Differentials

Anaemia of chronic disease

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Signs and symptoms of underlying chronic disease (e.g., infection, cancer, autoimmune disease, kidney disease).

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FBC and peripheral smear: anaemia, hypochromia, microcytosis, anisocytosis, and poikilocytosis are less pronounced than in IDA.

In 80% of cases, anaemia of chronic disease is normocytic and normochromic. However, in 20% of cases it can present as a microcytic, hypochromic anaemia similar to IDA.

Ferritin is often elevated in patients with anaemia of chronic disease.[103]

Anaemia of chronic disease has a normal transferrin receptor assay.[103] Therapeutic trial of iron does not increase Hb.

Disorders of globin synthesis (thalassaemias, haemoglobin E, haemoglobin C, unstable haemoglobins)

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Patients with severe thalassaemia are usually transfusion dependent from childhood and therefore diagnosed early. Patients with thalassaemia minor may not be diagnosed until adulthood.

Haemoglobin electrophoresis may help distinguish these disorders but can be normal.

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FBC: often more severe microcytosis than expected for the degree of anaemia.

Haemoglobin: usually reduced.

Red cell distribution width: usually normal in thalassaemia.

Peripheral smear: more pronounced basophilic stippling and target cells.

Haemoglobin electrophoresis: raised haemoglobin A2 level is a common beta-thalassaemia trait.

Sideroblastic anaemias

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Alcoholism can be a cause of a reversible sideroblastic anaemia. Hepatosplenomegaly is found in one third to one half of patients with sideroblastic anaemia and is not present in IDA.[4]

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Peripheral smear: erythrocyte dimorphism (hypochromic, microcytic population mixed with normal population); erythrocyte dimorphism is also seen in partially treated IDA.

Presence of the occasional heavily stippled, hypochromic cell.[4]

Bone marrow biopsy: ringed sideroblasts seen because of accumulation of iron in the mitochondria.

Disorders of porphyrin and haem synthesis

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A collection of disorders characterised by defective synthesis of porphyrin and haem.

A positive family history may be present. Neurological disorders and/or photosensitivity may be present.

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Testing for most of these disorders is not readily available.

Referral to a haematologist and/or research centre may be necessary.

Lead intoxication

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Patients may have a history of risk factors for lead exposure such as occupational exposures (exposure to lead paint) or distillation of illicit (illegally produced homemade) alcohol.

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Lead level and free erythrocyte protoporphyrin (FEP) or zinc protoporphyrin (ZPP) can be tested. Lead level is increased. Increased FEP or ZPP can reflect exposure to lead in previous 3 months (the typical lifespan of a red cell).

Atransferrinaemia

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Very rare disorder characterised by low plasma iron concentration secondary to a lack of transferrin, which normally acts as a specific iron transport protein.

Transferrin can be given to correct the disorder.[4]

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Serum and bone marrow iron levels: low as they are in IDA, but, unlike in IDA, total iron-binding capacity will also be low.[4]

Antibodies against the transferrin receptor

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Case reports exist, but very rare.[106]

Clinically, these patients resemble patients with IDA.

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Iron profile: increased serum iron concentration, normal serum ferritin level.

FEP: dramatically increased.[4]

Aluminium intoxication

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Occurs primarily in haemodialysis patients if the public water supply is used as a source of water for dialysis.

Can be avoided with the use of deionised water and can be reversed with the use of a deferoxamine chelator.[4]

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Erythrocyte aluminium levels increased.[4]

Copper deficiency (hereditary aceruloplasminaemia)

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Patients often have neurological abnormalities.[107]

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Microcytic anaemia, increased ferritin, and no serum ceruloplasmin.[107]

Gallium administration

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History of gallium infusion.

Used as diagnostic and therapeutic agent in cancer, and disorders of calcium and bone metabolism.

Gallium binds to transferrin and inhibits cellular iron uptake.

Microcytic hypochromic anaemia has been reported in patients treated with gallium in clinical trials.[108]

INVESTIGATIONS

History of gallium administration.

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