuration (fish vertebrae, step-down sign, H vertebra, Reynolds’ phenomenon).

The central portion of the endplate receives a direct blood supply from branches of the nutrient artery.

At the periphery of the endplates there is a diffuse network of anastomotic perforating vessels.

This pattern of vascular distribution and circulatory dynamics results in ischemia of the central endplate zone when the nutrient artery becomes obstructed, such as in a sickling crisis.

The peripheral vessels, allow collateral circulation to develop more easily if they become obstructed.

SICKLE CELL ANEMIA: SPINAL CHANGES. A. Normal. Normal circulatory dynamics in a developing vertebral body. B. After Thrombosis. Following thrombosis of the central nutrient vessels, central growth is inhibited, producing the characteristic H vertebra. C. Early Changes. Note that initially, the depression of the endplates is smooth, concave, and shallow. D. Later Changes. Observe that later the configuration becomes sharpand more characteristic

Skeletal manifestations generalized osteopenia, coarsened trabecular pattern, large vascular channels, widened medullary cavity, cortical thinning, and a loss of the

diaphyseal constriction in the small tubular bones.

Skull: the osseous changes are limited to the area above the internal occipital protuberance because of the absence of marrow below this point.

Skull changes consist of a widened diploic space, granular texture and, in severe cases, a hair-on-end trabecular pattern.

In the adult a generalized sclerotic pattern may appear in the entire skeleton, except in the spine, due to chronic endosteal appositional new bone formation.

Splenic infarcts, appearing as punctate or amorphous calcific configurations, are seen in up to 30% of patients with sickle cell anemia.

Infarction: The earliest radiographic sign, especially in the tubular

bones of the hands and feet, is initial soft tissue swelling, followed in about 2 weeks by diaphyseal and linear periostitis.

Gadolinium-enhanced MRI is unreliable in distinguishing between osteomyelitis and bone infarction.

The best method for differentiation is the combined use of technetium and gallium scintigraphy, by which both show focal uptake in the presence of infection in contrast to infarctions, which show uptake of technetium but normal to low uptake of gallium.

MRI shows acute infarction as reduced signal on T1- and increased signal on T2-weighted studies.

Serpiginous, medullary infarcts are sometimes seen.

Infarction of an epiphysis, especially of the femoral and humeral heads, is identical to the idiopathic or post-traumatic forms of ischemic necrosis in these locations.

Alterations in bone growth result in cupped metaphyses and shortened bone length.

Protrusio acetabuli may be evident in up to 5% of males and 12% of females.

SICKLE CELL ANEMIA: MARROW CONVERSION. A. T1-Weighted MRI, Coronal Knee. B.T2-Weighted MRI, Coronal Knee. Note that the low signal intensity seen in the distal femur abutting the metaphysis is abnormal reconversion of red marrow from yellow marrow. COMMENT: This 27-year-old sickle cell patient was not a smoker. This marrow conversion was associated with the hemolytic abnormality of sickle cell anemia.

Manifestations of marrow hyperplasia: Cortical thinning Large vascular channels Diffuse decrease in bone density Loss of diaphyseal constriction Sparse and coarsened trabecular pattern Widened medullary cavity

Osteomyelitis: Causative organism is Salmonella

paratyphi Bilateral Symmetrical Diaphyseal Prominent, moth-eaten pattern of

destruction and periosteal response. Prominent involucrum Femur, and tibia.

Long Bones: coarsening of the trabecular pattern patchy medullary sclerosis bone within a bone appearance of the

cortex laminated or solid periosteal new bone growth abnormalities epiphyseal ischemic necrosis

HAEMOPHILIA It is the blood coagulation disorders

characterized by a deficiency of specific clotting factors.

1)Classic hemophilia (hemophilia A) 2)Christmas disease (hemophilia B) Both are sex linked, recessive, and

inherited. Female is the carrier Manifests clinically only in the male.

Clinical features: Mild – bleeding tendencies Severe- spontaneous bleeding or

bleeding from minor injuries Initial - bleeding episodes may resolve

completely with no sequelae. Repeated hemarthroses - precipitate

synovial proliferation (pannus) and synovial hemosiderin deposition

Articular adhesions and progressive Fibrosis of the sub synovium, capsule, and

periarticular tissues Marginal erosions and degenerative changes . Subarticular bone osteoporosis, cysts, and epiphyseal overgrowth may be evident. Intraosseous and subperiosteal hemorrhages

result in localized bone resorption, expansion, and periosteal new bone formation.

Major radiographic features: Soft tissue swelling Osteoporosis Osseous lesion Cartilage destruction Joint disorganisation BONES: Growth abnormalities(epiphysis) Osteoporosis Pseudo tumors Sub chondral cysts

JOINT: Dense joint effusions Destructions Erosions

UNCOMMMON: Chondrocalcinosis Ectopic calcification Fracture Ischaemic necrosis Septic arthritis

General characterstics

Soft Tissue Swelling. increased soft tissue density owing to

hemosiderin may be evident. MRI is useful in depicting synovial hypertrophy,

inflammation, fluid accumulation, and loss of articular cartilage.

Osteoporosis. Subchondral Cysts. Beneath the articular cortex, well-demarcated,

localized regions of radiolucency represent either escaped synovial fluid or localized hemorrhages.

Expansile Bone Lesions (Pseudo-Tumors): Hemorrhage within bone may result in expansile,

geographic lesions simulating a neoplasm (hemophilic pseudotumor).

The occurrence of pseudo-tumors is rare, being estimated in only 1-2% of patients.

Variable, ranging from a small, benign-appearing lesion to a large, aggressive

destruction. The bones most commonly involved are, in order of

frequency, the femur, pelvis, tibia, and hand. Pseudo-tumors can also occur in soft tissues, producing a

cyst-like lesion, which on T1-weighted and T2-weighted MRI studies is of low to heterogeneous signal intensity.

Epiphyseal Abnormalities. In the growing skeleton, chronic

hyperemia of the epiphyseal cartilage can produce accelerated growth and maturation of epiphyses.

The epiphyses appear ballooned and enlarged in relation to the adjacent

diaphysis, similar to the appearance of juvenile rheumatoid arthritis.

HEMOPHILIA: PSEUDO-TUMORS. A. Ilium. B. Femur. C. Calcaneus. Observe the tumor-like expansions of the ilium, femur, and calcaneus that are the result of repeated intraosseous hemorrhage. COMMENT: Hemophiliac pseudo-tumors are most common in the ilium but can be found anywhere in the skeleton. The radiographic appearance of an expansile, trabeculated lesion often makes the exclusion of other tumors, such as plasmacytoma, renal, or thyroid metastases and even giant cell tumors, difficult. When located adjacent to a joint,arthritic changes may provide the key differential clue to the diagnosis.

Joint disorganization: Chronic changes, such as complete loss of joint space, considerable articular fragmentation, sclerosis, osteophytes, and bony misalignment, may become apparent in long-standing hemophilia patients.

The similarity to neurotrophic joint disease is striking.

the knee is the most common site of hemophilic arthropathy.

In general, intra-articular hemorrhage distal to the elbow and ankle is rare.

Distal femur:The femoral condyles are often grossly enlarged, severely osteoporotic, and exhibit an irregular, flattened contour of their articular weight-bearing surfaces.

Widening of the intercondylar notch is thought to be related to repeated hemorrhage at the cruciate ligament attachments.

Proximal tibia: The tibial plateau may be flattened, usually with an irregular articular contour.

The epiphysis is enlarged and osteoporotic, with a thin cortex and accentuated vertical trabeculae.

The proximal fibula exhibits similar abnormalities. Patella: The inferior pole is sharply attenuated and

squared, in contrast to the normal tapered apex. Repeated hemarthrosis during growth periods

inhibits the secondary growth center, resulting in this squared configuration.

The same appearance of the patella is visible in juvenile rheumatoid arthritis.

HEMOPHILIA. A. AP Knee. Note that the overgrowth of the medial condyle has altered the joint orientation. Note the irregular flattened articular contour and widened intercondylar notch. B. Lateral Knee.Observe the increase in the periarticular densitycharacterizing hemosiderin deposits from repeated hemarthrosis.

HEMOPHILIA. A. AP Knee. Observe the altered joint orientation that is caused by overgrowth of themedial condyle, irregular articular surfaces, widened intercondylar notch, and osteoporosis. B. Lateral Knee. Notethat the inferior pole of the patella is squared and attenuated (arrow).

HEMOPHILIA: POLYARTICULAR INVOLVEMENT. A and B. Knee. C. Ankle. D. Shoulder. E.Elbow. F. Wrist. Note that the characteristic features of hemophilic arthropathy are visible in multiple joints insevere, long-standing cases. Observe the destruction of the articular surfaces, regional osteopenia, and secondarydegenerative changes (subchondral sclerosis and cyst formation often are congruent with the patient’s age).

HEMOPHILIA. AP Ankle. Note the prominent osteoporosis and alteration of the ankle mortise jointplane (tibio-talar slant deformity).