The hemoglobinopathies encompass a heterogeneous group of diseases in which there is some abnormality of the hemoglobin molecule, frequently associated with hemolytic anemia. The most prevalent of them is sickle-cell disease (SCD), an autosomal recessive condition that predominates in Afro-descendants. In SCD, there is an abnormal form of hemoglobin with a mutant beta globin chain, named hemoglobin S; it predominates over hemoglobin A, which is the dominant form in healthy individuals. Upon deoxygenation, erythrocytes with hemoglobin S lose their malleability and undergo irreversible deformation (sickling), being removed from circulation by the reticuloendothelial system. Thalassemia is the most frequent hemoglobinopathy in individuals with Mediterranean, Arab, or Asian ancestry, characterized by defective formation of alpha or beta chains of the hemoglobin molecule, being the latter (beta-thalassemia) the most common form. Because of its prevalence, SCD will be used as the prototype to describe the imaging findings of hemoglobinopathies unless otherwise specified.

Chronic anemia related to SCD leads to persistence and hyperplasia of the hematopoietic red marrow (see Chap. 2 – Fig. 8.1), with osteoporosis, widening of the medullary cavities, coarse appearance of bone trabeculae, and thinning of the cortex (Fig. 8.2). Classic radiographic findings in the ­calvaria include widening of the diploic space, thickening of the inner table, thinning of the outer table, and prominent trabeculae (hair-on-end sign) (Fig. 8.3). Spinal involvement is characterized by biconcave “fish” (or “fish mouth”) vertebrae, cortical thinning, and weakening of the medullary bone, all related to osteoporosis, with vertebral wedging/collapse in advanced cases (Figs. 8.4 and 8.5).

Abnormalities of bone development are also common in children with SCD, mostly related to ischemia of the growth cartilages (vasoocclusion due to trapping of the abnormally shaped erythrocytes). In the ankles, ischemic changes typically occur in the lateral portion of the distal tibia, leading to medial inclination of the tibiotalar joint surfaces (tibiotalar slant – Fig. 8.6). Sharply delimited depressions of the vertebral endplates (“H-shaped” vertebra) are related to centrally located infarctions and abnormal endochondral bone formation (Figs. 8.4 and 8.7). Protrusio acetabuli is found in up to 20 % of the patients, secondary to ischemic involvement of the triradiate cartilage.

The so-called hand-foot syndrome (sickle-cell dactylitis) is characterized by recurrent episodes of pain and swelling of hands and feet related to infarction of the diaphyses of the small tubular bones. It is typical of small children (before age 2), consisting in one of the earliest manifestations of SCD. Radiographs are insensitive during the early stages, and characteristic radiographic findings (which include mottled osteoporosis, periosteal reaction, bone neoformation, and cortical thickening) may take some weeks to become apparent (Fig. 8.8). Moth-eaten lesions may be seen in more severe cases, and in long-standing disease, there is squaring and widening of the small tubular bones of hands and feet (Figs. 8.2 and 8.9).

Painful episodes of vasoocclusion leading to acute bone infarction are the most frequent musculoskeletal complication of SCD after the second year of life, affecting mainly the long bones, vertebrae, and ribs. Even though radiographs are often normal in the early stages, lucent areas appear as bone destruction advances (Fig. 8.10). Chronic bone infarcts in the long bones appear as centrally located metadiaphyseal/­diaphyseal lesions that exhibit a serpiginous calcified rim (Figs. 8.11 and 8.12), while marked sclerosis is found in chronic infarcts of the pelvic bones and of the vertebrae (Fig. 8.13). Additional findings that may be related to chronic infarcts include cortical thickening, layered periosteal reaction, and a “bone-within-bone” appearance (Figs. 8.11, 8.12, 8.13, and 8.14). Bone infarcts usually display normal or decreased uptake on bone scintigraphy in the first few days after the ischemic insult, showing increased uptake after the onset of revascularization; necrotic areas will remain “cold,” while ischemic bone with adequate revascularization will return to its normal appearance within a few months. On MRI, acute infarctions are ill-defined and may present a nonspecific edematous appearance; in time, however, hemoglobin degradation products eventually appear (showing high signal intensity on T1-WI and T2-WI), and heterogeneous post-gadolinium enhancement is often present (“ink stain” pattern), with surrounding bone marrow edema (Figs. 8.13, 8.15, and 8.16). On the other hand, chronic bone infarcts are geographic and well defined, presenting a hypointense rim on T1-WI and T2-WI and variable signal intensity in the central portion (Fig. 8.16). Avascular necrosis (epiphyseal infarct) in SCD is more common in adults than in children. The ­epiphyses of the proximal femur and of the proximal humerus are the preferential sites, with imaging findings similar to those of Legg-Calvé-Perthes disease, discussed in Chap. 7; lesions are usually larger and more frequently bilateral in SCD if compared to other causes of avascular necrosis (Figs. 8.13, 8.17, and 8.18). Subperiosteal fluid collections and hematomas are occasionally found in the limbs (Fig. 8.19), although they are more common in the orbits, associated with bone infarcts.