Hereditary and Acquired Sideroblastic Anemias | Williams Manual of Hematology, 9e | AccessHemOnc

INTRODUCTION

Sideroblastic anemias may be acquired or hereditary and are classified in Table 11–1.
Normal red cell precursors have cytoplasmic organelles termed siderosomes that contain aggregated iron-rich ferritin. They can be seen in erythroblasts by transmission electron microscopy and represent normal structures providing iron for hemoglobin synthesis. These aggregates may be below the resolution of the light microscope. Thus, in Prussian blue–stained marrow specimens, about 20% to 40% of red cell precursors have one to three very small, pinhead-sized blue granules in the cytoplasm under oil immersion optics, depending on the quality of the preparation.
Pathologic sideroblasts are of two types. The classical type is a ringed sideroblast with large, Prussian blue–stained granules in a circumferential position around the nucleus of the erythroblast. This position reflects their intramitochondrial location: mitochondria in erythroblasts being positioned closely surrounding the nucleus. The other type of pathologic sideroblast has large and multiple cytoplasmic granules (see Figure 11–1).
Sideroblastic anemias are characterized by:

— Commonly a population of hypochromic erythrocytes in the blood film (dimorphic picture)

— Increased red cell precursors in the marrow in the face of anemia and a low reticulocyte count

— Anemia that is the result of apoptosis of late erythroid precursors (ie, ineffective erythropoiesis), with increased plasma iron turnover and normal to decreased red cell survival

— Drugs that reduce the formation of pyridoxal 5′-phosphate from pyridoxine decrease heme synthesis and can cause sideroblastic anemia

TABLE 11–1CLASSIFICATION OF SIDEROBLASTIC ANEMIAS

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TABLE 11–1 CLASSIFICATION OF SIDEROBLASTIC ANEMIAS

I. Acquired

A. Primary sideroblastic anemia (myelodysplastic syndromes) (see Chap. 44).

B. Sideroblastic anemia secondary to:

1. Isoniazid

2. Pyrazinamide

3. Cycloserine

4. Chloramphenicol

5. Ethanol

6. Lead

7. Chronic neoplastic disease

8. Zinc-induced copper deficiency

9. copper deficiency from malabsorption.

II. Hereditary

A. X chromosome–linked

1. ALAS2 deficiency

2. Hereditary sideroblastic anemia with ataxia: ABCB7 mutations

B. Autosomal

1. Defects in the erythroid specific mitochondrial carrier family protein SLC25A38

2. Mitochondrial myopathy and sideroblastic anemia (PSU1 mutations)

C. Mitochondrial: Pearson marrow-pancreas syndrome

Source: Williams Hematology, 9th ed, Chap. 59, Table 59–1.

FIGURE 11–1

Marrow films. A. Normal marrow stained with Prussian blue. Note several erythroblasts without apparent siderotic (blue-stained) granules. The arrow indicates erythroblast with several very small cytoplasmic blue-stained granules. It is very difficult to see siderosomes in most erythroblasts in normal marrow because they are often below the resolution of the light microscope. B. Sideroblastic anemia. Note the florid increase in Prussian blue staining granules in the erythroblasts, most with circumnuclear locations. These are classic examples of ringed sideroblast that are by definition pathologic changes in the red cell precursors. In some cases, cytoplasmic iron granules are also increased in size and number, also a pathologic change. (Reproduced with permission from Lichtman’s Atlas of Hematology, www.accessmedicine.com.)