RBC Indices & Basics - Know Your Doughnuts

- MCV (Mean Corpuscular Volume): Average RBC size. Defines anemias:
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- Microcytic: <80 fL
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- Normocytic: 80-100 fL
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- Macrocytic: >100 fL
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- MCHC (Mean Corpuscular Hemoglobin Conc.): Avg. Hb concentration. ↑ in spherocytosis.
- RDW (Red Cell Distribution Width): Measures size variation (anisocytosis).
⭐ RDW is typically normal in thalassemia trait but elevated in iron deficiency anemia, helping differentiate these two microcytic anemias.
Microcytic Anemias - Small Cells, Big Problems
- Defined by Mean Corpuscular Volume (MCV) < 80 fL. Common causes are due to defective heme or globin synthesis.
- 📌 Mnemonic: TAILS
- Thalassemia
- Anemia of chronic disease
- Iron deficiency
- Lead poisoning
- Sideroblastic anemia

| Condition | Iron | TIBC | Ferritin | Key Features |
|---|---|---|---|---|
| Iron Deficiency | ↓ | ↑ | ↓ | Pica, koilonychia |
| Anemia of Chronic Disease | ↓ | ↓ | ↑ / N | ↑ Hepcidin |
| Thalassemias (α & β) | ↑ | N | ↑ | Target cells, normal RDW |
| Sideroblastic Anemia | ↑ | N | ↑ | Ring sideroblasts, basophilic stippling |
Macrocytic Anemias - Large & In Charge
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Anemia with Mean Corpuscular Volume (MCV) > 100 fL. Key division: Megaloblastic vs. Non-megaloblastic.
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Megaloblastic Anemia: Impaired DNA synthesis → delayed nuclear maturation.
- Causes: Folate (B9) & Cobalamin (B12) deficiency.
- Labs: ↑ Homocysteine. In B12 deficiency, also ↑ Methylmalonic Acid (MMA).
- Smear: Hypersegmented neutrophils (>5 lobes), macro-ovalocytes.
⭐ Neurological symptoms (subacute combined degeneration) are specific to B12 deficiency, not folate!
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Non-Megaloblastic Anemia: Normal DNA synthesis.
- Causes: Liver disease, alcoholism, hypothyroidism.

Normocytic Anemias - Just Right, Still Wrong
- Definition: Anemia with normal-sized red blood cells (MCV 80-100 fL), but ↓ total RBC count. The primary distinction is whether the bone marrow is responding appropriately (↑ reticulocytes).
- Hereditary Spherocytosis: Autosomal dominant defect in spectrin or ankyrin. Leads to loss of membrane, creating spherocytes. Diagnosed with osmotic fragility test. ↑ MCHC is characteristic.
⭐ Paroxysmal Nocturnal Hemoglobinuria (PNH): The only hemolytic anemia caused by an acquired genetic defect (PIGA gene). Presents with a classic triad of hemolytic anemia, pancytopenia, and venous thrombosis.
Polycythemia - Too Much of a Good Thing
- Definition: Increased RBC mass, with Hematocrit >49% in males, >48% in females.
- Primary (Polycythemia Vera): Neoplastic proliferation of myeloid cells.
- JAK2 V617F mutation is key.
- Features ↓ EPO, generalized pruritus (especially post-shower), plethora, and splenomegaly.
- Secondary: Response to ↑ EPO.
- Physiologic: High altitude, COPD.
- Pathologic: EPO-secreting tumors (Renal Cell Carcinoma).
- Relative: ↓ plasma volume (e.g., dehydration).
⭐ In Polycythemia Vera, despite low EPO levels, RBC production is autonomous and uncontrolled due to the JAK2 mutation.
High‑Yield Points - ⚡ Biggest Takeaways
- Iron deficiency anemia, the most common type, presents with microcytic, hypochromic cells and low ferritin.
- Anemia of chronic disease shows normocytic cells, high ferritin, and is driven by hepcidin.
- Megaloblastic anemias (B12/folate) feature macrocytic RBCs and hypersegmented neutrophils; only B12 causes neurologic deficits.
- Sickle cell anemia results from a β-globin point mutation, leading to vaso-occlusive crises and autosplenectomy.
- G6PD deficiency is an X-linked disorder causing hemolysis with oxidative triggers, showing Heinz bodies and Bite cells.
- Hereditary spherocytosis is an autosomal dominant defect causing spherocytes and an increased MCHC.
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