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ANEMIA - Complete University Exam Notes (MBBS)

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DEFINITION

• Adult males: < 13 g/dL
• Adult females: < 12 g/dL
• Pregnant women: < 11 g/dL

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CLASSIFICATION OF ANEMIA

A. Pathophysiologic Classification (Most Important for Exams)

B. Morphologic Classification (MCV-based - Clinically Useful)

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1. IRON DEFICIENCY ANEMIA (IDA)

Epidemiology

Causes (in order of frequency)

1. Inadequate diet - most common in developing countries
2. Chronic blood loss - most common in developed countries
   • GI tract lesions (peptic ulcer, colon cancer, hookworm)
   • Menorrhagia in females
3. Increased demand - pregnancy, infancy, rapid growth
4. Malabsorption - celiac disease, gastrectomy

Iron Metabolism (Key Points)

• Daily dietary iron: 10-20 mg; only 1-2 mg absorbed
• Heme iron (animal): ~20% absorbed; Non-heme iron (vegetable): only 1-2% absorbed
• Absorbed in proximal duodenum as Fe²⁺ via DMT1 transporter
• Transported across basolateral membrane by ferroportin
• Carried in blood by transferrin
• Stored as ferritin (normal form) and hemosiderin (overload)
• Regulated by hepcidin - a liver peptide that inhibits ferroportin

• High iron / inflammation → ↑ Hepcidin → ↓ Ferroportin → ↓ Iron absorption
• Low iron / anemia → ↓ Hepcidin → ↑ Ferroportin → ↑ Iron absorption

Stages of IDA

1. Pre-latent: Only storage iron depleted (↓ serum ferritin). No anemia yet.
2. Latent: Storage + transport iron depleted (↓ ferritin, ↓ serum iron, ↑ TIBC). No anemia yet.
3. Manifest IDA: Frank anemia with symptoms.

Lab Findings

Clinical Features

• Fatigue, pallor, weakness, dyspnea
• Pica (craving for clay/ice = pagophagia)
• Angular stomatitis, atrophic glossitis
• Koilonychia (spoon nails)
• Plummer-Vinson syndrome (IDA + dysphagia + esophageal webs - females)

Treatment

• Treat underlying cause
• Oral ferrous sulfate 200 mg TDS × 3-6 months (continue 3 months after Hb normalizes to replenish stores)
• IV iron if intolerance or malabsorption

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2. MEGALOBLASTIC ANEMIA

Definition

Causes

Pernicious Anemia (Most Important B12 Cause)

• Autoimmune destruction of gastric parietal cells → ↓ Intrinsic Factor (IF)
• Without IF, B12 cannot be absorbed in terminal ileum
• Associated with anti-IF antibodies and anti-parietal cell antibodies
• Older age; Northern European descent
• Associated with achlorhydria

Morphology (HIGH YIELD)

• Peripheral blood: Macro-ovalocytes, hypersegmented neutrophils (≥5 lobes) - PATHOGNOMONIC
• Bone marrow: Megaloblasts, giant metamyelocytes

Lab Findings

Neurological Features (B12 only)

• Demyelination of posterior columns (loss of vibration, proprioception)
• Demyelination of lateral corticospinal tracts (UMN signs - spasticity, hyperreflexia)
• Peripheral neuropathy
• Psychiatric symptoms (megaloblastic madness)

Treatment

• B12 deficiency: Hydroxocobalamin IM (monthly, often lifelong in pernicious anemia)
• Folate deficiency: Oral folic acid 5 mg/day
• NEVER give folate alone without ruling out B12 deficiency - corrects anemia but worsens neurological damage

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3. HEMOLYTIC ANEMIA

Definition

General Features of All Hemolytic Anemias

• Marrow erythroid hyperplasia + Reticulocytosis (compensatory)
• Elevated serum LDH
• Elevated indirect bilirubin (hyperbilirubinemia)
• Decreased haptoglobin (in both intra and extravascular hemolysis)
• Extramedullary hematopoiesis (liver, spleen, lymph nodes in severe cases)

Classification

By Site of Hemolysis:

By Cause (Intrinsic vs Extrinsic):

• RBC membrane: Hereditary spherocytosis, elliptocytosis
• Enzyme defects: G6PD deficiency, Pyruvate kinase deficiency
• Hemoglobin defects: Sickle cell disease, Thalassemia

• Immune: Autoimmune hemolytic anemia, transfusion reactions, hemolytic disease of newborn
• Microangiopathic: HUS, TTP, DIC
• Infections: Malaria, Babesiosis
• Drugs, toxins
• Mechanical: Defective heart valves, marathon running

Key Individual Hemolytic Anemias

Hereditary Spherocytosis (HS)

• Defect: Mutations in spectrin, ankyrin, or band 3 proteins → unstable RBC membrane → spherocytes
• Inheritance: Autosomal dominant (mostly)
• Smear: Spherocytes (no central pallor)
• Test: Osmotic fragility test (increased), Acidified glycerol lysis test, EMA binding test
• Features: Anemia, jaundice, splenomegaly (classic triad), pigment gallstones
• Treatment: Splenectomy (curative)

G6PD Deficiency

• Defect: G6PD enzyme deficiency → inadequate NADPH → RBCs unable to detoxify oxidative stress → Heinz body formation
• Inheritance: X-linked recessive (males affected)
• Triggers: Infections, oxidant drugs (primaquine, dapsone), fava beans
• Smear: Heinz bodies, bite cells (after spleen removes Heinz bodies)
• Type: Episodic intravascular hemolysis

Sickle Cell Disease

• Defect: HbS - point mutation (Glu→Val at position 6 of β-globin)
• Mechanism: HbS polymerizes under low O2 → sickling → vaso-occlusion + hemolysis
• Triggers: Hypoxia, infection, dehydration, acidosis
• Complications: Vaso-occlusive crises (bone pain, stroke, priapism), splenic infarction (autosplenectomy), acute chest syndrome, aplastic crisis (Parvovirus B19)
• Diagnosis: Hb electrophoresis - HbSS pattern
• Peripheral smear: Sickle cells, target cells, Howell-Jolly bodies (asplenia)
• Treatment: Hydroxyurea (↑HbF), bone marrow transplant

Autoimmune Hemolytic Anemia (AIHA)

• Mechanism: Antibodies against RBC antigens → phagocytosis (extravascular) or complement lysis (intravascular)
• Types:
  • Warm AIHA (IgG): Idiopathic, SLE, CLL, drugs (methyldopa). Extravascular.
  • Cold AIHA (IgM): Post-Mycoplasma, post-EBV. Intravascular on warming.
• Diagnosis: Direct Coombs test (DAT) - positive (detects antibody/complement on RBC surface)
• Treatment: Corticosteroids (warm); Avoid cold exposure (cold); Rituximab, splenectomy

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4. APLASTIC ANEMIA

Definition

Etiology

Pathogenesis

1. Immune-mediated (most common): Drugs/viruses alter stem cell antigens → activated Th1 cells → cytokines that suppress hematopoietic progenitors. (Responds to immunosuppressive therapy in 60-70%)
2. Intrinsic stem cell defect: Telomerase mutations → premature stem cell senescence

Clinical Features

• Insidious onset weakness, pallor, dyspnea (from anemia)
• Petechiae, ecchymoses (from thrombocytopenia)
• Serious infections (from neutropenia)
• NO splenomegaly (if present, suspect another diagnosis)

Lab Findings

Diagnosis

• Bone marrow biopsy showing hypocellular/aplastic marrow with fatty replacement is confirmatory.

Treatment

1. Bone marrow (stem cell) transplantation - treatment of choice in patients < 40 years
2. Immunosuppression - Anti-thymocyte globulin (ATG) + Cyclosporine (for patients not eligible for transplant)
3. Supportive: RBC/platelet transfusions, growth factors (G-CSF), antibiotics
4. Eltrombopag (TPO receptor agonist) - for refractory cases
5. Withdraw offending drug (if drug-induced)

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ANEMIA OF CHRONIC DISEASE (ACD)

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HIGH-YIELD EXAM POINTS SUMMARY

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APPROACH TO A PATIENT WITH ANEMIA (Exam Viva)

1. History: Diet, blood loss (GI, menstrual), drugs, family history, symptoms
2. Examination: Pallor, jaundice, splenomegaly, lymphadenopathy, koilonychia
3. First investigation: CBC + peripheral blood smear
4. Classify by MCV:
   • Microcytic → check serum iron, TIBC, ferritin (IDA vs ACD vs Thalassemia)
   • Macrocytic → check B12, folate, peripheral smear
   • Normocytic → check reticulocyte count
     • High reticulocytes → hemolytic anemia (Coombs, osmotic fragility, Hb electrophoresis)
     • Low reticulocytes → aplastic anemia / bone marrow failure (bone marrow biopsy)

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