Differentials
Iron deficiency anemia
SIGNS / SYMPTOMS
Signs and symptoms of anemia may be identical to those of anemia of chronic disease (ACD). Evidence of bleeding, or a compelling cause for poor iron absorption, may be found in iron deficiency, whereas these are absent in ACD.
INVESTIGATIONS
Ferritin is typically low in iron deficiency and normal or elevated (>100 nanograms/mL) in anemia of chronic disease (ACD). A ferritin level of <15 nanograms/mL strongly suggests iron deficiency, although different thresholds have been used (30 or 50 nanograms/mL).
The transferrin saturation is typically <20% in iron deficiency; a value of <5% makes iron deficiency very likely.
Total iron-binding capacity is typically elevated in iron deficiency anemia (IDA) (>400 micrograms/dL) and reduced (<250 micrograms/dL) in ACD.
Soluble transferrin receptor (sTfR) is elevated in iron deficiency and normal in ACD.[17] The ratio of sTfR (mg/L) to log ferritin (micrograms/L) is >2 in iron deficiency.[39]
Bone marrow iron is absent in IDA.
Iron deficiency anemia coexisting with ACD
SIGNS / SYMPTOMS
There may be no differentiating symptoms or signs.
INVESTIGATIONS
Ferritin is less helpful and can be <100 nanograms/mL in iron deficiency anemia (IDA). Ferritin between 100 and 300 nanograms/mL and a serum transferrin saturation of <20% can represent anemia of chronic disease with concomitant IDA.[30][50]
Soluble transferrin receptor (sFTR) is normal to increased. Ratio of sTfR to log ferritin is high (>2) when IDA and ACD coexist.[39]
Anemia associated with chronic renal disease (erythropoietin deficiency)
SIGNS / SYMPTOMS
Symptoms and signs may be identical to those of anemia of chronic disease (ACD).
Patient more likely to present with conditions related to chronic renal disease (e.g., diabetes, hypertension, polycystic kidney disease).
Patients with end-stage renal disease, including those on dialysis, may have ACD in addition to anemia of renal disease.
INVESTIGATIONS
Serum creatinine is typically at least mildly elevated. Rarely, only creatinine clearance is reduced, as in early diabetic chronic kidney disease.
When ACD coexists with anemia of renal disease, ferritin (absent in iron deficiency) should be higher than otherwise, and C-reactive protein and erythrocyte sedimentation rate should be elevated.
B12 deficiency (e.g., pernicious anemia)
SIGNS / SYMPTOMS
History of diet poor in vitamin B12, inflammatory bowel disease, or gastric bypass surgery.[4]
Posterior column symptoms and signs (e.g., ataxia, gait abnormalities) may be present.
Occasionally may be other neurologic symptoms and signs (e.g., peripheral neuropathy).
INVESTIGATIONS
Anemia is typically macrocytic (MCV >100 fL).
Serum B12 is low (<200 picograms/mL).
Folate deficiency
SIGNS / SYMPTOMS
History of diet poor in folate, inflammatory bowel disease, or heavy alcohol use.[4]
INVESTIGATIONS
Anemia is macrocytic (MCV >100 fL).
Low serum folate (<2.5 nanograms/mL).
Red blood cell folate level <140 nanograms/mL.
Thalassemia
SIGNS / SYMPTOMS
The patient is more likely to have a family history of thalassemia.
More common in certain ethnic groups (Mediterranean, south Asian, or east Asian ancestry).
INVESTIGATIONS
Mean corpuscular volume is low and mean corpuscular hemoglobin concentration is relatively normal in thalassemia trait, and Hb A2 is increased.
Blood smear shows microcytosis and significant poikilocytosis.
Anemia due to drugs, radiation, and chemical exposure
SIGNS / SYMPTOMS
Appropriate history of exposure to radiation, chemicals, or medication, especially having recently started to take a drug known to cause anemia.
INVESTIGATIONS
Bone marrow exam may show incipient or fully developed aplastic anemia.
Absolute reticulocyte count is typically low for the degree of anemia in hypoplastic and aplastic anemia.
Primary hematologic disorder (e.g., myelodysplasia, multiple myeloma, leukemia, lymphoma)
SIGNS / SYMPTOMS
Bone pain, history of recent fracture, purpura, ecchymoses, lymphadenopathy, hepatomegaly, splenomegaly are all more likely with primary hematologic disorder than with anemia of chronic disease.
INVESTIGATIONS
Mean corpuscular volume normal or mildly increased. CBC may show leukopenia, granulocytopenia, thrombocytopenia, leukocytosis, or thrombocytosis. Peripheral smear may show precursor cells. Lactate dehydrogenase may be increased.
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