🧬 RBC morphology
- Anisocytosis – unequal size
- Poikilocytosis – abnormal shape
- Elliptocytes – hereditary elliptocytosis
- Spherocytes – ↓ membrane; HS, AIHA
- Target cells – ↑ membrane; thalassemia, liver disease
- Acanthocytes – irregular spicules; abetalipoproteinemia
- Echinocytes – smooth undulations; uremia / artifact
- Schistocytes – fragments; MAHA, traumatic hemolysis
- Bite cells – “bites” removed by spleen; G6PD
- Teardrop cells – myelofibrosis, thalassemia
- Sickle cells – HbS, sickle cell anemia
- Rouleaux – “stack of coins”; multiple myeloma
- Inclusions
- Basophilic stippling – RNA remnants; lead poisoning / reticulocytosis
- Howell-Jolly bodies – nuclear remnants; asplenia
- Pappenheimer bodies – iron; post-splenectomy
- Ring sideroblasts – iron-laden mitochondria; sideroblastic anemia
- Heinz bodies – denatured Hb; G6PD (supravital stain)
- Heinz bodies are not visible on Wright-Giemsa; use methylene blue / crystal violet.
🩸 Anemia · general concepts
- Definition – reduced circulating RBC mass
- Signs – pallor, fatigue, dizziness, angina, claudication
- Oxygen content – ↓ Hb → ↓ content; SaO₂ & PaO₂ remain normal
- Reticulocytes
- Immature, larger, polychromatic (RNA)
- Maturation: ~1 day
- Normal count: 0.5–1.5%
- Corrected reticulocyte count = (patient Hct / 45) × reticulocyte %
- Reticulocyte production index = corrected count / 2 (shift cells present)
| Index | Meaning |
|---|---|
| MCV | mean corpuscular volume |
| MCH | mean Hb per RBC |
| MCHC | mean Hb concentration |
| RDW | anisocytosis (variation in volume) |
- Classification by color
- Normochromic – normal central pallor
- Hypochromic – increased central pallor
- Hyperchromic – spherocytosis (loss of pallor)
- Pathogenesis categories
- Blood loss
- Hemolytic (hereditary, immune, acquired)
- Diminished erythropoiesis (megaloblastic, iron deficiency, AOCD, aplastic, sideroblastic)
🔴 Microcytic anemias
- Iron deficiency
- Iron physiology: Hb, myoglobin, enzymes; ferritin (storage), hemosiderin (Prussian blue +)
- Transport: transferrin; saturation = serum iron / TIBC × 100
- Causes: ↓ intake, ↑ demand, ↓ absorption (gastrectomy, malabsorption), chronic blood loss
↓ ferritin→
↓ serum Fe→
↑ TIBC→
↓ % sat→
microcytic/hypochromic
- Clinical: koilonychia, pica, Plummer-Vinson (dysphagia + glossitis)
| Parameter | Iron deficiency | AOCD | Thalassemia minor |
|---|---|---|---|
| Serum iron | ↓ | ↓ | Normal |
| TIBC | ↑ | ↓ | Normal |
| % saturation | ↓ | ↓ | Normal |
| Ferritin | ↓ | ↑ (or normal) | Normal |
- Anemia of chronic disease (AOCD) – IL-6 ↑ hepcidin → Fe trapped in macrophages
- Thalassemia – quantitative Hb defect
- α-thalassemia: gene deletions (4 genes)
- silent carrier (1 deletion) – asymptomatic
- trait (2 deletions) – mild anemia
- HbH (3 deletions) – Heinz bodies, microcytic
- hydrops fetalis (4 deletions) – lethal
- β-thalassemia: point mutations (2 genes)
- minor (1 mutation) – ↑HbA₂, ↑HbF
- intermedia – variable
- major (Cooley) – severe, transfusion-dependent, crew-cut skull, chipmunk facies
- α-thalassemia: gene deletions (4 genes)
- Sideroblastic – ring sideroblasts; ↑ Fe, ↑ ferritin, ↓ TIBC; B₆-responsive or MDS
- Thalassemia minor: normal ferritin, normal or ↑ serum iron, ↑ RDW not required.
⚪ Normocytic anemias
- Acute blood loss – hemodilution, reticulocytosis at 5–7 days
- Chronic blood loss – leads to iron deficiency
- Hemolytic anemias
- Intravascular – hemoglobinemia, hemoglobinuria, ↓ haptoglobin, no splenomegaly
- Extravascular – splenomegaly, ↑ bilirubin, ↓ haptoglobin (less)
- Sickle cell disease – HbS (Glu6Val); homozygous SS
- Precipitants: dehydration, acidosis, ↓ HbF
- Complications: vaso-occlusive crisis, autosplenectomy, aplastic crisis (parvovirus B19), acute chest, priapism
- Treatment: hydroxyurea (↑ HbF), stem cell transplant
- HbC disease – mild anemia, target cells, rod-shaped crystals
- G6PD deficiency – X-linked; oxidative stress → Heinz bodies → bite cells
- African variant (A–) – intermittent, older cells affected
- Mediterranean – favism, severe
- Hereditary spherocytosis – ankyrin/spectrin defect; osmotic fragility ↑; Coombs negative
- AIHA (warm) – IgG anti-Rh; Coombs positive; spherocytes
- PNH – PIGA mutation, complement-mediated, nocturnal hemolysis, pancytopenia, thrombosis
- Pyruvate kinase deficiency – ↓ ATP, hemolysis, ↑ 2,3-BPG (right shift)
- Hereditary elliptocytosis – spectrin defect, oval cells
- Aplastic anemia – pancytopenia; drugs, chemicals, viruses, radiation
- Direct Coombs test differentiates AIHA (positive) from hereditary spherocytosis (negative).
🔵 Macrocytic anemias
- Megaloblastic – impaired DNA synthesis (nuclear-cytoplasmic asynchrony)
- Macro-ovalocytes, hypersegmented neutrophils (>5 lobes), giant metamyelocytes
- ↑ LDH, ↑ indirect bilirubin (ineffective erythropoiesis)
- B₁₂ deficiency
- Causes: pernicious anemia, gastrectomy, pancreatic insufficiency, ileal malabsorption
- Neurologic: subacute combined degeneration (posterior + lateral columns) – loss of vibration/position, spasticity, ataxia
- Labs: ↓ B₁₂, ↑ homocysteine, ↑ methylmalonic acid
- Folate deficiency
- Causes: ↓ intake, malabsorption, ↑ demand, methotrexate
- No neurologic symptoms
- Labs: ↓ folate, ↑ homocysteine (MMA normal)
B12 + haptocorrin→
pancreatic proteases→
IF (parietal cell)→
ileal absorption
- B₁₂ deficiency causes neurologic deficits; folate does not.
📈 Polycythemia
- Polycythemia vera – clonal myeloid stem cell; ↑ RBC mass, often pancytosis
- Secondary – ↑ erythropoietin (hypoxia: COPD, cyanotic heart disease; or tumor: RCC)
- Relative – ↓ plasma volume (dehydration); normal RBC mass, normal EPO
- Polycythemia vera: consider JAK2 mutation, low EPO, risk of thrombosis.