Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + INTRODUCTION Download Section PDF Listen +++ ++ 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 Graphic Jump LocationTABLE 11–1CLASSIFICATION OF SIDEROBLASTIC ANEMIASView Table||Download (.pdf) 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.) Graphic Jump LocationView Full Size||Download Slide (.ppt) + ACQUIRED SIDEROBLASTIC ANEMIA Download Section PDF Listen +++ +++ Primary ++ There is a clonal (neoplastic) anemia with varying frequencies of neutropenia and thrombocytopenia or less commonly thrombocytosis. This feature of the myelodysplastic syndromes is discussed in Chap. 44. +++ Secondary ++ The anemia is most commonly associated with use of isonicotinic acid hydrazide, pyrazinamide, or cycloserine. It is common in the marrow of alcoholics and a diagnostic feature of the anemia of alcohol abuse. — In the anemia of chronic alcoholism, folate deficiency may coexist as a result of inadequate diet. Thus, the anemia may have megaloblastic features and ringed sideroblasts. On removal of alcohol and replacement of folate, the megaloblastic features disappear first, and the sideroblastic features disappear at a later time as long as abstinence from alcohol is in place. Anemia may occur in patients with neoplastic or chronic inflammatory diseases. Anemia may be severe and is characterized by dimorphic red cells on the blood film, hypochromic and normochromic. If drugs are responsible, the anemia responds promptly to withdrawal of the offending agent. In cases related to an underlying disease, improvement is associated with successful treatment of the primary disease. + HEREDITARY SIDEROBLASTIC ANEMIA Download Section PDF Listen +++ +++ Inheritance ++ The X-linked form is a result of mutations of erythroid-specific ALA synthase (ALAS2). Some autosomal forms have also been described. A mitochondrial deletion causes Pearson marrow-pancreas syndrome. — This condition is generally not inherited but arises from de novo mutations that likely occur in early embryonic development. +++ Clinical and Laboratory Manifestations ++ Anemia appears in the first few weeks or months of life. It is characteristically microcytic and hypochromic. There is prominent red cell dimorphism, with striking anisocytosis and poikilocytosis. Splenomegaly is usually present. Iron overload develops frequently. +++ Treatment ++ Patients with hereditary sideroblastic anemia may respond to pyridoxine in oral doses of 50 to 200 mg daily. Folic acid administered concomitantly may increase the response. Full normalization of the hemoglobin level is usually not achieved, and relapse occurs if pyridoxine therapy is stopped. Efforts should be made to reduce iron overloading by phlebotomy, if possible when anemia is mild or by iron chelators, if phlebotomy is not tolerated (see Chap. 9). ++ For a more detailed discussion, see Prem Ponka and Josef T. Prchal: Hereditary and Acquired Sideroblastic Anemias, Chap. 5 in Williams Hematology, 9th ed.