Hematology, Oncology & Immunology · Topic 1 of 26

Anemia Evaluation

Hematology · approach to anemia

Anemia Evaluation

Anemia is a sign, not a diagnosis: size the cells with the MCV, ask the marrow with the reticulocyte count, then test iron, B12 and folate.

Key numbers

Anemia: Hb below 13.6 (men), 12 (women)Hb < 13.6 ♂ / < 12 ♀

Sort anemia by MCVMCV < 80 or > 100 fL

Ferritin under 30 ng/mL means iron deficiencyferritin < 30 ng/mL

Reticulocyte production index under 2 = underproductionRPI < 2

01 · The numberSort anemia by MCV

Classify by MCV: microcytic below 80 fL (iron deficiency, thalassemia, some chronic disease), normocytic 80–100 fL (blood loss, chronic disease, kidney disease, hemolysis), macrocytic above 100 fL (B12 or folate deficiency, alcohol, liver disease, drugs).

02 · DoReticulocyte count: production or destruction?

Check the reticulocyte count with the CBC and smear: a high count means the marrow is compensating for hemolysis or bleeding; a low or normal count in anemia means underproduction.

03 · The numberFerritin under 30 ng/mL means iron deficiency

Serum ferritin below 30 ng/mL is specific for iron deficiency. Ferritin is an acute-phase reactant, so with inflammation, infection or cancer a ferritin up to 100 ng/mL is still compatible with iron deficiency.

Causes & risk factors

Why it happens

Chronic disease anemia: Hb usually above 8Anemia of chronic disease (infection, autoimmune disease, kidney disease, cancer) is normocytic then microcytic with a low reticulocyte count; Hb is usually above 8 g/dL, so a lower value suggests a second cause.

Presentation

What you'll see

Neuropathy and ataxia point to B12, not folatePeripheral neuropathy, paresthesias and gait instability occur only with B12 deficiency, can precede anemia, and become permanent if the deficiency persists; pernicious anemia (anti-intrinsic factor antibodies) is the most common cause.

High retic, LDH and bilirubin: suspect hemolysisAnemia with reticulocytosis, raised LDH and indirect bilirubin and low haptoglobin suggests hemolysis (work up with smear and direct antiglobulin test); with a normal LDH and bilirubin, suspect blood loss.

Diagnosis & monitoring

Work-up

Anemia: Hb below 13.6 (men), 12 (women) must knowAdult anemia = hemoglobin below 13.6 g/dL in men or below 12 g/dL in women. Anemia is a manifestation, not a diagnosis — even mild, asymptomatic anemia needs a cause.

Reticulocyte production index under 2 = underproductionRPI corrects the reticulocyte percentage for anemia: retic % × (Hct ÷ 45) ÷ maturation factor (1.0–2.5). RPI ≥ 2 is an adequate marrow response; below 2 means underproduction.

B12 under 200 pg/mL; borderline needs MMAB12 below 200 pg/mL or folate below 2 ng/mL is diagnostic; B12 of 200–300 pg/mL is indeterminate — check methylmalonic acid and homocysteine: both rise in B12 deficiency, only homocysteine in folate deficiency.

Management

Orders

No obvious source: evaluate the GI tract must knowIron deficiency usually means bleeding: men and postmenopausal women without an obvious source need GI evaluation, because anemia may be the only sign of an occult GI cancer. Never give iron without seeking the cause.

Give B12 1 mg IM for severe deficiencySevere B12 deficiency or neurologic signs: cyanocobalamin 1 mg IM 1–4 times weekly until counts correct, then monthly; milder deficiency: 1000–2000 mcg orally daily. Treatment is lifelong unless the cause is corrected.

Oral iron every other day; IV when neededGive 65 mg elemental iron (ferrous sulfate 325 mg) every other day; larger or more frequent doses raise hepcidin and side effects. Use IV iron for intolerance, failure, ongoing losses or urgent repletion.

More than one low cell line: marrow biopsyBone marrow aspiration and biopsy are reserved for unexplained anemia, more than one cytopenia (anemia plus leukopenia or thrombocytopenia), or a suspected primary marrow disorder such as leukemia, myeloma, aplastic anemia or myelodysplasia.

Red flags & don'ts

Avoid harm

Exclude B12 deficiency before giving folate avoidAlways exclude B12 deficiency before folate replacement: folate corrects the anemia of B12 deficiency but lets the neurologic damage progress.

Iron deficiency or anemia of chronic disease?

Commonly confused

Ferritin	Low — under 30 ng/mL
Total iron-binding capacity	High
Serum iron	Low
RBC size	Microcytic, high RDW
Treatment	Replace iron and find the bleeding source

Commonly confused

Tell apart

Microcytosis with normal iron: think thalassemiaIf iron studies exclude iron deficiency in a microcytic anemia, consider thalassemia (target cells, basophilic stippling; raised Hb A2 in beta-thalassemia on electrophoresis), anemia of chronic disease and sideroblastic anemia.

More detail

Reference

Show 5 reference facts

Megaloblastic anemia shows macro-ovalocytes, hypersegmented neutrophils, Howell-Jolly bodies, a high RDW and reticulocytopenia; later leukopenia and thrombocytopenia, with high LDH from ineffective erythropoiesis.

Nonmegaloblastic macrocytosis: alcohol (MCV about 100–105 fL), chronic liver disease, myelodysplasia, reticulocytosis, and drugs such as hydroxyurea and zidovudine.

Ferritin below 100 ng/mL in inflammation (below 200 ng/mL in chronic kidney disease) suggests iron deficiency on top of anemia of chronic disease.

After B12 replacement the reticulocyte count rises within 1 week and blood counts usually correct within 6 weeks; neurologic recovery is slower and may be incomplete.

Symptoms reflect speed of onset and cardiopulmonary reserve more than the number; pallor is common once hemoglobin falls below 7 g/dL, and severe anemia can cause high-output heart failure.

Pearl

Small cells: think iron first. Big cells: rule out B12 before you give folate.

Sources · Merck Manual Professional — Evaluation of Anemia · Merck Manual Professional — Iron Deficiency Anemia · Merck Manual Professional — Megaloblastic Macrocytic Anemias · Merck Manual Professional — Vitamin B12 Deficiency · Merck Manual Professional — Anemia of Chronic Disease · AMBOSS — Reticulocyte production index (RPI ≥ 2 adequate, < 2 hypoproliferative) · Merck Manual Professional — Overview of Hemolytic Anemia · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).