Type 3: Acquired Reversible Sideroblastic Anemia(ARSA)

A secondary form of anemia, where the cause is resultant of another problem.

Drugs/medications are the more common causes of this anemia:

• Isoniazid, an anti-tubercular drug, inhibits reactions requiring pyridoxal-5'-phosphate as a coenzyme.
• Chloramphenicol: anti-bacterial, blocks mitochondrial protein and heme synthesis.
• Cytotoxic drugs and poisons probably work similar to isoniazid and chloramphenicol.
• Copper deficiency has been reported to contribute to the development of this anemia.

Infections and leukemias in context with the medications used as therapeutic measures.

If the causative agent is removed, then the anemia is reversed.

Ethanol ingestion (alcoholism): Blocks heme synthesis.This form of anemia is seen in 30% of alcoholics admitted to the hospital. Lead poisoning induces several effects, one of which is sideroblastic anemia.

• Lead consumption, regardless of the route, interferes with iron storage in the mitochondria inducing classical S.A.
• Lead also damages a minimum of six enzyme required for the synthesis of hemoglobin. The life span of the RBC is shortened. The enzyme “δ-aminolevulinic dehydrase” is most sensitive to lead of all the enzymes. δ-aminolevulinic acid is elevated in lead poisoning, making it a good indicator for lead toxicity.

Clinical laboratory findings that indicate lead poisoning are:

• Basophilic stippling
• Reticulocytosis
• Leukocytosis with increased eosinophils
• Presence of reactive lymphocytes
• Increased Hemoglobin F

Iron studies of sideroblastic anemia tend to demonstrate the following:

• High plasma and tissue iron content.
• Free erythrocyte protoporphyrin is increased. This is due a defect in incorporating Fe++ into the protoporphyrin IX molecule to form heme.
• The TIBC will be low or normal. The high plasma iron concentration keeps the iron bearing proteins saturated.
• Serum ferritin is increased.
• Percent iron saturation of ferritin is increased.

When examining the bone marrow of a sideroblastic anemic patient you may see:Presence of erythroid hyperplasia. Megaloblastosis MAY BE present. The degree of megaloblastosis is dependent upon the severity of the anemia. Megaloblastosis is usually associated with a deficiency in vitamin B12 and/or folic acid.

• If megaloblastosis is present, then the giant erythrocyte precursors will give rise to the following maturation sequence:megaloblastic rubriblast, megaloblastic prorubricyte,megaloblastic rubricyte,megaloblastic metarubricyte,macrocytic
• polychromatophilic cell,macrocyte.
• Aggregates of iron granules may be observed in the cytoplasm.
• The normal RBC series (rubriblast, prorubricyte, rubricyte, metarubricyte) may present a cytoplasm that appears to be poorly hemoglobinized. The cytoplasm may also appear scanty and frayed.
• Macrophages may be observed and may contain increased amounts of storage iron.
• Presence of sideroblasts. This is the distinguishing feature of this type of anemia. A normal rubriblast may contain up to five small granules of iron. If more than six granules of iron are observed then this may be considered a pathological condition. The iron granules can be demonstrated using Perls’ Prussian blue iron stain.

Early normal immature erythrocytes (this range as been cited from a low 20% to a high of 80%) will contain an occasional free siderotic granule located in the cytoplasm, but not in any organelle. Some textbooks set the range from 30 to 50%, which may be more realistic.

In sideroblastic anemia, look for 10% to 40% of the RBC precursors to contain increased siderotic granules around the nucleus. If the siderotic cells are predominately early RBC precursors, then this is probably a hereditary form of sideroblastic anemia. If the affected cells include the late precursor cells, then this would be an indicator of an acquired form of sideroblastic anemia. Note that target cells are usually not observed in stained blood films.