Differentials

Anemia of chronic disease

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

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

INVESTIGATIONS

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

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

Ferritin is often elevated in patients with anemia of chronic disease.[105]

Anemia of chronic disease has a normal transferrin receptor assay.[105] Therapeutic trial of iron does not increase Hb.

Disorders of globin synthesis (thalassemias, hemoglobin E, hemoglobin C, unstable hemoglobins)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

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

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

INVESTIGATIONS

CBC: often more severe microcytosis than expected for the degree of anemia.

Hemoglobin: usually reduced.

Red cell distribution width: usually normal in thalassemia.

Peripheral smear: more pronounced basophilic stippling and target cells.

Hemoglobin electrophoresis: elevated hemoglobin A2 level is a common beta-thalassemia trait.

Sideroblastic anemias

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

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

INVESTIGATIONS

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 heme synthesis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

A collection of disorders characterized by defective synthesis of porphyrin and heme.

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

INVESTIGATIONS

Testing for most of these disorders is not readily available.

Referral to a hematologist and/or research center may be necessary.

Lead intoxication

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

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.

INVESTIGATIONS

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).

Atransferrinemia

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Very rare disorder characterized 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]

INVESTIGATIONS

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

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Case reports exist, but very rare.[108]

Clinically, these patients resemble patients with IDA.

INVESTIGATIONS

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

FEP: dramatically increased.[4]

Aluminum intoxication

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

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

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

INVESTIGATIONS

Erythrocyte aluminum levels increased.[4]

Copper deficiency (hereditary aceruloplasminemia)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Patients often have neurologic abnormalities.[109]

INVESTIGATIONS

Microcytic anemia, increased ferritin, and no serum ceruloplasmin.[109]

Gallium administration

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

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 anemia has been reported in patients treated with gallium in clinical trials.[110]

INVESTIGATIONS

History of gallium administration.

Use of this content is subject to our disclaimer