Sideroblastic Anemias Workup

Updated: Nov 18, 2015
  • Author: Muhammad A Mir, MD, FACP; Chief Editor: Emmanuel C Besa, MD  more...
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Workup

Approach Considerations

Workup may include a complete blood count (CBC), peripheral smear, iron studies (eg, ferritin and total iron-binding capacity [TIBC]), bone marrow aspiration and biopsy, and other studies as appropriate.

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Complete Blood Cell Count and Peripheral Smear

In patients with sideroblastic anemia, the CBC count usually reveals anemia, mostly moderate, although severe anemia has been reported. [63] The mean corpuscular volume (MCV) is usually low, with a microcytic picture; however, normocytic, macrocytic, [64] and classic dimorphic (normocytic + microcytic) [65] 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. [66] 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. [67]

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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. [68] Periodic iron studies are essential even for those who are not transfusion dependent.

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

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). [69] 4-PA can also be measured in urine.

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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.

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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.

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Histologic Findings

For an anemia to qualify as refractory anemia with ring sideroblasts (RARS) according to the National Comprehensive Cancer Network (NCCN) staging criteria, more than 15% of red blood cell precursors should be ring sideroblasts. The number of blasts should be less than 5% in the marrow and less than 1% in the peripheral blood. [70]

The term sideroblast has been loosely used in the literature. Koc and Harris have proposed that to be called a sideroblast, an erythroblast must exhibit more than 4 iron deposits, preferably lined around the nucleus (the pattern of distribution of mitochondria in juvenile cells), and the deposits should be large. [71] Ring sideroblasts contain insoluble iron complexes inside their mitochondria, demonstrable by electron microscopy, unlike the soluble ferritin/hemosiderin clusters that are found outside mitochondria in up to 60% of normal erythroid precursors.

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