+++
ESSENTIALS OF DIAGNOSIS
++
+++
GENERAL CONSIDERATIONS
++
The sideroblastic anemias are a heterogeneous group of disorders in which hemoglobin synthesis is decreased because of reduced ability to synthesize heme due to an impaired ability to incorporate iron into protoporphyrin IX. Iron accumulates, particularly in the mitochondria. The disorder is generally acquired; it is most often a subtype of a MDS. Other causes include chronic alcoholism, lead poisoning, copper deficiency, medications (isoniazid and chloramphenicol), and chronic infection or inflammation. Inherited forms are usually X-linked, but rare recessive forms have been documented. Modern classification divides sideroblastic anemia into two categories: dyserythropoiesis (ie, hypohepcidinemia) or transfusion-dependence (MDS, thalassemia, etc.).
++
Patients have no specific clinical features other than those related to anemia. The anemia is usually moderate, with hematocrits of 20–30%, but transfusions may occasionally be required. In the sideroblastic subtype of MDS, the MCV is usually normal or slightly increased, as it when due to alcohol. In other types, the MCV is usually low (especially in the inherited forms) leading to confusion with iron deficiency. However, the serum iron level is elevated and the transferrin saturation is high. The peripheral blood smear characteristically shows a dimorphic population of RBCs, one normal and one microcytic. In cases of lead poisoning, coarse basophilic stippling of the RBCs is seen and the serum lead levels will be elevated.
++
The diagnosis is made by examination of the bone marrow. Characteristically, there is marked erythroid hyperplasia, a sign of ineffective erythropoiesis (expansion of the erythroid compartment of the bone marrow without the release of adequate mature RBCs into the peripheral blood) (eFigure 13–6). The Prussian blue iron stain of the bone marrow shows a generalized increase in iron stores and the presence of ringed sideroblasts (erythroid cells with iron deposits in mitochondria encircling the nucleus). Occasionally, the anemia is severe enough to require RBC transfusions. These patients usually do not respond well to recombinant erythropoietin therapy, especially when transfusion requirements are significant. There are occasional responses to oral pyridoxine (50–200 mg/day). Removal of offending toxins and drugs is needed in the secondary acquired forms. A new agent, luspatercept, has been FDA approved for MDS with ringed sideroblasts. It is a TGF-beta ligand trap that promotes erythroid maturation and reduces transfusion needs.
++++
A rare form of sideroblastic anemia is now recognized that is due ...