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 (see Table 11–1) and are characterized by: — Ringed (pathologic) sideroblasts and increased storage iron in the marrow are the hallmarks of this group of disorders. — Increased red cell precursors in the marrow in the face of anemia and a low reticulocyte count (ineffective erythropoiesis). The anemia is the result of increased apoptosis of late erythroid precursors. — A population of hypochromic erythrocytes in the blood film is a common finding. All normal red cell precursors have siderosomes, iron-containing cytoplasmic aggregates in the cytoplasm, a normal part of intraerythrocytic iron metabolism and hemoglobin synthesis. They can be seen by transmission electron microscopy. These aggregates are often below the resolution of the light microscope. Thus, in Prussian blue-stained marrow specimens, about 20 to 50 percent of normal red cell precursors can be found to 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 relatively large, Prussian blue-stained granules in an approximate circumferential position around the nucleus of the erythroblast. This location 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 Fig. 11–1). Drugs that reduce the formation of pyridoxal 5′-phosphate from pyridoxine decrease heme synthesis and cause sideroblastic anemia. The main factor responsible for the anemia is ineffective erythropoiesis, with increased plasma iron turnover, normal to decreased red cell survival, and increased excretion of fecal stercobilin. ++Table Graphic Jump LocationTABLE 11–1CLASSIFICATION OF SIDEROBLASTIC ANEMIASView Table||Download (.pdf) TABLE 11–1 CLASSIFICATION OF SIDEROBLASTIC ANEMIAS Acquired Primary sideroblastic anemia (myelodysplastic syndromes) (see Chap. 42) Sideroblastic anemia secondary to: Isoniazid Pyrazinamide Cycloserine Chloramphenicol Ethanol Lead Chronic neoplastic and inflammatory disease Zinc Hereditary X chromosome–linked ALAS2 deficiency Hereditary sideroblastic anemia with ataxia: ABCB7 mutations Autosomal: mitochondrial myopathy and sideroblastic anemia (PSU1 mutations) Mitochondrial: Pearson marrow-pancreas syndrome Source: Williams Hematology, 8th ed, Chap. 58, Table 58–1, p. 866. ++ 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, which 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.) (Source: Williams Hematology, 8th ed, Chap. 58, Fig. 58–1, p. 866.) Graphic Jump LocationView Full Size||Download Slide (.ppt) + ACQUIRED SIDEROBLASTIC ANEMIA Download Section PDF Listen +++ +++ Primary ++ A clonal (neoplastic) anemia with varying frequencies of neutropenia and thrombocytopenia or occasionally thrombocytosis. This feature of the myelodysplastic syndromes is discussed in Chap. 42. +++ Secondary ++ Most commonly associated with use of isonicotinic acid hydrazide (INH), pyrazinamide, or cycloserine. Common in the marrow of abusers of alcohol 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 siderblasts. 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. 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. +++ Clinical and Laboratory Manifestations ++ Anemia appears in the first few weeks or months of life. Characteristically microcytic and hypochromic. Prominent red cell dimorphism, with striking anisocytosis and poikilocytosis. Splenomegaly is usually present. Hemochromatosis develops frequently in these patients. +++ 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, or by use of desferrioxamine. ++ For a more detailed discussion, see Prem Ponka and Josef T. Prchal: Hereditary and Acquired Sideroblastic Anemias. Williams Hematology, 8th ed, Chap. 58, p. 865.