STEPTRACKERHEMATOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Approach to Anemia

Two numbers sort almost every anemia: the MCV (cell size) and the reticulocyte response (is the marrow trying?).

FOCUS ON
Classify first: microcytic (< 80 fL) means a hemoglobin-synthesis problem, macrocytic (> 100 fL) means a DNA-synthesis or membrane problem. For normocytic, split by reticulocytes: low means underproduction, high means destruction or loss. The hemolysis lab panel shows up in every chapter after this.
CATEGORY
MECHANISM
KEY CAUSES
FIRST CLUE
Anemia — basics
↓ Hb / Hct
Less O₂-carrying capacity → tissue hypoxia, compensatory ↑ cardiac output.
Fatigue, pallor, dyspnea on exertion, tachycardia, flow murmur; high-output heart failure if severe
Pale conjunctivae and palmar creases
Microcytic
MCV < 80
Too little hemoglobin made → extra cell division → small, pale cells.
Iron deficiency, anemia of chronic disease (late), thalassemia, sideroblastic anemia (lead, B6, alcohol), copper deficiency
Iron studies decide — page 5.02
Normocytic, low retic
underproduction
Marrow can't respond.
Early iron deficiency or ACD, CKD (↓ EPO), aplastic anemia, marrow infiltration, pure red cell aplasia, hypothyroidism
Reticulocyte production index < 2
Normocytic, high retic
destruction or loss
Marrow responds to RBC loss.
Hemolysis (intrinsic or extrinsic), acute blood loss (after several days)
RPI > 3; polychromasia on smear
Macrocytic — megaloblastic
MCV > 100
Impaired DNA synthesis → nucleus lags behind cytoplasm.
B12 or folate deficiency; methotrexate, hydroxyurea, zidovudine, 5-FU; orotic aciduria
Hypersegmented neutrophils
Macrocytic — nonmegaloblastic
MCV > 100
Membrane lipid changes or immature cells — DNA synthesis is normal.
Alcohol, liver disease, hypothyroidism, reticulocytosis, MDS, Diamond-Blackfan anemia
No hypersegmented neutrophils
Reticulocyte count
marrow report card
Corrected retic = retic % × (Hct ÷ 45). RPI also divides by a maturation factor.
RPI > 3 = good response · < 2 = inadequate
Large bluish RBCs = polychromasia
Hemolysis panel
destruction signs
RBC contents spill or are processed by macrophages.
↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin, ↑ retic · intravascular adds hemoglobinuria, hemosiderinuria
Extravascular → splenomegaly, jaundice, gallstones
Blood loss
Acute: whole blood lost, so Hct is normal at first. Chronic: iron is lost.
Acute: normocytic, retic ↑ after ~5–7 days · chronic: iron-deficiency microcytosis
GI bleed, menorrhagia

Mechanism — the decision path

Anemia↓ Hb
→
MCV < 80Iron studies
→
Low ferritinIron deficiency
MCV 80–100Reticulocytes
→
LowProduction failure
HighHemolysis or bleed
MCV > 100Smear
→
HypersegsB12/folate (MMA, homocysteine)
NoneAlcohol, liver, thyroid, MDS

Lab hallmarks

TEST
MEANING
RDW ↑
Mixed cell sizes — iron deficiency (thal trait usually normal)
Mentzer index (MCV ÷ RBC)
< 13 → thalassemia trait · > 13 → iron deficiency
Ferritin ↓
Most specific single test for iron deficiency
Haptoglobin ↓
Free Hb bound and cleared — hemolysis
MMA + homocysteine
Both ↑ in B12 deficiency; only homocysteine ↑ in folate deficiency
Pancytopenia
Marrow failure, infiltration, hypersplenism, B12/folate

How it's tested

COMMON CONFUSIONAcute blood loss is normocytic, and the hematocrit is normal for the first hours because plasma and cells are lost together.
THE TRAPA raw reticulocyte percentage looks high in severe anemia simply because there are fewer RBCs. Correct it for hematocrit before calling the response adequate.
YOUR APPROACHMCV → (microcytic: iron studies · normocytic: retic · macrocytic: smear/B12/folate) → confirm the cause.

If you see… think…

Menstruating woman, MCV 72, ↑ RDW, ↓ ferritin → iron deficiency
MCV 66, high RBC count, normal RDW, Mentzer < 13 → thalassemia trait
Normocytic anemia, low retic, CKD → ↓ erythropoietin
Normocytic, ↑ retic, ↑ LDH, ↓ haptoglobin → hemolysis
MCV 115 with hypersegmented neutrophils → megaloblastic anemia
MCV 104 in a heavy drinker, no hypersegs → alcohol (nonmegaloblastic)
Teardrop cells + nucleated RBCs + immature WBCs → marrow infiltration or fibrosis
Pancytopenia with fatty, empty marrow → aplastic anemia
On hydroxyurea or methotrexate, MCV rises → DNA-synthesis inhibition