Sideroblastic Anemias Workup: Approach Considerations, Complete Blood Cell Count and Peripheral Smear, Iron and Other Laboratory Studies

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Workup

Approach Considerations

The workup for sideroblastic anemia may include the following:

Complete blood count (CBC)
Peripheral smear,
Iron studies (eg, ferritin and total iron-binding capacity [TIBC])
Bone marrow aspiration and biopsy
Other studies as appropriate

Complete Blood Cell Count and Peripheral Smear

In patients with sideroblastic anemia, the CBC usually reveals anemia, mostly moderate, although severe anemia has been reported.^[61]The mean corpuscular volume (MCV) is usually low, with a microcytic picture; however, normocytic, macrocytic,^[62]and classic dimorphic (normocytic + microcytic)^[63]smears are not uncommon.

Siderocytes with Pappenheimer bodies (hypochromic erythrocytes with basophilic iron deposits) are sideroblasts that have matured enough to make it to peripheral blood.

Dimorphic anemia is not specific for sideroblastic anemia and is also seen in combined vitamin B-12 deficiency with iron deficiency and after blood transfusions.^[64]Other cell lines may be undisturbed in pure sideroblastic anemia, but in sideroblastic anemia that is associated with myelodysplastic syndrome (MDS), leukopenia, thrombocytopenia, or even thrombocytosis may be observed.

The peripheral smear may exhibit basophilic stippling in cases of lead poisoning.^[65]

Iron and Other Laboratory Studies

Iron studies may show increased an iron level with decreased TIBC (see the image below) . A very low ferritin level strongly favors iron deficiency as the primary cause of anemia. In fact, iron deficiency may mask underlying sideroblastic anemia as hypochromic anemia, with the appearance of sideroblasts in bone marrow once the iron stores are replenished.^[66]Periodic iron studies are essential even for those who are not transfusion dependent.

Iron and total iron-binding capacity in physiology and pathology.

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Serum lead, alcohol, γ-glutamyltransferase (GGT), copper, and zinc levels can be measured. Surrogates for vitamin B-6 that can be measured in plasma include pyridoxal 5′ phosphate (PLP) and 4-pyridoxic acid (4-PA).^[67]4-PA can also be measured in urine.

Additional Tests

Magnetic resonance imaging (MRI) of the posterior cranial fossa is indicated in anemia-ataxia syndromes to rule out primary cerebellar pathology such as space-occupying lesions.

In congenital or suspected congenital anemias, determination of the exact mutation type (eg, ABC7) may provide useful information for the physician and the family members of affected patients, even if it may not affect immediate patient management. This can be accomplished by means of polymerase chain reaction (PCR) evaluation.

A urine porphyrin profile may reveal erythropoietic porphyria.

Bone Marrow Aspiration and Biopsy

Usually, when a physician is faced with the diagnosis of sideroblastic anemia, bone marrow aspiration and biopsy has already been done. Attention should be paid to other cell lines (ie, megakaryocytes, myelocytes) because MDS is a part of the differential diagnosis (see Differentials). If iron deficiency anemia is of unclear etiology and fails to respond to iron replacement during the workup, bone marrow aspiration and biopsy should be included in the workup.

Patients initially presenting with hypochromic anemia may end up receiving iron supplements if a bone-marrow biopsy is not performed and thus develop iron overload.

It is important to obtain cytogenetic studies on the bone marrow aspirate samples, as quite often this may be the only way confirm a myelodysplastic syndrome.

Histologic Findings

In the revised WHO classification, if an SF3B1 mutation is identified, a diagnosis of MDS-RS may be made if ring sideroblasts comprise as few as 5% of nucleated erythroid cells, whereas at least 15% ring sideroblasts are required in cases lacking a demonstrable SF3B1 mutation.^[3]

The WHO criteria for MDS/MPN-RS-T include thrombocytosis (≥450 × 10⁹/L) associated with refractory anemia, dyserythropoiesis in the bone marrow with ring sideroblasts accounting for 15% or more of erythroid precursors, and megakaryocytes with features resembling those in primary myelofibrosis (PMF) or essential thrombocythemia (ET).Unlike MDS-RS the number of ring sideroblasts required for a diagnosis of MDS/MPN-RS-T is not altered by the presence or absence of a mutation in SF3B1.^[3]

Treatment & Management

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Ring sideroblast.
Heme synthesis.
Sideroblastic anemias: etiologic classification. DIDMOAD = diabetes insipidus, diabetes mellitus, optic atrophy, deafness.
Iron and total iron-binding capacity in physiology and pathology.

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Sideroblastic Anemias Workup

Approach Considerations

Complete Blood Cell Count and Peripheral Smear

Iron and Other Laboratory Studies

Additional Tests

Bone Marrow Aspiration and Biopsy

Histologic Findings

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