Chapter 11: Hereditary and Acquired Sideroblastic Anemias

INTRODUCTION

• 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.