Anemia, Sideroblastic

KEY FEATURES

• Presence of ringed sideroblasts in the bone marrow

• Elevated serum iron levels and transferrin saturation

• Heterogeneous group of disorders in which reduced hemoglobin synthesis occurs because of

  • Reduced ability to synthesize heme due to

  • An impaired ability to incorporate iron into protoporphyrin IX

• Iron accumulates, particularly in mitochondria

• Modern classification divides sideroblastic anemia into two categories

  • Dyserythropoiesis (ie, hypohepcidinemia)

  • Transfusion-dependent, eg

    • Myelodysplastic neoplasms

    • Thalassemia

• Most often it is a subtype of myelodysplastic neoplasms

• Other causes include

  • Chronic alcohol use disorder

  • Lead poisoning

    Copper deficiency (hypocupremia)

  • Medications

    • Isoniazid

    • Chloramphenicol

  • Chronic infection or inflammation

• Inherited forms are usually X-linked but rare recessive forms have been documented

CLINICAL FINDINGS

• Symptoms of anemia; no other specific clinical features

• In hypocupremia (copper deficiency), myelopathy or demyelinating peripheral neuropathy in some patients

DIAGNOSIS

• Anemia usually moderate, hematocrit 20–30%

• Mean corpuscular volume (MCV)

  • Usually normal or slightly increased in sideroblastic subtype of myelodysplastic neoplasms

  • Usually low in other subtypes

    • Especially inherited forms

    • Leading to confusion with iron deficiency

• Peripheral blood smear characteristically shows

  • Dimorphic population of red blood cells

  • One normal and one hypochromic

• In cases of lead poisoning

  • Coarse basophilic stippling of red blood cells

  • Elevated serum lead level

• Bone marrow iron stain shows

  • Generalized increase in iron stores

  • Ringed sideroblasts

    • Red blood cells with iron deposits in mitochondria

    • Encircling the nucleus

  • Marked erythroid hyperplasia resulting from ineffective erythropoiesis

    • Expansion of erythroid compartment of bone marrow

    • Without release of adequate mature red blood cells into peripheral blood

• Serum iron level and transferrin saturation are high

• In hypocupremia

  • Normocytic anemia in two-thirds of cases; macrocytic in remainder

  • Zinc level is often elevated due to

    • Zinc-imbedded dental fillings

    • Excessive oral zinc intake

    • Gastric bypass surgery

  • Neutropenia or thrombocytopenia may be present

  • Bone marrow biopsy

    • Usually interpreted as "myelodysplastic syndrome" due to the presence of ringed sideroblasts and vacuolization of the myeloid and erythroid progenitors

TREATMENT

• Occasionally, red blood cell transfusion is required for severe anemia

• Recombinant erythropoietin therapy is not usually effective

• Oral pyridoxine (50–200 mg/day) occasionally useful

• Removal of offending toxins and drugs is needed in the secondary acquired forms

• Luspatercept

  • FDA approved for myelodysplastic neoplasms with ringed sideroblasts

  • It is a TGF-β ligand trap

  • Promotes erythroid maturation

  • Reduces need for transfusion

• Hypocupremia

  • Administer copper sulfate (2.5 mg orally twice daily)

  • Associated with high hematologic response rate but low neurologic response rate

  • Exogenous or endogenous zinc exposure needs to be eliminated

• Refer to hematologist if diagnostic or transfusion support is needed.