AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Background

Thalassemic syndromes are genetically determined disorders of hemoglobin synthesis with decreased production of either alpha or beta polypeptide chains of hemoglobin molecules, which results from markedly decreased amounts of globin messenger ribonucleic acid. The imbalance may result from many genetic lesions.

Pathophysiology

Normal adult hemoglobin is a large complex molecule in which an iron-containing pigment (heme) is conjugated to a complex protein (globin). The globin component consists of a tetrad of 574 amino acids in the form of 2 pairs of unlike polypeptide chains designated by Greek letters. Each molecule consists of 2 alpha and 2 nonalpha chains (eg, beta, gamma, delta) that have well-recognized and consistent amino acid sequences. In the normal adult hemoglobin (HbA), which constitutes over 95% of the hemoglobin in normal persons older than 1 year, the globin component consists of 2 alpha and 2 beta chains (alpha2beta2); the remaining hemoglobin comprises HbA2 (alpha2delta2) and fetal hemoglobin (HbF or alpha2gamma2).

The most important thalassemic syndrome is homozygous beta thalassemia, in which the production of beta chains is markedly decreased or absent, and a consequent decrease in synthesis of total hemoglobin occurs. This results in severe hypochromic anemia. Furthermore, excess alpha chains, which synthesize at the normal rate, precipitate as insoluble inclusion bodies within the erythrocytes and their precursors. The presence of such intracellular inclusion bodies leads to increased erythrocyte hemolysis and to severe ineffective hematopoiesis. Approximately 70-85% of marrow normoblasts are destroyed in severely affected patients. These processes result in profound anemia and an associated increase in marrow activity, which is estimated to increase 5- to 30-fold.

Frequency

United States

An estimated 800-1000 patients have homozygous beta thalassemia in the United States. Most of these patients live in the Northeast between Boston and New York. The heterozygous trait occurs in 2.5% of Italian Americans and 7-10% of Greek Americans.

International

In high-risk areas (ie, Greek and Italian islands), 10% of the population may have homozygous beta thalassemia.

Mortality/Morbidity

Thalassemia major, the homozygous state, is a serious condition that usually becomes apparent within the first year of life. In the untreated patient, hemolysis and profound anemia lead to marrow hypertrophy and hyperplasia. The anemia may be so severe that death may occur in the first 5 years, although regular blood transfusions can prolong life. The long-standing erythrocyte breakdown results in chronic overproduction of bilirubin, which predisposes the patient to formation of pigmentary gallstones and to hemosiderosis resulting from the deposition of excess iron in the reticuloendothelial system, particularly the myocardium, liver, and pancreas. Death from the effects of hemosiderosis may occur before age 25 years. However, since there is a spectrum of severity, some patients may be only mildly affected.

Race

The disorder is common, but not exclusively found, in races bordering the eastern Mediterranean Sea or in families originating from these areas (thalassa means "sea" in Greek). Thalassemia has been identified in people who are Greek, Italian, Slavic, Algerian, Moroccan, Egyptian, Syrian, Armenian, Bukharan, Jewish, Persian, German, Indian, Burmese, Thai, Singhalese, Chinese, Filipino, Mexican, and British. The highest concentrations of the disease are found in Greece, including the Greek islands; in parts of Italy, in particular, the lower Po valley; in southern Italy; and in the Italian islands. Sicily, Corsica, and Sardinia (Italian islands) and Cyprus and Crete (Greek islands) are heavily affected in particular; the higher incidence in these islands likely is because of the higher inbreeding that occurs in isolated populations.

Sex

Male-to-female ratio is equal.

Age

Thalassemia is a genetic disorder that usually does not become apparent until patients are older than 6 months. Survival after age 30 years once was uncommon, but the prognosis has improved through the use of a regimen of hypertransfusion in conjunction with chelation therapy.

Anatomy

Changes that occur in the osseous system of patients with thalassemia major are the result of marrow hypertrophy and hyperplasia in response to chronic anemia. Since hematopoietic marrow normally is found in the axial skeleton and in the proximal portions of the appendicular skeleton, osseous changes are most commonly found in these sites. In infants and children, hematopoietic marrow is distributed throughout the axial and appendicular skeleton, and, consequently, osseous changes may be present distally as far as the phalanges. Abnormalities in the appendicular skeleton become less pronounced as normal developmental regression of red marrow occurs; however, in the presence of severe, prolonged anemia, regression does not occur, and appendicular findings may persist.

Clinical Details

The diagnosis is established in infancy by the onset of a severe hypochromic anemia with splenomegaly and markedly elevated levels of HbF. Family studies show both parents as carriers of the beta-thalassemic trait, which is marked by mild, microcytic, hypochromic anemia and high levels of HbA2.

Early signs and symptoms are associated with the anemia, which is characterized by hypochromic, microcytic red cells with variable numbers of nucleated erythrocytes and reticulocytes. Many of the erythrocytes and their precursors reveal evidence of inclusion bodies (Fessas bodies) consisting of denatured alpha-globin. Pallor, icterus, and cardiac enlargement occur frequently. Marrow hypertrophy and extramedullary hematopoiesis may result in hepatosplenomegaly, as well as skull and facial deformities, in particular, prominence of malar eminences and malalignment of teeth, which gives rise to the characteristic "rodent facies."

Pathologic fractures may occur but are less common than suggested from the radiographic appearance of the bones, which may be explained by the sedentary lifestyle forced upon these patients by their disease process. In the untreated and undertransfused patient, growth retardation is noticeable in the second decade; adults usually are short, and the appearance of secondary sexual characteristics is retarded. Terminal events, including congestive heart failure and arrhythmia, hepatic failure or cirrhosis, and diabetes mellitus, are associated with siderosis of the myocardium, liver, or pancreas.

Before 1965, because of concerns about transfusion-induced iron overload, patients with homozygous beta thalassemia were transfused infrequently to maintain a hemoglobin level just compatible with reasonable activity. The hemoglobin level often was allowed to fall as low as 5-6 g/100 mL. Since that time, patients have been treated with a more aggressive transfusion regimen consisting of transfusions of 15 mL/kg of packed red blood cells every 3-5 weeks to maintain the hemoglobin level above 9.5-10 g/100 mL.

Since 1977, long-term chelation therapy has been used to eliminate excess iron. This treatment, which consists of a slow (ie, overnight) subcutaneous injection of 1.5-2 g deferoxamine 5-6 times per week, creates a negative iron balance, which means that deferoxamine-induced iron excretion exceeds iron delivery by transfusion. Administration of high subcutaneous doses of deferoxamine to young children (before iron overload is established) is associated with a significant decrease in mean body length, joint stiffness, and a ricketslike syndrome.

Patients with thalassemia intermedia are an interesting subset of those with thalassemia, constituting 5-10% of patients with thalassemia major. These patients are able to maintain levels of hemoglobin compatible with an active life (6-9 g/dL) without regular transfusions. They have a milder clinical form of the disease and a longer life expectancy; however, in many patients, this appears to be at the expense of extensive marrow hypertrophy and associated skeletal deformities.

Preferred Examination

Plain radiographs usually are all that are required to confirm the diagnosis. The complete skeleton is involved. The most fruitful areas to radiograph are as follows:

• Anteroposterior (AP) of both hands
• Lateral skull
• AP and lateral of thoracolumbar spine
• AP of abdomen for gallstones
• AP of chest for cardiomegaly, congestive heart failure, and extramedullary hematopoiesis

Limitations of Techniques

Conventional radiography usually confirms the diagnosis.

CT may be required to further evaluate faciomaxillary changes and to clearly define expansile lesions of the pelvis resulting from extramedullary hematopoiesis.

Conventional radiography may not show early extramedullary hematopoiesis, which is best seen on MRI.

DIFFERENTIALS

Section 3 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Other Problems to be Considered

Other chronic anemias
Acute leukemia

RADIOGRAPH

Section 4 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Findings

Radiographically, the skeletal response to marrow proliferation consists of expansion of the medulla, thinning of cortical bone, and resorption of cancellous bone, which results in a generalized loss of bone density. Frequently, small areas of lucency resulting from focal proliferation of marrow may be present, often demarcated by coarsened but less numerous trabeculae. In addition, the hypertrophic and hyperplastic marrow may perforate the cortex, proliferate subperiosteally, and stimulate a variety of periosteal responses. Depending on the bone, these factors may result in a variety of radiographic appearances.

Vertebral bodies

In weight-bearing bones, the resorptive process preserves the primary trabeculae at the expense of secondary trabeculae. In the vertebral bodies, this results in a striated appearance resulting from thickened vertical trabeculae that stand out against the paucity of horizontal trabeculae (Image 1). In severely affected patients, biconcavity of the superior and inferior margins of the vertebral bodies or compression fractures may occur.

Skull and facial bones

In severely affected patients, a widening of the diploic space (medulla) with a thinning of the tables (cortices) occurs, frequently with complete obliteration of the outer table. New bone forms in response to marrow proliferation beneath the periosteum. These bony spicules may be seen radiographically and result in a classic "hair-on-end" appearance. Because it lacks hematopoietic marrow, the occipital bone usually is not involved (Image 2).

Proliferation of marrow within the frontal and facial bones impedes pneumatization of the paranasal sinuses. This results in hypertrophy of osseous structures and a consequent prominence of the lateral margins of the malar eminences, together with anterior and medial displacement of developing teeth. These features explain the clinical findings noted by Cooley. Characteristically, ethmoidal sinuses are not involved, a factor attributable to the absence of red marrow in the sinus walls.

Appendicular skeleton

In patients with more profound anemia, changes may be noted in the distal bones of the extremities. In the most severely affected patients, the phalanges reveal the above-noted changes of cortical thinning, osteopenia, and coarsening of the trabeculae and may lose their normal tubulation, which frequently results in a squared or sausage-shaped configuration (Image 3). Fractures may occur, although less commonly than expected from the degree of osteoporosis (Image 4). The sedentary life these children are forced to live possibly may protect them from frequent injury. In severely affected patients, well-defined erosions of the periosteal margin of the cortex of the metaphysis or diaphysis may be identified.

Ribs

Similarly to the long bones, the ribs may reveal a spectrum of radiographic findings that demonstrate the varied response of the medulla, cortex, and periosteum to proliferating marrow. Evidence of widening, generalized osteopenia or localized lucency resulting from hypertrophy and hyperplasia of marrow within the medulla may be seen. Cortical erosions may be pronounced and are considered to result from focal subperiosteal proliferation of marrow (Image 5).

A frequent finding has been referred to as the "rib-within-a-rib" appearance and is noted particularly in the middle and anterior portions of the ribs. The finding consists of a long linear density within or overlapping the medullary space of the rib and running parallel to its long axis (Image 6). This appearance is not noted in any other portion of the skeleton.

Another finding, which appears limited to the ribs, is the subcortical lucency, consisting of a sharply defined lucency at the margin of the cortex and medulla. This appears to result from erosion of the inner aspect of the cortex and adjacent medullary trabeculae by the leading edge of proliferating marrow. A highly characteristic appearance consists of bulbous expansion of the posterior, and to a lesser extent, anterior segments of the ribs, and frequently is associated with posterior or anterior soft tissue densities, which histologically represent hematopoietic marrow.

Extramedullary hematopoiesis

In the most severely affected patients, and in particular, in patients with thalassemia intermedia, prominent lobulated soft tissue densities may be noted in the posterior mediastinum and, to a lesser degree, in the anterior mediastinum or pelvis. These opacities result from extramedullary hematopoiesis (Image 7). CT, which can evaluate the skeletal system in the axial plane, demonstrates that this proliferating marrow originates within the medulla of adjacent vertebral bodies, ribs, or pelvis.

Although extramedullary, it remains subperiosteal in location and, histologically, shows new bone formation. The presence of extramedullary hematopoiesis within the spinal canal may be associated with the development of spinal cord compression. Rarely, new bone formation within these proliferative subperiosteal masses may be extensive enough to result in osteomatous lesions of the ribs that are apparent radiographically (Image 8). Less frequently, similar osteomata may arise from the long bones.

Vascular impressions

Hematopoietic marrow is vascular and in thalassemia, a 5- to 30-fold increase in activity may occur as a result of marrow hyperplasia and hypertrophy. Not surprisingly, this marrow proliferation is associated with increased blood supply, which may be seen radiographically as an enlargement of the nutrient foramina of the tubular bones, particularly the phalanges (Image 3).

A similar enlargement is noted in other processes associated with increased blood supply to the medullary, including sickle cell disease variants, Gaucher disease, and infectious diseases (including leprosy), as well as noninfectious inflammatory conditions such as hemophilia. The calvarial widening, which occurs in association with marrow hypertrophy, may be associated with markedly enlarged and tortuous vascular impressions of the calvarium (Image 2). Rupture of associated enlarged venous structures may constitute a potential sequela of moderate cranial trauma.

Premature fusion of the epiphyses

Premature fusion of the epiphyses is a characteristic finding in thalassemia. This finding first was described by Currarino and Erlandson, who noted the abnormality in 14% of 79 patients with homozygous beta thalassemia. However, all of the patients were older than 10 years, resulting in an incidence of 23% in patients older than 10 years.

The finding may be unilateral or bilateral and is noted most commonly in the proximal humerus. Less frequently, it may be identified in the distal femur, proximal tibia, and proximal femur. The fusion is associated with a variable degree of shortening and is frequently eccentric, leading to angulation of the prematurely fused epiphyses. In the proximal humerus, this is associated with a humeral varus deformity (Image 9).

Currarino and Erlandson noted that a disproportionate number of patients (36%) had premature closure in the thalassemia intermedia subset of homozygous beta thalassemia. An explanation for premature fusion has been suggested based on the relationship of the cortex and periosteum to the marrow proliferation (most marked in thalassemia intermedia), the fenestration of the metaphyseal cortex, the anatomy of the proximal humerus, and the forces normally exerted across the shoulder joint.

Accumulation of hemolysis products

The increased erythrocyte hemolysis that occurs in thalassemia results in accumulated breakdown products of the heme component of the hemoglobin molecule, bilirubin and iron in particular.

Cholelithiasis

Although cholelithiasis is uncommon in childhood, a well-documented association exists with hemolytic diseases, and these disorders always must be excluded when gallstones are discovered in a child or adolescent. Using oral cholecystography, surgery, or autopsy, an evaluation of gallstone incidence in thalassemia revealed that in 51 patients, aged 10-27 years, choleliths were identified in approximately 24%, a percentage similar to sickle cell disease but lower than the incidence of cholelithiasis in hereditary spherocytosis (46-56%). Ultrasound (US) evaluation would have demonstrated a higher percentage of stones in these disorders.

Hemosiderosis

As a consequence of hemolysis and transfusion, deposition of iron in the form of hemosiderin (an iron-protein complex) may occur in the myocardium, liver, and pancreas, as well as less commonly in the adrenals, thyroid, parathyroid, pituitary, and proximal small bowel. This may result in hemochromatosis and subsequent failure of these organs.

CT may confirm the clinical diagnosis of hemochromatosis by demonstrating iron deposition, particularly in the liver; however, correlations with transfusion history, serum ferritin levels, and organ damage are unsatisfactory.

MRI demonstrates deposits of hemosiderin, which is paramagnetic, in tissues and organs; however, MRI also fails to provide accurate monitoring of iron deposition in these thalassemic patients. An arthropathy resembling primary hemochromatosis has been reported. Arthritis also has been described with the beta thalassemia trait alone (thalassemia minor).

Response to therapy

The modern radiologist is unlikely to encounter the above radiographic thalassemic features other than in teaching files, on visits to Mediterranean countries, or in isolated patients never managed with hyper-transfusion therapy. This is because therapy by hyper-transfusion and chelation has improved both the general health and the radiographic appearance of patients. As a radiologist, obtain a transfusional history for all patients under evaluation and be sure to understand the response of the skeletal system to therapy.

In a review of the ribs of 32 patients with homozygous beta thalassemia, the radiographic appearance of the ribs correlated with transfusional history. In this study, an overwhelming number of children hyper-transfused from an early age showed normal ribs. This was in contrast to patients who were not hyper-transfused until later in childhood or who were never hyper-transfused, who demonstrated a spectrum of radiographic rib abnormalities, the severity of which increased with the delay in initiating transfusional therapy.

The most striking rib changes were present in patients with thalassemia intermedia who were never transfused. Regression of rib abnormalities after transfusion was not uncommon; however, in approximately two thirds of patients, regression did not occur until after the introduction of hyper-transfusion therapy. The changes noted in the ribs appeared to reflect similar changes occurring in the appendicular skeleton.

Similarly, the size of the nutrient foramina in the phalanges and the vascular impressions in the calvarium are related to the age of onset and type of transfusional therapy. However, unlike the skeletal response to marrow proliferation, the enlarged vascular channels do not appear to regress with therapy but remain as a permanent record of earlier marrow changes.

Although US may show gallstones in approximately 42% of sickle cell disease patients aged 15-18 years, the application of the same technique to a group of thalassemia patients maintained on hyper-transfusion therapy revealed gallstones in only 3.6% of patients in a similar age group. This reduction results from the more intensive transfusional regimen, which reduces activity of the patient's bone marrow, diminishes formation of the fragile erythrocytes, and consequently, limits production of excess bilirubin.

Variants

In addition to the homozygous state, the thalassemic gene also may be present in the heterozygous state or in combination with some other abnormal hemoglobin (ie, HbC, HbE, HbH, HbS, HbLepore). With the exception of sickle cell thalassemia, in which radiographic changes may reflect vaso-occlusive phenomena, as well as the changes of marrow hypertrophy, the radiographic appearances of these variants are solely the result of marrow proliferation and, consequently, are dependent on the degree and duration of any anemia and the type of transfusion therapy.

The anemia that occurs in thalassemia minor, HbC thalassemia, and HbH thalassemia usually is mild; consequently, the radiographic changes typically are minimal or normal in these disorders. However, the anemia of HbE thalassemia and HbLepore thalassemia may be pronounced, with subsequent radiographic changes indistinguishable from those of homozygous beta thalassemia.

Degree of Confidence

The radiographic features of thalassemia result from either a generalized marrow hypertrophy and hyperplasia, which may occur in other hemoglobinopathies, or a reticuloendothelial storage process, including Gaucher disease. These may be diagnosed radiologically with a high degree of confidence, although additional clinical and laboratory information may be required for the differential diagnosis of the hemoglobinopathies.

CT SCAN

Section 5 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Findings

CT rarely is of value, yet it may define the anatomy of change in complex bones and confirm the diagnosis of extramedullary hematopoiesis. Although CT confirms the deposition of iron in the liver and other organs, correlation with organ damage, serum ferritin levels, and transfusional history is unsatisfactory.

MRI

Section 6 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Findings

Like CT, MRI rarely is of value, yet it may confirm the diagnosis of extramedullary hematopoiesis. Similarly, MRI confirms the deposition of iron in the liver and other organs, but correlation with organ damage, serum ferritin levels, and transfusional history is unsatisfactory.

ULTRASOUND

Section 7 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Findings

Cholelithiasis is common in untreated thalassemia. US is the modality of choice when gallstones are suggested.

INTERVENTION

Section 8 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Medical/Legal Pitfalls

• No medical/legal pitfalls

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

Media file 1:  Thalassemia. Anteroposterior radiograph of the lumbar spine. Osteopenia is present; note striated appearance of the vertebral bodies resulting from preservation and thickening of the vertical trabeculae. Clips from a previous cholecystectomy are present.
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Media type:  X-RAY

Media file 2:  Thalassemia. Lateral skull radiograph. Widening of the calvarium is present; the outer table overlying the frontal region is obliterated and new bone formation can be seen in the diploë, producing a "hair-on-end" appearance. Note that the occipital bone is uninvolved. The impressions of the calvarial vessels are enlarged.
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Media type:  X-RAY

Media file 3:  Thalassemia. Anteroposterior of the hands. A generalized loss of bone density is observed. The cortex is thinned, and the trabeculae are coarsened and outline localized lucency. Widening of the medullary cavity has resulted in squaring of the metacarpals. Note the enlarged nutrient foramina in the middle phalanges.
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Media type:  X-RAY

Media file 4:  Thalassemia. Anteroposterior radiograph of the forearm. A fracture is noted in the distal radius. Evidence of medullary expansion and cortical thinning is observed.
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Media type:  X-RAY

Media file 5:  Thalassemia. Radiograph of the ribs. Erosions of the inferior cortical margins of the third, fourth, and fifth ribs are noted.
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Media type:  X-RAY

Media file 6:  Thalassemia. Radiograph of the ribs. Note the long linear density within the medulla, which runs parallel to the long axis of the rib and is most pronounced in the mid and anterior portions of the ribs.
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Media type:  X-RAY

Media file 7:  Thalassemia. Extramedullary hematopoiesis. Lobulated soft tissue opacities are noted overlying the ribs anteriorly and posteriorly.
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Media type:  X-RAY

Media file 8:  Thalassemia. Radiograph of the ribs. An osteoma is seen arising from the third rib anteriorly. The ribs are widened, are osteopenic, and demonstrate multiple areas of focal lucency.
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Media type:  X-RAY

Media file 9:  Radiograph of right and left shoulders. Fusion of the left proximal physis medially associated with a humeral varus deformity is seen. The right physis is normal.
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Media type:  X-RAY

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• MRI
• Ultrasound
• Intervention
• Multimedia
• References

• Borgna-Pignatti C, De Stefano P, Pajno D. Cholelithiasis in children with thalassemia major: an ultrasonographic study. J Pediatr. Aug 1981;99(2):243-4. [Medline].
• Caffey J. Cooley's anemia: a review of the roentgenographic findings in the skeleton. AJR Am J Roentgenol. 1957;78:381.
• Cooley TB, Witwer ER, Lee P. Anemia in children with splenomegaly and peculiar changes in the bones. Am J Dis Child. 1927;34:347.
• Currarino G, Erlandson ME. Premature fusion of the epiphyses in Cooley's anemia. Radiology. 1964;83:656.
• Dewey KW, Grossman H, Canale VC. Cholelithiasis in thalassemia major. Radiology. Aug 1970;96(2):385-8. [Medline].
• Korsten J, Grossman H, Winchester PH. Extramedullary hematopoiesis in patients with thalassemia anemia. Radiology. May 1970;95(2):257-63. [Medline].
• Lawson JP, Ablow RC, Pearson HA. Calvarial and phalangeal vascular impressions in thalassemia. AJR Am J Roentgenol. Sep 1984;143(3):641-5. [Medline].
• Lawson JP, Ablow RC, Pearson HA. Premature fusion of the proximal humeral epiphyses in thalassemia. AJR Am J Roentgenol. Feb 1983;140(2):239-44. [Medline].
• Lawson JP, Ablow RC, Pearson HA. The ribs in thalassemia. I. The relationship to therapy. Radiology. Sep 1981;140(3):663-72. [Medline].
• Lawson JP, Ablow RC, Pearson HA. The ribs in thalassemia. II. The pathogenesis of the changes. Radiology. Sep 1981;140(3):673-9. [Medline].
• Long JA Jr, Doppman JL, Nienhuis AW. Computed tomographic studies of thoracic extramedullary hematopoiesis. J Comput Assist Tomogr. Feb 1980;4(1):67-70. [Medline].
• Long JA Jr, Doppman JL, Nienhus AW. Computed tomographic analysis of beta-thalassemic syndromes with hemochromatosis: pathologic findings with clinical and laboratory correlations. J Comput Assist Tomogr. Apr 1980;4(2):159-65. [Medline].
• MGH. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 3-1968. N Engl J Med. Apr 4 1968;278(14):782-91. [Medline].
• Moseley JE. Bone Changes in Hematologic Disorders (Roentgen Aspects). New York: Grune & Stratton;1963:26.

Article Last Updated: Oct 27, 2004