Anemia Workup: Micro, Normo, Macro Algorithms

A practical pathway beginning with CBC indices and a reticulocyte count, then branching by MCV: microcytic, normocytic, or macrocytic. Use pattern recognition plus targeted tests to find cause, treat safely, and set follow-up.

Start with the Basics

• Confirm anemia: Compare Hb/Hct with lab reference and baseline; check trend.
• Get reticulocyte count (production vs. destruction/loss) and MCV (micro/normo/macro).
• Review meds (anticoagulants, chemo, antiretrovirals, linezolid, metformin), alcohol, diet, pregnancy, bleeding.

Microcytic (MCV < 80 fL)

• First-line labs: Ferritin, serum iron, TIBC/transferrin, transferrin saturation (TSAT).
• Iron deficiency (ID): low ferritin (<30 ng/mL is highly specific; 30–100 can be ID if CRP high), low TSAT.
• Anemia of chronic inflammation (ACI): normal/high ferritin with low iron and low TSAT.
• Thalassemia trait: very low MCV with normal/high RBC count; normal iron studies; confirm with hemoglobin electrophoresis or DNA when indicated.
• Next steps in ID: identify source—GI bleed common in adults. Consider fecal occult blood, celiac screen, and endoscopy/colonoscopy per age/risk.

Normocytic (MCV 80–100 fL)

• Low retic: underproduction—CKD (check eGFR), endocrine (TSH), marrow disease (consider smear, LDH; if pancytopenia, hematology).
• High retic: loss/destruction—hemolysis or bleeding. Order LDH, indirect bilirubin, haptoglobin, Coombs, and review smear (spherocytes, schistocytes).
• Acute bleed can be normocytic early; trend Hb and iron stores later.

Macrocytic (MCV > 100 fL)

• Megaloblastic: B12 or folate deficiency. Check B12, folate; if B12 borderline, add methylmalonic acid ± homocysteine.
• Non-megaloblastic: alcohol, liver disease, hypothyroidism, reticulocytosis, meds (hydroxyurea, MTX), myelodysplasia.
• Treat B12 before folate when both suspected to avoid masking neurologic injury.

Iron Therapy: Oral vs. IV

• Oral elemental iron: ~40–65 mg once daily or every other day (better absorption/tolerance than TID); take with vitamin C, away from calcium/PPIs.
• IV iron: use for malabsorption, intolerance, severe deficiency needing rapid repletion, active IBD, CKD on ESA, or after bariatric surgery.
• Expect retic rise in 7–10 days and Hb ↑ ~1 g/dL every 2–3 weeks once iron is replaced and bleeding controlled.

Transfusion & ESA Pearls

• Transfuse for hemodynamic instability, active ischemia, or Hb generally <7 g/dL (institutional thresholds vary; higher in ACS, pregnancy, perioperative).
• ESAs in CKD: consider when Hb persistently <10 g/dL after iron repletion; weigh CV risk; aim for conservative targets.

Algorithm Snapshot

1. CBC + retic → classify by MCV.
2. Micro: iron studies → ID vs. ACI vs. thalassemia; if ID, find bleeding source.
3. Normo: retic low = underproduction (CKD, endocrine, marrow); retic high = hemolysis/bleed (do hemolysis panel).
4. Macro: B12/folate ± MMA; consider alcohol, liver, thyroid, meds, MDS.

Red Flags (Escalate/Hematology)

• Pancytopenia, blasts on smear, schistocytes, rapidly falling Hb, or severe hemolysis.
• Unexplained iron deficiency in men/postmenopausal women (evaluate GI tract).
• Neurologic symptoms with suspected B12 deficiency.

Patient FAQs

“How fast will I feel better on iron?” Fatigue often improves within weeks; full repletion and ferritin recovery take months.

“Why does my MCV stay high?” Alcohol, meds, or reticulocytosis can keep it high even as Hb rises—track trends and causes.

References & Notes

This pathway reflects standard internal medicine and hematology practice. Local protocols and thresholds vary—follow institutional guidance. Educational only.