Anemia - Exam-Focused Notes

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1. Definition & Diagnostic Threshold

• Harrison's Principles, p. 492

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2. Classification

By MCV (Wintrobe Classification)

By Mechanism (Reticulocyte Count Guides You)

• Robbins & Kumar Basic Pathology, Table 14.1; Harrison's, p. 492

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3. Iron Deficiency Anemia (IDA)

Causes

• Chronic blood loss (most common in high-resource countries): GI (peptic ulcer, colon cancer, hemorrhoids), gynecologic (menorrhagia)
• Low dietary intake: vegetarian diet, infants fed exclusively milk, food insecurity
• Increased demand: pregnancy, infancy
• Malabsorption: celiac disease, gastritis, post-gastrectomy

Iron Metabolism Key Facts

• Total body iron: ~2.5 g (women), 3.5 g (men) - 80% in Hb/myoglobin/enzymes, 15-20% in storage (ferritin/hemosiderin)
• Iron transport: bound to transferrin (~33% saturation normally)
• Normal serum iron: 120 µg/dL (men), 100 µg/dL (women); TIBC: 300-350 µg/dL
• Hepcidin (liver peptide) is the master regulator - downregulates ferroportin, blocking iron release
• IL-6 (inflammation) raises hepcidin - explains anemia of chronic disease

Stages of Depletion (in order)

1. Ferritin drops (storage depleted)
2. Serum iron falls + transferrin rises (TIBC rises)
3. Hemoglobin falls → microcytic hypochromic anemia

Lab Pattern

Clinical Features

• Weakness, pallor, listlessness (usually mild/asymptomatic)
• Koilonychia (spoon nails) - long-standing cases
• Pica (craving nonfood items e.g. dirt/clay) - characteristic
• Peripheral smear: microcytic, hypochromic red cells; increased central pallor
• Platelet count often elevated (thrombocytosis)
• Robbins & Kumar Basic Pathology, pp. 393-394

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4. Anemia of Chronic Inflammation (ACI)

Causes

• Chronic infections (osteomyelitis, endocarditis, lung abscess)
• Chronic immune disorders (rheumatoid arthritis, Crohn's disease)
• Cancers (Hodgkin lymphoma, lung/breast carcinoma)

Pathogenesis

• Inflammation → IL-6 → ↑ hepcidin → downregulates ferroportin in marrow macrophages → iron trapped, unavailable to erythroblasts
• Also: blunted erythropoietin synthesis by the kidney

Treatment

• Treat the underlying disease (definitive)
• EPO + IV iron can temporize
• Robbins & Kumar Basic Pathology, p. 394

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5. Megaloblastic Anemia

Common Pathogenesis

Causes

Morphology (High-Yield)

• Macro-ovalocytes (oval macrocytes) - highly characteristic
• Hypersegmented neutrophils (≥5 lobes) - pathognomonic finding on smear
• Hypercellular bone marrow (but ineffective - cells undergo apoptosis)
• Giant metamyelocytes and band forms

B12 vs. Folate - Key Distinction

• Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 608-609

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6. Aplastic Anemia

Definition

Diagnosis Criteria

• Bone marrow cellularity <25% (or <50% with <30% hematopoietic cells)
• Peripheral blood shows pancytopenia with relative lymphocytosis

Severity Classification

Causes (Acquired)

• Idiopathic (~70%) - autoimmune T-cell destruction of stem cells
• Drugs (chloramphenicol, NSAIDs, sulfonamides), toxins (benzene)
• Viral (hepatitis, EBV, CMV, HIV, parvovirus B19)
• Radiation

Congenital

• Fanconi anemia (DNA repair defects, chromosome fragility)
• Telomerase defects (dyskeratosis congenita)
• Goldman-Cecil Medicine, p. 1736; Robbins Basic Pathology, Table 14.1

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7. Hemolytic Anemias - Overview

Hallmarks of Hemolysis

• ↑ unconjugated (indirect) bilirubin → jaundice
• ↑ LDH
• ↓ haptoglobin (binds free Hb)
• Reticulocytosis (bone marrow compensation)
• Hemoglobinuria (intravascular hemolysis)
• Splenomegaly (extravascular)
• Pigment gallstones (chronic hemolysis)

Hereditary Spherocytosis (HS)

• Defect in spectrin, ankyrin, band 3 proteins → loss of membrane → spherocyte
• Extravascular hemolysis in the spleen (spherocytes can't deform to exit splenic cords)
• Smear: small, hyperchromic spherocytes, no central pallor
• Diagnosis: spherocytosis + reticulocytosis + negative direct Coombs (distinguishes from AIHA) + ↑ MCHC
• Confirmatory: eosin-5'-maleimide (EMA) dye binding (decreased)
• Treatment: splenectomy corrects anemia (spherocytes persist but aren't destroyed)
• Complication: pigment gallstones in 40-50% of adults

G6PD Deficiency

• X-linked recessive; protects against malaria
• Oxidant stress (infection, drugs, fava beans) → Heinz bodies → intravascular hemolysis
• Smear: Heinz bodies, bite cells

Sickle Cell Disease

• Point mutation: Glu → Val at position 6 of β-globin → HbS
• Deoxygenation → HbS polymerizes → rigid, sickle-shaped cells
• Vaso-occlusive crisis triggered by hypoxia (altitude, infection), dehydration, cold
• Complications: stroke, acute chest syndrome, splenic sequestration, avascular necrosis, dactylitis (hand-foot syndrome in infants), autosplenectomy → susceptibility to encapsulated organisms
• Treatment: hydroxyurea (↑ HbF), exchange transfusion, hematopoietic stem cell transplant
• Robbins, Cotran & Kumar, pp. 597-609

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8. High-Yield Comparison Table

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9. Quick Reference: MCV-Based Approach to Workup

Anemia detected
│
├─ MCV LOW (microcytic)
│   → Check: Ferritin, TIBC, serum iron
│   → IDA (↓ferritin), ACI (↑ferritin), Thalassemia (target cells, ↑HbA2)
│
├─ MCV NORMAL (normocytic)
│   → Check reticulocyte count
│   → High retic → hemolysis or acute blood loss
│   → Low retic → aplastic anemia, CKD, myelophthisis
│
└─ MCV HIGH (macrocytic)
    → Check B12 and folate levels
    → Oval macrocytes + hyperseg neutrophils → megaloblastic
    → Round macrocytes → alcohol, liver disease, hypothyroidism

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