Key discriminator: Ferritin is an acute-phase reactant. If ferritin is ambiguous (30–100 ng/mL) with concurrent inflammation (CRP↑), use soluble transferrin receptor (sTfR) or sTfR/log-ferritin index — not affected by inflammation.
Iron studies interpretation
| Parameter | Adult ref range | Iron deficiency | Anemia of chronic disease | Mixed (both) |
|---|---|---|---|---|
| Serum Iron | 65–175 µg/dL | ↓ | ↓ | ↓ |
| TIBC | 240–450 µg/dL | ↑ or high-normal | ↓ or normal | Normal |
| Transferrin | 200–360 mg/dL | ↑ | Normal/↓ | Normal |
| TSAT (Fe/TIBC ×100) | 20–50% | <15–20% | Normal or low-normal | Low |
| Ferritin | M 24–336, F 11–307 ng/mL | ↓ (<30, often <15) | Normal/↑ | Normal ("falsely corrected") |
| sTfR | assay-dependent | ↑ | Normal | ↑ |
| sTfR/log ferritin index | <1 vs >2 | High index | Low index | Intermediate |
TSAT calculator
Interpretation logic
Ferritin low (<30 ng/mL)?
↓
YesTrue iron deficiency — high specificity regardless of inflammation.
Ambiguous (30–100)Check CRP. If inflamed → check sTfR or sTfR/log-ferritin index.
Normal/HighConsider ACD, inflammation, or iron overload if TSAT also high.
In elderly patients, new iron deficiency mandates evaluation for occult GI blood loss (EGD/colonoscopy) unless another clear source is identified.
Reticulocyte indices
| Metric | Formula | Normal | Use |
|---|---|---|---|
| Retic % | measured | 0.5–2.5% | Raw automated/manual count |
| Absolute retic count | Retic % × RBC count (×10⁶/µL) × 10 | 25,000–100,000/µL | More reliable than %, avoids denominator bias in anemia |
| Corrected retic % | Retic % × (Pt Hct ÷ 45) | — | Corrects for degree of anemia |
| RPI | Corrected retic % ÷ Maturation factor | <2 hypoproliferative; >2–3 appropriate response | Marrow failure vs peripheral loss/hemolysis |
Maturation factor (shift correction): Hct 40%=1.0 · 30%=1.5 · 20%=2.0 · 10%=2.5
RPI calculator
RPI <2Hypoproliferative — marrow not responding appropriately. Consider iron/B12/folate deficiency, marrow suppression, renal disease, ACD.
RPI >2–3Appropriate marrow response — implies peripheral loss (hemolysis, acute bleeding).
Stepwise approach to anemia
Step 1 · Classify by MCV (fL)
↓
Microcytic <80Iron deficiency, thalassemia trait, ACD (sometimes), sideroblastic
Normocytic 80–100Early IDA/ACD, renal disease, hemolysis, aplastic, mixed nutritional
Macrocytic >100B12/folate deficiency, hypothyroidism, liver disease, MDS, reticulocytosis, alcohol, drugs (hydroxyurea, MTX)
↓
Step 2 · Reticulocyte count (absolute + RPI)
↓
Hypoproliferative (RPI <2)Marrow-production problem → targeted deficiency/marrow workup
Hyperproliferative (RPI >2)Peripheral loss → hemolysis or bleeding workup
↓
Step 3 · Targeted workup by branch
Step 3 detail
Hypoproliferative + microcytic
- Iron studies: Fe / TIBC / TSAT / ferritin ± sTfR
Hypoproliferative + macrocytic
- B12, folate, TSH
- Peripheral smear: hypersegmented neutrophils, oval macrocytes
- LFTs
Hyperproliferative (RPI >2)
- Hemolysis panel: LDH↑, haptoglobin↓, indirect bilirubin↑
- Peripheral smear: schistocytes, spherocytes
- Direct antiglobulin test (Coombs)
- Or evaluate for acute/occult bleeding source
Normocytic, uncertain
- Consider combined deficiency
- Renal function (EPO deficiency), CKD staging
- Bone marrow biopsy if cytopenias/blasts present
Step 4–5
Always: peripheral smear
Cheap, high-yield. RBC morphology (microcytic hypochromic, target cells, schistocytes, spherocytes, teardrop, basophilic stippling); WBC/platelet abnormalities suggesting marrow process.
Confirm etiology → treat the cause
Not just the anemia — e.g., iron deficiency in an elderly patient mandates GI source workup, not just iron replacement.
Hemolysis panel
| Test | Finding in hemolysis | Notes |
|---|---|---|
| LDH | ↑ | Nonspecific, released from lysed RBCs |
| Haptoglobin | ↓ (often undetectable) | Binds free Hb; consumed in intravascular hemolysis |
| Indirect bilirubin | ↑ | From heme catabolism |
| Retic count / RPI | ↑ (RPI >2–3) | Appropriate marrow response |
| Peripheral smear | Schistocytes (MAHA), spherocytes (immune/hereditary spherocytosis) | Morphology narrows differential |
| DAT (Coombs) | Positive in immune-mediated hemolysis | Negative → consider hereditary (G6PD, spherocytosis) or mechanical (MAHA, prosthetic valve) |
| Urine hemosiderin/hemoglobin | Positive in intravascular hemolysis | Chronic intravascular loss |
DAT (Coombs) result
↓
PositiveImmune-mediated: autoimmune hemolytic anemia (warm/cold), drug-induced, transfusion reaction
NegativeConsider hereditary (G6PD deficiency, hereditary spherocytosis, hemoglobinopathy) or mechanical (MAHA — TTP/HUS/DIC, prosthetic valve, march hemolysis)