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IST Internal Assignments - Haematology (2024 Batch) - Answers

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CASE 1

• Microcytic, hypochromic red cells (small RBCs with increased central pallor - pencil/cigar-shaped cells)
• Anisocytosis and poikilocytosis
• Target cells (codocytes)
• Pencil cells (elliptocytes)
• Reduced RBC count

1. Chronic blood loss from blood-streaked stool (likely GI bleeding) leads to iron depletion - the most common cause of IDA
2. Fatigue and anaemia - due to reduced haemoglobin synthesis from lack of iron
3. The peripheral smear shows microcytic hypochromic cells because iron is essential for haem synthesis; without adequate iron, haemoglobin is reduced per cell
4. Intermittent GI bleed is a classic cause of IDA in young adults

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CASE 2

• Macrocytic (large) red blood cells (MCV > 100 fl)
• Oval macrocytes (macro-ovalocytes)
• Hypersegmented neutrophils (5 or more lobes - pathognomonic)
• Anisocytosis and poikilocytosis
• Low RBC count, may show pancytopenia

1. Peripheral neuropathy (tingling/numbness) - B12 deficiency causes subacute combined degeneration of the spinal cord; folate deficiency does NOT cause neuropathy - so B12 deficiency is strongly implicated here
2. Macrocytes - B12/folate is needed for DNA synthesis; deficiency impairs cell division leading to large RBCs (ineffective erythropoiesis)
3. Hypersegmented neutrophils - characteristic of megaloblastic anaemia; neutrophils also undergo impaired maturation
4. Loss of appetite and fatigue are systemic features of B12/folate deficiency

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CASE 3

• Schistocytes (fragmented RBCs) - pathognomonic of MAHA
• Decreased erythrocytes (anaemia)
• Decreased platelets (thrombocytopenia)
• Polychromasia (reticulocytosis)
• Nucleated RBCs may be present

1. Schistocytes - RBCs are physically sheared by fibrin strands in small vessels, producing helmet cells and fragmented RBCs
2. Elevated total bilirubin (19.1 mg/dl) with predominant indirect fraction = intravascular haemolysis (RBC destruction releases unconjugated bilirubin)
3. Dark urine = haemoglobinuria (free haemoglobin from lysed RBCs filtered by kidneys)
4. Elevated WBC = reactive leucocytosis due to haemolytic stress and infection/inflammation
5. Abdominal and back pain = features of haemolysis and microthrombi in visceral vessels

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CASE 4

• Most likely: Sickle Cell Disease (given stroke in a young person + haemolytic markers)

• Sickle-shaped (drepanocytes) red cells
• Target cells
• Polychromasia
• Nucleated RBCs
• Howell-Jolly bodies (due to functional asplenia)

1. Stroke in a young male = vaso-occlusion due to sickled RBCs in cerebral vessels (major complication of SCD)
2. Elevated LDH = marker of intravascular haemolysis (released from lysed RBCs)
3. Elevated bilirubin = unconjugated hyperbilirubinaemia from chronic haemolysis
4. Elevated serum iron and ferritin = iron overload due to chronic haemolytic anaemia (increased iron recycling; may also be from transfusions)
5. In PNH - similar picture but would also show haemoglobinuria and absence of GPI-anchored proteins (CD55/CD59 negative on flow cytometry)

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CASE 5

• Hypergranular promyelocytes with bilobed nuclei
• Auer rods (bundles = "faggot cells") - pathognomonic
• Blast cells (>20% in bone marrow)
• Anaemia, thrombocytopenia
• Reduced normal WBC lineages

1. Gum bleeding + prolonged PT & aPTT = classic DIC (Disseminated Intravascular Coagulation) - APL releases procoagulants from granules of promyelocytes causing DIC; this is the hallmark of APL
2. WBC 50,000/μl = leukaemia (markedly elevated WBC)
3. Hb 7 g/dl = anaemia from bone marrow infiltration
4. Age 40 male + gum bleeding fits APL presentation
5. APL is the AML subtype most commonly associated with DIC and the best prognosis when treated with ATRA (All-Trans Retinoic Acid)

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CASE 6

1. Convulsions + altered sensorium + high fever in an endemic context = classic triad of cerebral malaria
2. Neutrophilia (85%) = reactive leucocytosis (though malaria classically can also show leucopenia; here reactive response to severe infection)
3. Normal Hb (13.5) - early or acute infection; haemolytic anaemia develops later
4. Low BP (90/70 mmHg), SpO2 92%, tachycardia, tachypnoea = sepsis/severe malaria with multi-organ involvement

• Cerebral malaria (P. falciparum) - most likely
• Bacterial meningitis
• Viral encephalitis
• Febrile seizures
• Cerebral abscess
• Typhoid encephalopathy
• Septic encephalopathy

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CASE 7

• Primary: Allergic Asthma with Eosinophilia
• Differential: Löffler's Syndrome / Tropical Pulmonary Eosinophilia (given countryside visit - parasite exposure)

1. Eosinophilia (18%) = hallmark - normal eosinophils <5%; markedly elevated here suggesting allergic or parasitic aetiology
2. Bronchospasm (FEV1 70%, bilateral wheeze) = obstructive airway disease consistent with asthma/allergic response
3. Jelly-like (mucoid) expectoration = thick eosinophil-rich mucus plugs (Curschmann's spirals, Charcot-Leyden crystals)
4. History of countryside visit = exposure to allergens/parasite larvae (Ascaris, hookworm can cause pulmonary eosinophilia - Löffler's syndrome)
5. RDW 15.5 (slightly elevated) suggests some RBC variation

• Allergic conditions (asthma, hay fever, eczema)
• Parasitic infections (Ascaris, hookworm, Toxocara, Strongyloides, filariasis)
• Drug reactions
• Hypereosinophilic syndrome
• Malignancies (Hodgkin lymphoma)
• Collagen vascular diseases

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CASE 8

1. Markedly elevated WBC (1,25,000/cumm) with full myeloid spectrum (myelocytes, metamyelocytes, band forms, blasts) = leukaemoid-type picture characteristic of CML
2. Massive splenomegaly = hallmark of CML (extramedullary haematopoiesis in spleen)
3. Basophilia (5%) = characteristic of CML - basophilia in peripheral blood is a key feature
4. Left shift (myelocytes 21%, metamyelocytes 9%, bands 11%) = maturation arrest with release of immature cells into blood
5. Blast count only 2% = chronic phase CML (blasts <10%)

• t(9;22)(q34;q11) - Philadelphia chromosome
• Creates the BCR-ABL1 fusion gene on chromosome 22
• BCR-ABL1 protein has constitutive tyrosine kinase activity, driving uncontrolled myeloid proliferation
• Detected by: FISH, PCR for BCR-ABL1 transcript, or conventional karyotyping

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CASE 9

1. Myeloblasts 35% (>20% required for AML diagnosis per WHO criteria) = diagnostic
2. Pancytopenia (Hb 8.5, platelets 75,000, low neutrophils) = bone marrow infiltration by blasts crowding out normal haematopoiesis
3. Gum bleeding + petechial rash = thrombocytopenia causing mucosal and skin bleeding
4. Fever = increased susceptibility to infection due to neutropenia
5. Hepatosplenomegaly = leukaemic infiltration of organs
6. High WBC (135,000) with blasts = hyperleukocytosis

• Large blasts with high N:C ratio, prominent nucleoli (1-4 nucleoli)
• Auer rods (in AML subtypes, especially M1-M4)
• Anaemia (normocytic normochromic)
• Thrombocytopenia
• Neutropenia

• Hypercellular marrow

• 20% myeloblasts (may reach 60-90%)

• Auer rods in blasts
• Reduced normal erythroid, megakaryocytic, and granulocytic precursors
• MPO (Myeloperoxidase) positive blasts on cytochemistry

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CASE 10

• (Haemophilia B/Factor IX deficiency is also possible - identical clinical picture)

1. Prolonged aPTT + Normal PT + Normal BT = intrinsic pathway defect - consistent with Factor VIII, IX, or XI deficiency
2. Haemarthrosis = bleeding into joints = classic presentation of haemophilia; synovial lining is rich in plasminogen activator; joints are exposed to trauma
3. Haematoma formation after IM injections = deep tissue bleeding after minimal trauma = severe factor deficiency
4. X-linked recessive inheritance - affects males, carried by females (maternal relatives had bleeding) - Haemophilia A & B are both X-linked
5. Age 5, male child = typical presentation age

• X-linked recessive
• Gene located on X chromosome (Xq28 for Factor VIII - Haemophilia A; Xq27 for Factor IX - Haemophilia B)
• Males (XY) affected; females (XX) are carriers
• Affected fathers cannot pass it to sons (sons get Y from father)
• Carrier mothers pass to 50% of sons

• Inhibitor development (most serious) - antibodies against infused factor VIII/IX (occurs in 20-30% of severe haemophilia A patients)
• Transfusion-transmitted infections - HIV, Hepatitis B, Hepatitis C (historical, from pooled plasma products before screening)
• Allergic/anaphylactic reactions to factor concentrates
• Iron overload from repeated transfusions
• Thrombosis - with bypassing agents (aPCC, rFVIIa)
• Joint destruction (haemophilic arthropathy) despite treatment

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CASE 11

1. Microcytic hypochromic indices - MCV 60 fl (normal 80-100 fl), MCH 22 pg (normal 27-32 pg), MCHC 25% (normal 32-36%) = classic IDA pattern
2. Koilonychia (spoon-shaped nails) - pathognomonic sign of chronic IDA; seen when Hb is severely low (as here: Hb 5 g%)

• Inadequate dietary intake (poor nutrition)
• Chronic blood loss - menorrhagia (most common in women of reproductive age), GI bleeding (peptic ulcer, hookworm)
• Malabsorption - coeliac disease, post-gastrectomy
• Increased demand - pregnancy, infancy, adolescence
• Hookworm infestation

• Serum iron: decreased (< 60 μg/dl)
• Serum ferritin: decreased (< 12 μg/L) - most sensitive early indicator
• TIBC (Total Iron Binding Capacity): increased
• Serum transferrin saturation: decreased (<15%)
• Free erythrocyte protoporphyrin (FEP): elevated
• Reticulocyte count: low (hypoproliferative)
• Peripheral smear: pencil cells, target cells, anisocytosis, poikilocytosis
• RDW: increased (anisocytosis)
• Bone marrow: absent iron stores (Prussian blue stain negative)

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CASE 12

1. MCV 110 fl (macrocytic - normal 80-100 fl) = megaloblastic picture from impaired DNA synthesis due to B12 deficiency
2. Peripheral neuropathy + knuckle pigmentation - B12 deficiency causes subacute combined degeneration of spinal cord (dorsal and lateral column demyelination); folate deficiency does NOT cause neuropathy. Knuckle pigmentation is a feature associated with B12 deficiency in darker-skinned individuals

• Strict vegetarian/vegan diet (B12 found only in animal products) - most common cause globally
• Pernicious anaemia - autoimmune destruction of gastric parietal cells → loss of Intrinsic Factor (IF) → B12 malabsorption
• Gastrectomy / gastric bypass
• Crohn's disease (terminal ileum involvement - site of B12 absorption)
• Tapeworm (Diphyllobothrium latum) - competes for B12
• Fish diet without animal products (in some regions)
• Metformin use (impairs B12 absorption)

• Hypercellular marrow
• Megaloblasts (large erythroblasts with open, fine "lacy" chromatin and cytoplasmic-nuclear maturation asynchrony - cytoplasm matures faster than nucleus)
• Giant metamyelocytes and band forms (giant neutrophilic precursors)
• Hypersegmented megakaryocytes
• Increased M:E ratio initially; then decreased as megaloblastic change progresses
• "Biscuit tin lid" / sieve-like nuclear chromatin
• Ineffective erythropoiesis (intramedullary haemolysis)

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CASE 13 (Repeat of Case 12 - identical case, identical answer)

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CASE 14

1. Sternal tenderness = bone marrow expansion from leukaemic infiltration causing bone pain and sternal tenderness (classic sign of acute leukaemia)
2. WBC 1,00,000 + Hb 8 + Platelets 40,000 = hyperleukocytosis with pancytopenia - massive proliferation of blasts replacing normal marrow elements

• Myeloperoxidase (MPO) - Positive in AML (M1-M4), negative in ALL; most specific for myeloid lineage
• Sudan Black B (SBB) - Stains lipids/phospholipids in granules; positive in AML M1-M4
• Non-specific esterase (NSE / Alpha-naphthyl acetate esterase) - Strongly positive in monocytic leukaemia (AML M4, M5); inhibited by sodium fluoride
• Chloroacetate esterase (Specific esterase / Leder stain) - Positive in granulocytic lineage (M1-M3)
• PAS (Periodic Acid-Schiff) - Block positivity in ALL (lymphoblasts); diffuse in AML erythroblasts (M6)
• TdT (Terminal Deoxynucleotidyl Transferase) - Positive in ALL; usually negative in AML

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CASE 15

1. Child + generalised lymphadenopathy = ALL is the most common leukaemia in children (peak age 2-5 years); lymphadenopathy is more prominent in ALL than AML
2. Prolonged BT + Normal CT with thrombocytopenia - BT prolonged due to thrombocytopenia (platelet count 50,000); CT (whole blood clotting time) is normal because clotting factors are intact (intrinsic pathway normal) - this pattern fits thrombocytopenia, consistent with ALL replacing megakaryocytes

• L1: Small uniform lymphoblasts (most common in children)
• L2: Large heterogeneous lymphoblasts (more common in adults)
• L3: Large cells with vacuoles (Burkitt-type ALL)

• B-cell ALL (75-80%): Pre-B ALL (CD10+, CD19+, TdT+)
• T-cell ALL (15-20%): CD2, CD3, CD7 positive; adolescent males
• Mature B-cell ALL (Burkitt): Surface Ig+, EBV associated

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CASE 16

1. Elderly male (85 yrs) + generalised lymphadenopathy + hepato-splenomegaly = CLL is the most common leukaemia in the elderly (median age 65-70); lymphadenopathy and organomegaly are hallmarks
2. WBC 50,000 with absolute lymphocytosis + preserved platelets (2,50,000) = indolent proliferation of mature small lymphocytes without marked thrombocytopenia (early/intermediate CLL)

• Predominance of small mature lymphocytes
• "Smudge cells" or "basket cells" = fragile CLL lymphocytes ruptured during smear preparation (pathognomonic)
• Mild anaemia
• Lymphocytes have condensed ("soccer ball") chromatin

• Viral infections: Infectious mononucleosis (EBV), CMV, HIV, Hepatitis, Pertussis (whooping cough - marked lymphocytosis)
• Bacterial: Tuberculosis, Brucellosis, Typhoid (relative lymphocytosis)
• Pertussis (Bordetella) - extreme lymphocytosis in children
• Toxoplasmosis
• Post-splenectomy

• CLL (most common)
• ALL
• Non-Hodgkin Lymphoma (leukaemic phase)
• Adult T-cell Leukaemia/Lymphoma (HTLV-1)
• Hairy Cell Leukaemia
• Prolymphocytic leukaemia

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CASE 17

1. Pathologic fracture + multiple punched-out osteolytic skull lesions = myeloma cells secrete osteoclast-activating factors (RANKL, IL-6) causing localised bone destruction → "punched-out" lesions on X-ray
2. Bence Jones protein in urine (protein precipitates at 60°C, redissolves at 100°C = Bence Jones proteinuria) = free immunoglobulin light chains (κ or λ) secreted by myeloma plasma cells; filtered by kidneys

• Serum protein electrophoresis (SPEP) - shows M-band (monoclonal spike) in gamma region
• Bone marrow biopsy - shows >10% clonal plasma cells (often >30%)
• Urine immunofixation electrophoresis (for Bence Jones protein typing)
• Serum free light chain assay (κ/λ ratio)
• Beta-2 microglobulin (staging)
• LDH
• FISH/cytogenetics for t(4;14), t(14;16), del17p

• ESR is markedly elevated (often > 100 mm/hr, sometimes > 140 mm/hr)
• Reason: Myeloma cells secrete large amounts of abnormal immunoglobulin (M-protein/paraprotein). These immunoglobulins cause rouleaux formation (RBCs stack like coins due to reduced negative surface charge from protein coating). Rouleaux increase ESR because stacked RBCs sediment faster than individual cells. The fibrinogen and other acute phase proteins also contribute.

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CASE 18

1. Painful crises (vaso-occlusive episodes) - pain in abdomen, joints, fingers/toes (dactylitis) since early childhood = classic sickle cell pain crises due to microvascular occlusion by sickled cells
2. History of jaundice + reticulocytosis + anaemia (Hb 8 g%) = chronic haemolytic anaemia with compensatory increased RBC production (reticulocytosis) and unconjugated hyperbilirubinaemia causing jaundice

• Haemoglobin electrophoresis - shows HbS band; absence of HbA; may have HbF (gold standard)
• Sickling test (Sodium metabisulphite test) - induces sickling in deoxygenated conditions
• Solubility test (Sickledex/Itano test) - HbS is insoluble in deoxygenated phosphate buffer, forms turbid solution
• HPLC (High Performance Liquid Chromatography) - quantifies HbS, HbF, HbA2
• Peripheral smear: sickle cells, target cells, Howell-Jolly bodies
• DNA analysis (PCR for beta-globin mutation)

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CASE 19

1. Isolated thrombocytopenia (30,000/cumm) with normal Hb and WBC = isolated platelet destruction without bone marrow suppression = characteristic of ITP (autoimmune destruction of platelets by anti-platelet IgG antibodies)
2. Menorrhagia in young woman = prolonged/heavy bleeding due to thrombocytopenia → increased menstrual blood loss; a common presentation of ITP in females of reproductive age

• Aplastic anaemia
• Leukaemia / bone marrow infiltration
• Chemotherapy / radiation
• B12/folate deficiency (ineffective megakaryopoiesis)
• Viral infections (HIV, CMV)

• ITP (primary)
• Secondary ITP: SLE, CLL, HIV
• Drug-induced (heparin-induced - HIT, quinine, sulphonamides)
• Post-transfusion purpura
• Neonatal alloimmune thrombocytopenia

• DIC (consumption)
• TTP/HUS (microangiopathic)
• Hypersplenism (sequestration)

• Massive transfusion

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CASE 20

1. CD30+ and CD15+ - these are the immunohistochemical markers of Reed-Sternberg cells and their mononuclear variants (Hodgkin cells); CD30+/CD15+ is diagnostic of classical Hodgkin lymphoma
2. B symptoms (fever, night sweats, weight loss >10%) + cervical lymphadenopathy + pain in lymph node after alcohol consumption = Pel-Ebstein fever and alcohol-induced pain are classic features of Hodgkin lymphoma

• Nodular Lymphocyte Predominant HL (NLPHL) - "Popcorn cells" (LP cells); CD20+, CD30-, CD15-; best prognosis

• Classic Reed-Sternberg (RS) cell - large binucleate/multinucleate cell with two large "owl-eye" nucleoli (one in each lobe); CD30+, CD15+
• Mononuclear Hodgkin cell (RS variant)
• Lacunar cell - RS variant in Nodular Sclerosis; appears to sit in "lacunae" due to tissue processing artefact
• Lymphocytic/Histiocytic (L&H) cells / "Popcorn cells" - in NLPHL; multilobated nucleus resembling popcorn; CD20+, CD30-, EMA+
• Pleomorphic RS cells - in lymphocyte-depleted subtype

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CASE 21

1. CD45+ (LCA), CD20+ (B-cell marker), BCL6+ = markers of germinal centre-derived B-cell lymphoma; BCL6 is a transcription factor expressed in germinal centre cells - positive in DLBCL (GCB subtype)
2. Rapidly enlarging ileal lymph node in elderly male = DLBCL is the most common aggressive NHL in adults; extranodal presentation (ileum is a common extranodal site, related to Peyer's patches)

• Follicular Lymphoma (most common indolent NHL; t(14;18), BCL2+)
• Mantle Cell Lymphoma (t(11;14), Cyclin D1+; CD5+; aggressive)
• Marginal Zone Lymphoma (MALT lymphoma - H. pylori associated gastric; Splenic MZL; Nodal MZL)
• Burkitt Lymphoma (t(8;14), MYC rearrangement; "starry sky" pattern; CD10+, BCL6+, BCL2-)
• Small Lymphocytic Lymphoma (SLL) (tissue equivalent of CLL)
• Primary Mediastinal Large B-Cell Lymphoma (young women, mediastinal mass)
• Lymphoplasmacytic Lymphoma / Waldenström's Macroglobulinaemia (IgM paraprotein)

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CASE 22

1. "Crew-cut" appearance on skull X-ray = pathognomonic of severe haemolytic anaemia with compensatory erythroid marrow expansion into the skull diploë; the trabeculae appear as perpendicular striations resembling a crew cut
2. Elevated HbF, elevated HbA2, reduced/absent HbA on electrophoresis = hallmark of beta-thalassaemia; homozygous beta-gene mutations result in absent/reduced beta-globin chains; HbF (α2γ2) and HbA2 (α2δ2) compensate

• Beta-Thalassaemia Minor (Trait) - heterozygous; mild hypochromic microcytic anaemia; Hb usually > 10 g%; HbA2 > 3.5% (diagnostic)
• Beta-Thalassaemia Intermedia - intermediate severity; no transfusion dependence usually
• Alpha-Thalassaemia Trait - deletion of 1-2 alpha genes; silent or mild anaemia
• HbH Disease - deletion of 3 alpha genes; moderate haemolytic anaemia; HbH on electrophoresis
• Hydrops Fetalis (Alpha-Thalassaemia Major) - deletion of all 4 alpha genes

• Caused by deletion of all 4 alpha-globin genes (--/-- genotype)
• No alpha chains can be produced → no functional foetal haemoglobin (HbF = α2γ2) or adult Hb
• Results in Haemoglobin Bart's (γ4) - has very high O2 affinity, cannot deliver O2 to tissues
• Causes: severe intrauterine hypoxia → generalised oedema, ascites, pleural effusions = "hydrops"
• Stillbirth or death shortly after birth
• Mother at risk of pre-eclampsia and difficult delivery

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CASE 23

• Microcytic, hypochromic red cells (decreased MCV, MCH, MCHC)
• Increased central pallor (area of central pallor >1/3 of cell diameter)
• Anisocytosis (variation in RBC size - elevated RDW)
• Poikilocytosis: pencil cells, target cells, elliptocytes
• Reduced RBC count
• Normal/low platelet count or mild thrombocytosis (reactive)
• Normal WBC morphology

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CASE 24: Peripheral Smear Findings in Specific Clinical Conditions

A. 55-year-old male: Acute MI

• Leucocytosis (neutrophilia) - reactive leukocytosis from myocardial necrosis and stress response (catecholamine-mediated demargination)
• Left shift (band neutrophils)
• Toxic granulation in neutrophils
• May see slight thrombocytosis or activated platelets
• RBC morphology relatively normal

B. 10-year-old: Acute Appendicitis

• Neutrophilic leucocytosis (most prominent finding) - bacterial inflammation triggers bone marrow granulocyte release
• Left shift (band forms, metamyelocytes)
• Toxic granulation, Dohle bodies in neutrophils
• Normal RBC morphology

C. 1-year-old: Whooping Cough (Pertussis - Bordetella pertussis)

• Marked absolute lymphocytosis - WBC can reach 20,000-100,000/μL (characteristic)
• Predominance of small mature lymphocytes (lymphocyte-like cells with little cytoplasm)
• Pertussis toxin causes lymphocyte recirculation inhibition, accumulating them in blood
• This is the only bacterial infection causing extreme lymphocytosis (can mimic ALL)

D. 50-year-old male: Pulmonary TB (Cavitary lesion, apex, weight loss)

• Anaemia of chronic disease (normocytic normochromic or mild hypochromic microcytic)
• Relative lymphocytosis (monocytosis may occur)
• Mild leucocytosis or normal WBC
• Elevated ESR (non-specific)
• Monocytosis (classic for mycobacterial infections - TB is an intracellular granulomatous infection)
• Thrombocytosis (reactive, acute phase)

E. Chronic Asthmatic (Exacerbation)

• Eosinophilia - hallmark of allergic conditions; eosinophils mediate allergic inflammation (IgE-mast cell pathway activates eosinophil recruitment)
• Normal/mild leucocytosis
• If on steroids: eosinopenia + neutrophilia (steroids redistribute eosinophils and increase neutrophils)
• Normal RBC morphology

F. 37-year-old Pregnant Woman (Antenatal Screening)

• Physiological anaemia of pregnancy - dilutional anaemia (plasma volume expands >RBC mass); normocytic or mild macrocytic
• Leucocytosis (neutrophilia - physiological in pregnancy)
• Thrombocytopenia (gestational thrombocytopenia - mild, > 70,000)
• If iron-deficient: microcytic hypochromic picture (common in pregnancy due to increased iron demand)
• If B12/folate deficient: macrocytic changes

G. 60-year-old Diabetic: Cellulitis of Leg

• Neutrophilic leucocytosis (bacterial infection)
• Left shift (band forms, metamyelocytes)
• Toxic granulation, Dohle bodies, cytoplasmic vacuolation in neutrophils
• Diabetics may show more pronounced leucocytosis and toxic changes due to impaired immune response
• Normal RBC unless concurrent IDA/anaemia of chronic disease

H. 35-year-old Lady: Petechial Rash + Bleeding Gums - ITP

• Isolated thrombocytopenia (very low platelet count, often <20,000/cumm in ITP with bleeding)
• Large/giant platelets (megathrombocytes) - compensatory from increased megakaryocyte activity
• Normal RBC morphology (no fragmentation - distinguishes from TTP/HUS)
• Normal WBC count and morphology
• No anaemia (unless secondary blood loss)
• Smudge cells absent (helps differentiate from CLL)

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CASE 25

• Microcytic hypochromic RBCs
• Pencil cells
• Target cells
• Anisocytosis, poikilocytosis
• Increased central pallor

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CASE 26

• Oval macrocytes
• Hypersegmented neutrophils (>5 lobes)
• Anisocytosis, poikilocytosis

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CASE 27

• Microcytic hypochromic red cells (MCV and MCH low)
• Target cells (codocytes) - prominent due to excess alpha chains forming abnormal membranes
• Nucleated red blood cells (NRBC/erythroblasts) - from extramedullary erythropoiesis
• Poikilocytosis (teardrop cells, elliptocytes)
• Polychromasia (reticulocytosis)
• Basophilic stippling
• Howell-Jolly bodies (functional hyposplenism)
• Anaemia (Hb 4-7 g%)

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CASE 28

• Mother carries one abnormal beta-globin gene; mildly anaemic with elevated HbA2

• Severe microcytic hypochromic anaemia (Hb < 7)
• Target cells (numerous)
• Nucleated RBCs (erythroblasts)
• Basophilic stippling
• Polychromasia
• Poikilocytosis (teardrop, elliptocytes)

• Mild hypochromic microcytic anaemia (Hb 10-12 g%)
• Few target cells
• Mild anisocytosis
• HbA2 > 3.5% on electrophoresis

• In thalassaemia major, severe haemolytic anaemia causes compensatory expansion of erythroid bone marrow
• The marrow expands into the outer table of the skull (diploë), pushing the outer cortex outward
• This creates perpendicular trabecular striations radiating outward from the skull inner table
• Resembles the short bristles of a crew-cut haircut on X-ray
• Also seen in sickle cell disease, hereditary spherocytosis, severe IDA

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CASE 29

• Anti-D serum used
• Agglutination = Rh positive (D antigen present)
• No agglutination = Rh negative

• IgM (Isohemagglutinins)
• Naturally occurring; do not require prior sensitisation
• Can fix complement and cause intravascular haemolysis (ABO incompatibility transfusion reactions)

• IgG
• Immune antibody formed after sensitisation (pregnancy or transfusion)
• Can cross placenta (causes Haemolytic Disease of the Newborn - HDN)
• Cannot fix complement directly

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CASE 30

• M-protein spike in gamma region (monoclonal band)

1. Bone marrow biopsy (confirms >10% clonal plasma cells)
2. Serum free light chain assay (κ:λ ratio)
3. Full body CT/PET-CT (skeletal survey for lytic lesions)
4. Beta-2 microglobulin and LDH (staging)

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CASE 31

• Monoclonal (M) band/spike in the gamma globulin region (or beta region for IgA myeloma)
• Normal immunoglobulin fractions (IgG, IgA, IgM) are reduced (immune paresis)
• Tall, narrow, symmetric spike distinguishes it from polyclonal hypergammaglobulinaemia

• Multiple, discrete, round "punched-out" osteolytic lesions scattered throughout the skull
• No sclerotic rim (purely lytic, osteoclast-mediated)
• "Pepper-pot" skull or "Rain-drop skull" pattern
• May also show generalised osteoporosis

• Bence Jones protein - free monoclonal immunoglobulin light chains (κ or λ)
• Precipitates on heating at 56-60°C and redissolves at 100°C (classic heat test)
• Confirms diagnosis when serum electrophoresis shows M-band
• Can cause cast nephropathy (myeloma kidney) → renal failure
• Proteinuria on dipstick (though dipstick detects albumin better than light chains)

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CASE 32

• If microcytic, hypochromic with pencil cells → IDA
• If microcytic with target cells + basophilic stippling → Thalassaemia

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CASE 33

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CASE 34

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CASE 35

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Note: Cases 32-35 are image-based slides. The microscopy images could not be rendered here, but the diagnostic criteria and cell identification principles for each possible finding are provided above. Apply the morphological features described throughout these answers to the respective images.