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🩸 ANEMIA - Full Clinical Case Presentation

Medicine | MBBS Level

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PART 1 - OVERVIEW & DEFINITION

• Males: Hb < 13.5 g/dL
• Females: Hb < 12.0 g/dL
• Pregnant women: Hb < 11.0 g/dL

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PART 2 - CLASSIFICATION

A. By Red Cell Size (MCV-Based - Wintrobe's Classification)

B. By Mechanism (Pathophysiologic Classification)

C. By Reticulocyte Count (Key Clinical Tool)

• Elevated reticulocytes → Hemolysis OR blood loss (marrow is responding)
• Low reticulocytes → Decreased production (marrow failure)

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PART 3 - CLINICAL FEATURES (Common to All Anemias)

• Fatigue, easy fatigability
• Dyspnea on exertion
• Palpitations
• Headache, dizziness
• Reduced exercise tolerance

• Pallor (conjunctiva, palms, nail beds)
• Tachycardia
• Flow murmur (ejection systolic, best heard at pulmonary area)
• In severe cases: cardiac failure, angina

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CASE 1 - IRON DEFICIENCY ANEMIA

Clinical Vignette

A 26-year-old woman presents with 3 months of progressive fatigue, breathlessness on climbing stairs, and pica (craving for ice and chalk). She has heavy menstrual periods (soaking >5 pads/day). On exam: pallor of conjunctiva and palms, angular cheilitis, smooth tongue (atrophic glossitis). No splenomegaly.

Investigation Results

Peripheral Blood Smear

Pathophysiology (Robbins)

1. Cause: Chronic blood loss (menorrhagia) → depletes storage iron (ferritin) → depletes transport iron → hemoglobin synthesis fails
2. Normal diet: 10-20 mg/day; absorb 1-2 mg; women need 7-20 mg/day
3. Heme iron (from meat) absorbed 20% vs non-heme iron only 1-2%
4. Hepcidin falls in iron deficiency → attempts to maximize absorption
5. Bone marrow: erythroid hyperplasia with absent iron stores (Prussian blue stain negative)

Treatment

• Oral ferrous sulfate: 150-200 mg elemental iron/day in divided doses (fasting or with Vit C)
• Reticulocytosis begins in 5-7 days
• Full correction takes 4-6 weeks; continue for 3 months to replenish stores
• Treat the cause (manage menorrhagia)

Examination Questions

Serum ferritin - it directly reflects iron stores. Values < 12 µg/L are diagnostic.

The liver produces more transferrin when iron is deficient to capture any available iron. More "empty" transferrin = elevated TIBC.

Iron deficiency, Thalassemia, Anemia of chronic disease/inflammation, Sideroblastic anemia (mnemonic: TAILS - Thalassemia, Anemia of chronic disease, Iron deficiency, Lead poisoning, Sideroblastic)

Triad of: microcytic hypochromic anemia + atrophic glossitis + esophageal webs. Associated with long-standing severe iron deficiency. Risk factor for postcricoid carcinoma.

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CASE 2 - MEGALOBLASTIC ANEMIA (Vitamin B12 Deficiency)

Clinical Vignette

A 55-year-old vegetarian man presents with fatigue, sore tongue, and tingling/numbness in both feet and hands (glove-and-stocking pattern). He had a gastrectomy 10 years ago. On exam: pallor, mild jaundice (lemon-yellow tinge), smooth beefy red tongue, loss of vibration sense and proprioception in lower limbs bilaterally.

Investigation Results

Morphology (Robbins)

• Peripheral blood: macro-ovalocytes (large oval RBCs without central pallor), hypersegmented neutrophils (5+ lobes - pathognomonic)
• Bone marrow: hypercellular with megaloblasts (nuclear-cytoplasmic asynchrony - cytoplasm matures but nucleus remains immature)
• Giant metamyelocytes and band forms

Pathophysiology

1. B12 required for: thymidine synthesis (DNA) + conversion of methylmalonyl CoA → succinyl CoA (myelin)
2. Intrinsic factor secreted by gastric parietal cells - required for B12 absorption in terminal ileum
3. Gastrectomy → loss of parietal cells → no IF → no B12 absorption (Pernicious anemia if autoimmune)
4. DNA synthesis impaired → ineffective erythropoiesis → pancytopenia + intramedullary hemolysis (elevated LDH and indirect bilirubin)
5. Subacute combined degeneration of spinal cord: B12 deficiency causes demyelination of posterior columns (vibration/proprioception) + lateral corticospinal tracts (UMN signs)

Treatment

• IM Cyanocobalamin/Hydroxocobalamin: 1000 µg daily × 7 days → weekly × 4 → monthly (lifelong)
• Oral B12 1000 µg/day (for dietary deficiency)
• Important: Must rule out B12 deficiency before giving folate alone (folate can correct anemia but WILL NOT prevent/may worsen neurological damage)

Examination Questions

Hypersegmented neutrophils (≥5 lobes in >5% of neutrophils, or any neutrophil with ≥6 lobes) AND macro-ovalocytes.

Neurological features (subacute combined degeneration) occur only in B12 deficiency. Check serum B12, folate, and methylmalonic acid (elevated in B12 deficiency only).

In megaloblasts, DNA synthesis is impaired so the nucleus remains large and immature while the cytoplasm continues to mature normally (accumulates hemoglobin). The nucleus appears "young" for the age of the cell.

Ineffective erythropoiesis leads to intramedullary hemolysis (destruction of megaloblasts in the bone marrow before they enter circulation), releasing bilirubin → elevated indirect bilirubin and LDH.

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CASE 3 - HEMOLYTIC ANEMIA

Clinical Vignette

A 19-year-old male student develops sudden onset of dark urine, jaundice, and pallor 2 days after taking primaquine for malaria prophylaxis. His urine appears dark brown ("Coca-Cola colored"). No splenomegaly. His maternal uncle had a similar episode.

Investigation Results

Pathophysiology (Robbins)

• X-linked recessive (more common in males)
• G6PD needed to regenerate glutathione (protects RBCs from oxidative damage)
• Oxidant stress (primaquine, dapsone, fava beans, infections) → hemoglobin oxidation → Heinz bodies → RBC destruction

Treatment

• Withdraw precipitating drug
• Transfusion if severe
• Folic acid supplementation
• Avoid triggers (oxidant drugs, fava beans)

Examination Questions

Intravascular: hemoglobinuria, hemoglobinemia, very low haptoglobin. Extravascular: splenomegaly, jaundice (no free hemoglobin in urine).

Elevated reticulocytes, elevated indirect bilirubin, elevated LDH, low haptoglobin, +/- peripheral smear evidence of hemolysis.

Direct Coombs (DAT) detects antibodies/complement on RBC surface - positive in autoimmune hemolytic anemia (AIHA), hemolytic transfusion reactions, drug-induced hemolysis.

Intrinsic (intracorpuscular): G6PD deficiency, pyruvate kinase deficiency, hereditary spherocytosis, sickle cell disease, thalassemia, PNH. Extrinsic (extracorpuscular): AIHA, malaria, microangiopathic HA (TTP, HUS, DIC), mechanical valves.

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CASE 4 - APLASTIC ANEMIA

Clinical Vignette

A 22-year-old male presents with 6 weeks of progressive fatigue, spontaneous bruising over his limbs, recurrent oral ulcers, and a 5-day history of high fever not responding to antibiotics. He took carbamazepine for 3 months. On exam: pallor, scattered petechiae and ecchymoses, no splenomegaly, no lymphadenopathy.

Investigation Results

Pathophysiology (Robbins & Kumar)

1. Multipotent myeloid stem cells are suppressed → bone marrow failure → pancytopenia
2. Immune-mediated (most common): Activated T cells produce cytokines → suppress hematopoietic progenitors. Evidence: 60-70% respond to immunosuppression
3. Intrinsic stem cell defect: Telomerase defects in 5-10%; shortened telomeres → premature stem cell senescence
4. Causes: Idiopathic (most common), drugs (carbamazepine, chloramphenicol, NSAIDs, gold), viruses (hepatitis, EBV, CMV, parvovirus B19), radiation, chemicals (benzene)
5. No splenomegaly - if spleen is enlarged, consider another diagnosis

Severity Classification (Camitta Criteria)

Treatment

• Age < 40, HLA-matched sibling: Allogeneic stem cell transplantation (curative)
• No matched donor / age > 40: Antithymocyte globulin (ATG) + Cyclosporin + Eltrombopag (immunosuppression)
• Supportive: packed RBC transfusion, platelet transfusion, antibiotics
• Minimize transfusions in transplant candidates (allosensitization → graft failure)

Examination Questions

Bone marrow biopsy - shows hypocellular marrow with >90% fat cells and absent/markedly reduced hematopoietic elements.

Anaemia (pallor, fatigue) + thrombocytopenia (petechiae, bruising, bleeding) + neutropenia (recurrent infections, fever). This is pancytopenia.

Both cause pancytopenia. Leukemia: hepatosplenomegaly, lymphadenopathy, circulating blasts on smear, hypercellular marrow with blasts. Aplastic anemia: no organomegaly, no blasts, hypocellular fatty marrow.

Transfusions sensitize the patient to HLA antigens (allosensitization), greatly increasing the risk of graft rejection after stem cell transplantation.

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PART 4 - COMPARISON TABLE: THE BIG 4 ANEMIAS

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PART 5 - HIGH-YIELD MNEMONICS

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PART 6 - EXAM SPOTTERS

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CLINICAL CASE PROFORMA

Department of Medicine | MBBS Undergraduate Teaching

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PROFORMA 1 - IRON DEFICIENCY ANEMIA

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PATIENT IDENTIFICATION

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CHIEF COMPLAINTS

1. Fatigue and weakness - 3 months
2. Breathlessness on exertion (climbing stairs) - 2 months
3. Craving for ice and chalk (pica) - 1 month
4. Excessive menstrual bleeding - 6 months

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HISTORY OF PRESENT ILLNESS

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PAST HISTORY

• Similar illness: No prior episodes
• Medical: No known DM, HTN, thyroid disease
• Surgical: No prior operations
• Drug history: No NSAIDs, antacids, tetracyclines
• Allergy: Nil known

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OBSTETRIC & MENSTRUAL HISTORY

• LMP: ___________
• Cycle: Irregular, heavy (menorrhagia), 8-10 days duration
• Married × 4 years; G2P2L2; last delivery 18 months ago (normal vaginal delivery)
• No current pregnancy

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DIETARY HISTORY

• Predominantly vegetarian; rarely eats meat
• Low fruit and vegetable intake
• Drinks 3-4 cups of tea daily (tannins reduce iron absorption)

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FAMILY HISTORY

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PERSONAL HISTORY

• Diet: Vegetarian, inadequate
• Sleep: Reduced (fatigue)
• Bowel/Bladder: Normal
• Appetite: Decreased
• Addiction: Nil

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GENERAL PHYSICAL EXAMINATION

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SYSTEMIC EXAMINATION

• Apex beat: 5th ICS, MCL (shifted - hyperdynamic)
• S1, S2 heard; ejection systolic flow murmur at pulmonary area (grade 2/6)
• No diastolic murmur

• Soft, non-tender
• No hepatomegaly; No splenomegaly
• No ascites

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INVESTIGATIONS

• Hypochromic, microcytic RBCs
• Large zone of central pallor (>1/3 cell diameter)
• Pencil cells (elongated elliptocytes)
• Anisocytosis and poikilocytosis
• No abnormal WBCs or platelets

• Stool for occult blood: Negative
• USG Pelvis: Bulky uterus (fibroid)
• Serum folate/B12: Normal
• RBS: Normal

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DIAGNOSIS

1. Thalassemia trait (but normal Hb electrophoresis + positive family history expected)
2. Anemia of chronic disease (but TIBC would be low, not high)
3. Sideroblastic anemia (rare; ring sideroblasts on marrow)

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TREATMENT

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PROGNOSIS

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PROFORMA 2 - MEGALOBLASTIC ANEMIA (B12 DEFICIENCY / PERNICIOUS ANEMIA)

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PATIENT IDENTIFICATION

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CHIEF COMPLAINTS

1. Fatigue, weakness - 4 months
2. Tingling and numbness in both hands and feet - 2 months
3. Difficulty walking, unsteadiness - 6 weeks
4. Sore, burning tongue - 1 month
5. Mild yellowish discoloration of skin - 1 month

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HISTORY OF PRESENT ILLNESS

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PAST HISTORY

• Subtotal gastrectomy 10 years ago (peptic ulcer)
• No DM, HTN, thyroid disease
• No long-term medications
• No alcohol or smoking

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GENERAL PHYSICAL EXAMINATION

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SYSTEMIC EXAMINATION

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INVESTIGATIONS

• Macro-ovalocytes (large oval RBCs without central pallor)
• Hypersegmented neutrophils (>5 lobes; some with 6-7 lobes)
• Anisocytosis, poikilocytosis
• Thrombocytopenia (large platelets)

• Hypercellular
• Megaloblasts (nuclear-cytoplasmic asynchrony)
• Giant metamyelocytes and band forms

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DIAGNOSIS

1. Folate deficiency (no neurological features; folate normal here)
2. Myelodysplastic syndrome (but normal morphology of blasts expected; rule out with marrow)
3. Hypothyroid macrocytosis (check TFTs)

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TREATMENT

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PROGNOSIS

• Hematological response begins within 1 week
• Neurological recovery: variable; depends on duration (may not fully reverse if > 6 months)
• Lifelong B12 replacement required

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PROFORMA 3 - HEMOLYTIC ANEMIA (G6PD DEFICIENCY)

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PATIENT IDENTIFICATION

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CHIEF COMPLAINTS

1. Dark brown urine (hemoglobinuria) - 2 days
2. Yellowish discoloration of eyes - 2 days
3. Fatigue and pallor - 2 days
4. Drug intake: Primaquine started 3 days ago

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HISTORY OF PRESENT ILLNESS

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PAST HISTORY

• No prior anemia or transfusion
• No DM, thyroid disease
• No chronic medications
• Family history: Maternal uncle - similar episode with sulfa drug

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GENERAL PHYSICAL EXAMINATION

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SYSTEMIC EXAMINATION

• Liver: Not palpable
• Spleen: Not palpable (intravascular hemolysis - spleen not involved)
• No ascites

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INVESTIGATIONS

• Color: Dark brown
• Hemoglobin: Positive (hemoglobinuria)
• RBCs: Absent (distinguishes from hematuria)
• Hemosiderin: Present

• "Bite cells" (eccentrocytes) - RBCs with Hb pushed to one side
• Blister cells
• Polychromasia (reticulocytes)
• Heinz bodies visible on supravital stain (brilliant cresyl blue)
• No spherocytes; No sickle cells

• G6PD quantitative assay: Severely deficient (< 10% of normal)
• Note: Test should be repeated 6-8 weeks after acute episode (reticulocytes have normal G6PD activity - may give falsely normal result in acute phase)

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DIAGNOSIS

1. Autoimmune hemolytic anemia (Coombs negative here - excluded)
2. Paroxysmal nocturnal hemoglobinuria - PNH (flow cytometry for CD55/CD59 - negative here)
3. Sickle cell crisis (no sickle cells on smear; Hb electrophoresis normal)
4. Glucose-6-phosphate isomerase deficiency (very rare)

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PATHOPHYSIOLOGY (Brief)

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TREATMENT

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PROGNOSIS

• Acute episode is self-limiting (once offending drug withdrawn)
• Hb recovers in 3-4 weeks
• Future episodes preventable by avoiding oxidant triggers
• No chronic hemolysis in the Mediterranean/African G6PD variants (WHO Class II/III)

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PROFORMA 4 - APLASTIC ANEMIA

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PATIENT IDENTIFICATION

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CHIEF COMPLAINTS

1. Progressive fatigue, pallor - 6 weeks
2. Spontaneous bruising over limbs - 4 weeks
3. Recurrent mouth ulcers - 3 weeks
4. High-grade fever, not responding to antibiotics - 5 days
5. Gum bleeding on brushing - 2 weeks

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HISTORY OF PRESENT ILLNESS

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PAST HISTORY

• Epilepsy (idiopathic, generalized tonic-clonic)
• No prior blood disorders or transfusions
• No DM, HTN, infections (hepatitis, HIV negative on testing)
• No exposure to radiation or industrial chemicals

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FAMILY HISTORY

• No similar illness in family
• No consanguinity
• No known hematological disorders

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GENERAL PHYSICAL EXAMINATION

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SYSTEMIC EXAMINATION

• Liver: Not palpable
• Spleen: Not palpable ← CRITICAL FINDING
• No ascites, no lymphadenopathy in abdomen

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INVESTIGATIONS

• Pancytopenia
• Red cells: Normochromic, normocytic
• No blast cells (rules out leukemia)
• No abnormal lymphocytes
• No dysplastic changes

• Biopsy: Hypocellular marrow with >90% fat cells
• Almost complete absence of hematopoietic elements
• No blasts, no fibrosis, no granulomas
• Confirms aplastic anemia

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SEVERITY CLASSIFICATION (Camitta Criteria)

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DIAGNOSIS

1. Acute leukemia (pancytopenia + blasts - ruled out: no blasts, hypocellular marrow)
2. Myelodysplastic syndrome (dysplasia on smear - ruled out: no dysplasia, normal karyotype)
3. Hypersplenism (no splenomegaly here)
4. Megaloblastic anemia with pancytopenia (MCV normal, B12/folate normal)
5. PNH (flow cytometry negative)

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TREATMENT

Very Severe Aplastic Anemia
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   Age 22 years
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   HLA typing
   (sibling first)
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   |              |
Matched sibling   No matched sibling
present?          available?
   |                    |
Allogeneic BMT    ATG + Cyclosporin
(curative, 70-80% + Eltrombopag
overall survival) (immunosuppression)

• Minimize transfusions (allosensitization risk)
• Use irradiated, leukodepleted blood products only
• Myeloablative conditioning: Cyclophosphamide + ATG

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PROGNOSIS

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FOLLOW-UP PLAN

• Daily CBC till stabilization
• Repeat bone marrow biopsy at 3 months (post-treatment)
• Monitor for PNH clone development (10% of aplastic anemia evolve to PNH)
• Long-term watch for MDS/AML transformation (especially post-immunosuppression)

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COMPARISON SUMMARY (All 4 Cases)

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HISTORY OF PRESENT ILLNESS

Case 1 - Iron Deficiency Anemia | Mrs. Sunita Devi, 26F

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ONSET AND PROGRESSION OF MAIN COMPLAINTS

1. Fatigue and Weakness (3 months)

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2. Breathlessness on Exertion (2 months)

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3. Pica - Craving for Ice and Chalk (1 month)

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4. Heavy Menstrual Bleeding - Menorrhagia (6 months)

• Duration of bleeding has increased to 8-10 days per cycle
• She soaks more than 5 fully saturated pads per day during peak flow (days 2-4)
• She has passed clots on multiple occasions (clots larger than a 10-rupee coin)
• She experiences dysmenorrhoea (cramping lower abdominal pain during periods), which is new for her
• She has had inter-menstrual spotting on 2-3 occasions
• She has not consulted a gynecologist despite the severity

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5. Associated Symptoms (1-2 months)

• Hairfall: Excessive hair loss on combing and washing, forming clumps. Not patchy. Present for 6 weeks.
• Soreness and burning of tongue (glossitis): Present for 4 weeks. The tongue feels raw and burning, especially while eating spicy food. She avoids spicy foods due to this.
• Cracks at corners of mouth (angular cheilitis): Painful fissures at both corners of the mouth for 3 weeks. Worsen during cold weather.
• Brittle, spoon-shaped nails (koilonychia): Noticed for 2 months. Her nails break easily and she noticed they appear "hollowed out."
• Palpitations: Intermittent awareness of heartbeats, especially at rest and at night, for 3 weeks. No associated chest pain, syncope, or dizziness.
• Dizziness and mild headache: Intermittent frontal headache and lightheadedness on standing up quickly (postural dizziness). Present for 2 months.

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RELEVANT NEGATIVE HISTORY (Pertinent Negatives)

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TREATMENT HISTORY

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DIETARY HISTORY (Integrated in HPI)

• Strict vegetarian (no meat, fish, or eggs)
• Predominantly wheat/rice-based diet with lentils (dal) and leafy vegetables 2-3 times per week
• Drinks 4-5 cups of tea per day, including with meals (tea contains tannins that inhibit iron absorption by up to 60%)
• Rarely consumes citrus fruits or Vitamin C-rich foods (which would enhance iron absorption)
• This dietary pattern means she consumes predominantly non-heme iron (1-2% absorption) with dietary inhibitors, providing far less than the 7-20 mg/day required for a premenopausal woman

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COURSE OF ILLNESS

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SUMMARY OF HPI

Mrs. Sunita Devi, 26F, vegetarian homemaker, presents with a 6-month history of progressive iron depletion due to menorrhagia (likely secondary to uterine fibroid on USG), superimposed on an inadequate dietary iron intake. This has resulted in a 3-month history of symptomatic moderate anemia (fatigue, exertional dyspnoea, palpitations, dizziness), progressive tissue iron depletion (koilonychia, angular cheilitis, glossitis, alopecia), and pica (pagophagia - craving for ice). There are no features of hemolysis, bleeding diathesis, malabsorption, neurological involvement, or alternate cause of anemia.

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HISTORY OF PRESENT ILLNESS

Iron Deficiency Anemia | Male Patient

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CHIEF COMPLAINTS (Recap)

1. Progressive fatigue and weakness - 5 months
2. Breathlessness on exertion - 3 months
3. Black, tarry stools (melena) - intermittent, 5 months
4. Loss of appetite and 4 kg weight loss - 3 months
5. Burning epigastric pain - 6 months

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ONSET AND PROGRESSION

1. Epigastric Pain (6 months) - The Underlying Cause

• Onset: Gradual, insidious
• Character: Burning, gnawing
• Location: Epigastrium, occasionally radiating to the back
• Timing: Occurs 1-2 hours after meals and also wakes him from sleep at night (early morning hours)
• Relieving factors: Partially relieved by eating food and by antacids (which he has been self-medicating with for 4 months)
• Aggravating factors: Worsened by spicy food, alcohol (he consumes alcohol approximately 4-5 days per week, local liquor)
• Severity: Moderate; does not prevent him from working

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2. Melena - Black Tarry Stools (5 months)

• The stool is jet black, tarry, and has a distinctly foul odor (consistent with altered blood - rules out simple dark stool from iron/bismuth)
• He has passed no fresh red blood per rectum (no hematochezia)
• No hematemesis (vomiting of blood)
• No history of frank rectal bleeding, mucus, or altered bowel habit (no alternating constipation-diarrhea)
• He estimates passing tarry stools approximately 8-10 times over the past 5 months

Clinical significance: In an adult male, GI blood loss causing iron deficiency must be evaluated for a structural lesion (peptic ulcer, gastric carcinoma, colorectal cancer) until proven otherwise. This is a red flag requiring urgent endoscopy.

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3. Fatigue and Weakness (5 months)

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4. Breathlessness on Exertion (3 months)

• Gradual in onset, progressive
• Exertional only - no breathlessness at rest
• No orthopnoea, no paroxysmal nocturnal dyspnoea
• No ankle swelling (no cardiac failure)
• No prior history of cardiac or pulmonary disease
• No smoking history

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5. Loss of Appetite and Weight Loss (3 months)

Clinical significance: Significant weight loss (>5% body weight in 3 months) combined with epigastric pain, melena, and iron deficiency anemia in a middle-aged male raises the concern for gastric malignancy until proven otherwise. This is a mandatory red flag.

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6. Additional Symptoms of Iron Deficiency (Tissue Depletion)

• Pica: The patient admits to craving and chewing raw rice and mud (geophagia) for the past 2 months. He discloses this reluctantly on direct questioning.
• Hairfall: Increased hair loss on combing, noted for 6 weeks
• Brittle nails: Nails break easily; wife noticed they appear concave (koilonychia) for 4-6 weeks
• Soreness of tongue: Tongue feels raw and smooth; mild burning with spicy foods for 4 weeks (atrophic glossitis)
• Angular cheilitis: Painful cracks at corners of mouth for 3 weeks
• Dizziness on standing: Postural dizziness (lightheadedness) when rising from squatting or lying position, for 4-6 weeks
• Palpitations: Intermittent awareness of fast heartbeat, particularly at rest at night, for 3 weeks. No syncope, no chest pain.

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ALCOHOL HISTORY (Relevant to Cause)

• Chronic alcohol use causes gastric mucosal erosions and peptic ulceration, contributing to GI blood loss
• Alcohol interferes with folate absorption (may contribute to combined deficiency)
• Alcohol can cause round macrocytosis independent of anemia, potentially masking the microcytosis of IDA on MCV

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RELEVANT NEGATIVE HISTORY (Pertinent Negatives)

Note on hookworm: This patient works barefoot on farm soil. Hookworm (Ancylostoma duodenale) infestation causes chronic intestinal blood loss and is an important cause of iron deficiency anemia in rural agricultural laborers in India. Stool examination for ova and parasites is essential.

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TREATMENT HISTORY

• Self-medicating with antacids (Tab ranitidine, OTC) for 4 months - no prescription
• No prior iron supplementation
• No prior endoscopy or investigation for GI symptoms
• No prior blood transfusions
• No herbal/traditional medicines

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DIETARY HISTORY (Integrated)

• Non-vegetarian but meat consumed only 1-2 times per week (limited income)
• Main diet: wheat rotis, dal, seasonal vegetables
• Eats very few fruits; no citrus
• Drinks 4-5 cups of tea daily including with meals (tannins inhibit non-heme iron absorption)
• Chronic alcohol use as above
• Despite being non-vegetarian, his dietary iron intake is insufficient to compensate for ongoing GI blood loss

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OCCUPATIONAL HISTORY

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COURSE OF ILLNESS

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SUMMARY OF HPI

Mr. Rajesh Verma, 52M, a farmer with chronic alcoholism, presents with a 5-month history of iron deficiency anemia secondary to chronic gastrointestinal blood loss, manifesting as progressive fatigue, exertional dyspnoea, and features of tissue iron depletion (koilonychia, angular cheilitis, atrophic glossitis, pica). The likely source of blood loss is a peptic ulcer/gastric lesion given the 6-month history of burning epigastric pain relieved by food and antacids, intermittent melena, significant weight loss (4 kg/3 months), and risk factors of chronic alcohol use. Gastric malignancy must be actively excluded by urgent upper GI endoscopy. Hookworm infestation as an additional contributing cause requires exclusion by stool examination. There are no features of hemolysis, neurological involvement, or alternate hematological diagnosis.

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KEY CLINICAL TEACHING POINTS FOR THIS CASE

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GENERAL QUESTIONS ASKED IN HISTORY OF PRESENT ILLNESS

Anemia - Any Case | MBBS Bedside Clerking Guide

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WHY WE ASK A STRUCTURED HPI IN ANEMIA

1. How severe is the anemia? (symptoms of oxygen deprivation)
2. What type is it? (clues from associated symptoms)
3. What is the cause? (bleeding, destruction, decreased production)

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SECTION 1 - QUESTIONS ABOUT THE ANEMIA SYMPTOMS THEMSELVES

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A. Fatigue / Weakness

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B. Breathlessness

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C. Palpitations

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D. Dizziness / Headache

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SECTION 2 - QUESTIONS TO FIND THE CAUSE OF ANEMIA

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A. Questions for Blood Loss

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B. Questions for Hemolysis (Destruction)

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C. Questions for Decreased Production

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SECTION 3 - SPECIFIC SYMPTOM QUESTIONS BY ANEMIA TYPE

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For Iron Deficiency - Ask These Specifically

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For Megaloblastic Anemia (B12/Folate) - Ask These Specifically

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For Hemolytic Anemia - Ask These Specifically

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For Aplastic Anemia - Ask These Specifically

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SECTION 4 - GENERAL QUESTIONS ASKED IN EVERY ANEMIA HPI

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SECTION 5 - PERTINENT NEGATIVES TO ALWAYS ASK AND DOCUMENT

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QUICK SUMMARY TABLE

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CAUSES OF ANEMIA

Acute vs Chronic Classification

MBBS Medicine | Complete Reference

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PART 1 - ACUTE CAUSES OF ANEMIA

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A. ACUTE BLOOD LOSS (Hemorrhagic Anemia)

• Normocytic, normochromic initially
• Reticulocytosis appears after 5-7 days
• Hb may be normal in first few hours (hemodilution not yet complete)
• Tachycardia, hypotension, cold peripheries (shock features)

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B. ACUTE HEMOLYSIS

• Sudden pallor + jaundice + dark urine (hemoglobinuria)
• Normocytic (or slightly macrocytic due to reticulocytosis)
• Reticulocytes elevated within 24-48 hours
• LDH very high, haptoglobin absent, indirect bilirubin elevated
• May cause acute kidney injury (hemoglobin precipitates in tubules)

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C. ACUTE BONE MARROW SUPPRESSION

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PART 2 - CHRONIC CAUSES OF ANEMIA

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A. CHRONIC BLOOD LOSS → IRON DEFICIENCY

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B. NUTRITIONAL DEFICIENCY ANEMIAS (Chronic)

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C. CHRONIC HEMOLYTIC ANEMIAS

i. Intrinsic (Intracorpuscular) Defects

ii. Extrinsic (Extracorpuscular) Defects

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D. CHRONIC DECREASED PRODUCTION ANEMIAS

i. Anemia of Chronic Disease / Inflammation (ACD)

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ii. Renal Anemia (Anemia of CKD)

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iii. Endocrine Anemias

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iv. Bone Marrow Failure / Aplastic Anemia

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v. Bone Marrow Infiltration (Myelophthisic Anemia)

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vi. Pure Red Cell Aplasia (PRCA)

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vii. Dyserythropoietic / Ineffective Erythropoiesis

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SUMMARY TABLE - ACUTE vs CHRONIC

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MNEMONIC - CAUSES OF CHRONIC ANEMIA

• B - B12 / Folate deficiency (megaloblastic)
• I - Iron deficiency (chronic blood loss / dietary)
• N - Nutritional (protein, copper)
• D - Disease (anemia of chronic disease / inflammation)
• M - Marrow failure (aplastic anemia)
• A - Anemia of CKD (EPO deficiency)
• R - RBC destruction (chronic hemolysis - hereditary spherocytosis, sickle cell, thalassemia)
• R - Replacement of marrow (myelophthisic anemia - metastasis, leukemia)

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PHYSICAL EXAMINATION IN ANEMIA

Complete Bedside Guide | MBBS Medicine

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APPROACH TO EXAMINATION

1. Confirm the presence and severity of anemia
2. Find clues to the TYPE and CAUSE of anemia

General Physical Examination → Vital Signs → Systemic Examination

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PART 1 - GENERAL PHYSICAL EXAMINATION

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1. BUILT AND NOURISHMENT

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2. PALLOR ← MOST IMPORTANT SIGN

Exam Tip: Conjunctival pallor is the most reliable sign. Palmar pallor has poor sensitivity. Always grade and document.

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3. ICTERUS (JAUNDICE)

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4. CYANOSIS

• Absent in pure anemia (anemia = low Hb, not desaturated Hb)
• If present → suggests concomitant respiratory/cardiac disease
• Important: Severe anemia can MASK cyanosis (not enough Hb to appear blue even if desaturated)

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5. CLUBBING

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6. LYMPHADENOPATHY

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7. EDEMA

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8. SPECIFIC SIGNS OF IRON DEFICIENCY (Tissue Depletion Signs)

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9. SPECIFIC SIGNS OF MEGALOBLASTIC ANEMIA

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10. SPECIFIC SIGNS OF HEMOLYTIC ANEMIA

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11. SPECIFIC SIGNS OF APLASTIC ANEMIA

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PART 2 - VITAL SIGNS

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PULSE

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BLOOD PRESSURE

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RESPIRATORY RATE

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TEMPERATURE

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SpO2

• Usually normal in anemia (oxygen saturation measures % saturation, not total O2 content)
• May be low if concomitant respiratory/cardiac disease
• Important teaching point: SpO2 can be falsely NORMAL in severe anemia - patient is hypoxic in terms of O2 delivery but SpO2 reads 98-99%

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PART 3 - SYSTEMIC EXAMINATION

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A. CARDIOVASCULAR EXAMINATION

Inspection

• Visible apex beat in severe anemia (hyperdynamic circulation)

Palpation

Auscultation

Key Teaching: The flow murmur of anemia is systolic, short, soft (≤2/6), and disappears when anemia is treated. It has no diastolic component and no radiation. If diastolic murmur present → organic valvular disease.

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B. RESPIRATORY EXAMINATION

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C. ABDOMINAL EXAMINATION

SPLEEN - Most Important Abdominal Finding in Anemia

How to Examine the Spleen:

1. Patient supine, knees flexed
2. Start palpation from right iliac fossa (not left) - palpate diagonally toward left hypochondrium
3. Ask patient to take deep breath - feel for splenic notch moving toward you
4. If not palpable supine → examine in right lateral decubitus position (brings spleen forward)
5. Percussion (Traube's space): Normally resonant (gastric air bubble). Dullness = splenomegaly
6. Confirm with percussion: Dull in Traube's space

Spleen Size Classification:

Splenomegaly in Anemia:

Key Rule: Aplastic anemia does NOT cause splenomegaly. If spleen is palpable, reconsider the diagnosis.

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LIVER

Remember: Hepatosplenomegaly with anemia in a young patient → think thalassemia or leukemia. In an older patient → think myelofibrosis, lymphoma, or carcinoma.

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OTHER ABDOMINAL FINDINGS

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D. NEUROLOGICAL EXAMINATION

Posterior Column (Dorsal Column) Signs - B12 Deficiency

Lateral Corticospinal Tract Signs - B12 Deficiency

Combined Posterior + Lateral Column = Subacute Combined Degeneration of Spinal Cord (SACD)

Pattern: Loss of vibration + proprioception (posterior column) + UMN signs (lateral column) = pathognomonic of B12 deficiency

Additional Neurological Findings in Anemia

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E. MUSCULOSKELETAL / BONE EXAMINATION

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PART 4 - EXAMINATION FINDINGS BY ANEMIA TYPE (Quick Reference)

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PART 5 - EXAMINATION SUMMARY TEMPLATE

(For writing in case notes)

GENERAL PHYSICAL EXAMINATION:
Built and nourishment: ___________
Pallor: Present/Absent (Grade: +/++/+++)  
  - Conjunctivae: ___________
  - Palms: ___________
  - Nail beds: ___________
  - Tongue: ___________
Icterus: Present/Absent
Cyanosis: Present/Absent
Clubbing: Present/Absent
Lymphadenopathy: Present/Absent
Edema: Present/Absent
Koilonychia: Present/Absent
Angular cheilitis: Present/Absent
Atrophic glossitis: Present/Absent
Petechiae/Ecchymoses: Present/Absent

VITAL SIGNS:
Pulse: ___/min, regular/irregular, volume: normal/low/high
BP: ___/___ mmHg (Postural drop: Yes/No)
RR: ___/min
Temperature: ___°C
SpO2: ___%

CARDIOVASCULAR:
Apex beat: _____ ICS, _____ (position)
Heart sounds: S1 S2 heard / Flow murmur: Yes/No
Murmur details: ___________

ABDOMEN:
Liver: Palpable/Not palpable (___ cm below costal margin)
Spleen: Palpable/Not palpable (Grade ___, ___ cm below costal margin)
Notch: Present/Absent
Traube's space: Resonant/Dull
Ascites: Present/Absent

CNS:
Vibration sense: Present/Absent at ___________
Proprioception: Present/Absent at ___________
Romberg's test: Positive/Negative
Deep tendon reflexes: Normal/Brisk/Absent
Plantar response: Flexor/Extensor
Fundus: Normal/Retinal hemorrhages

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TREATMENT OF ANEMIA

By Type | Complete MBBS Medicine Reference

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GENERAL PRINCIPLES BEFORE STARTING TREATMENT

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TYPE 1 - IRON DEFICIENCY ANEMIA (IDA)

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STEP 1 - TREAT THE CAUSE

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STEP 2 - IRON SUPPLEMENTATION

Oral Iron (First Line)

• Take with Vitamin C (100-200 mg) - increases absorption 2-3 fold
• Avoid taking with tea, milk, antacids, calcium supplements, tetracyclines

• Constipation (most common)
• Dark/black stools (reassure patient - normal)
• Nausea, epigastric discomfort
• Management: Take after food (reduces GI side effects but also reduces absorption slightly)

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Monitoring Oral Iron Response

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Parenteral Iron (IV/IM) - When to Use

Total iron (mg) = Body weight (kg) × (Target Hb - Actual Hb) g/dL × 2.4 + 500 (for stores)

• Anaphylaxis (rare but life-threatening - keep resuscitation ready)
• Hypotension, flushing (infusion reaction)
• Phlebitis at injection site

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STEP 3 - BLOOD TRANSFUSION

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STEP 4 - ADJUVANTS

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TYPE 2 - MEGALOBLASTIC ANEMIA

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A. VITAMIN B12 DEFICIENCY

Parenteral B12 (Standard Treatment)

• Pernicious anemia / post-gastrectomy = no intrinsic factor = oral B12 not absorbed via normal pathway
• IM bypasses the need for intrinsic factor completely

Oral B12 (High Dose)

Monitoring Response to B12 Treatment

Neurological Response:

• Sensory symptoms often improve first
• Motor and posterior column signs may partially or fully recover
• If no improvement in neurology after 3-6 months → likely permanent damage

Important Precautions

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B. FOLATE DEFICIENCY

• Stop offending drugs (methotrexate - switch if possible; phenytoin - liaise with neurology)
• Alcohol abstinence
• Treat malabsorption

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TYPE 3 - HEMOLYTIC ANEMIA

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A. G6PD DEFICIENCY (Drug/Oxidant-Induced)

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B. AUTOIMMUNE HEMOLYTIC ANEMIA (AIHA)

Warm AIHA (IgG - Most Common)

Cold Agglutinin Disease (IgM)

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C. HEREDITARY SPHEROCYTOSIS

• Pneumococcal vaccine (PCV13 + PPSV23)
• Meningococcal vaccine
• Haemophilus influenzae type B vaccine
• Annual influenza vaccine

• Daily prophylactic penicillin V (250 mg BD) - lifelong or minimum 2-5 years
• Risk of overwhelming post-splenectomy infection (OPSI) - especially encapsulated organisms

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D. SICKLE CELL DISEASE

Chronic Management

Acute Painful Crisis

Curative Treatment

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E. THALASSEMIA

Beta-Thalassemia Major (Cooley's Anemia)

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F. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)

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TYPE 4 - APLASTIC ANEMIA

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TREATMENT ALGORITHM

Confirmed Aplastic Anemia
          |
    Severity Assessment
          |
    ---------------
    |             |
  Severe/        Moderate
  Very Severe     |
    |           Watch and wait
    |           + Supportive
  Age ≤ 40      care
  + Matched      |
  Sibling?       If worsens →
    |            treat as severe
  YES → HSCT
  NO → Immunosuppression

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A. SUPPORTIVE CARE (ALL PATIENTS)

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B. DEFINITIVE TREATMENT

1. Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

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2. Immunosuppressive Therapy (IST)

• Complete response: Hb normal, ANC >1000, plt >100,000
• Partial response: No longer dependent on transfusions
• No response: Consider 2nd course of ATG, HSCT with unrelated donor, or eltrombopag continuation

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3. Eltrombopag (Promacta) - Thrombopoietin Receptor Agonist

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4. Pure Red Cell Aplasia (PRCA)

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TYPE 5 - ANEMIA OF CHRONIC DISEASE (ACD)

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TYPE 6 - ANEMIA OF CKD

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TYPE 7 - MYELOPHTHISIC / MARROW INFILTRATION ANEMIA

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BLOOD TRANSFUSION - GENERAL GUIDELINES

Indications

Types of Blood Products

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SUMMARY TABLE - TREATMENT BY TYPE

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