1. Sickle cell anemia (showing sickle/drepanocytic RBCs and target cells).
2. Hydroxyurea (15–20 mg/kg/day).
3. Primary prevention of stroke:
   • Annual Transcranial Doppler (TCD) screening from 2 to 16 years of age (monitoring time-averaged mean maximum velocity [TAMMV] in distal internal carotid/middle cerebral artery).
   • If TCD velocity $>200\text{ cm/s}$, initiate chronic transfusion therapy to maintain $\text{HbS}<30\mathrm{\%}$.
4. Third-generation cephalosporin (e.g., Ceftriaxone/Cefotaxime) PLUS a macrolide (e.g., Azithromycin) to cover atypical pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae).
5. Renal medullary carcinoma (strongly associated with sickle cell trait and disease).

1. Diamond-Blackfan anemia (DBA / Congenital pure red cell aplasia).
2. Ribosomopathy (mutations in ribosomal protein genes, e.g., RPS19, RPL5) causing intrinsic deficiency and apoptosis of erythroid progenitor cells (CFU-E / BFU-E) with insensitivity to erythropoietin.
3. Transient Erythroblastopenia of Childhood (TEC).
4. Differentiating points between DBA and TEC:
   • Age of onset: DBA presents $<6$ months (often at birth), TEC occurs after 6 months (1–3 years).
   • Congenital anomalies: Present in DBA (40–50%, e.g., triphalangeal thumb, craniofacial defects); absent in TEC.
   • RBC indices & markers: MCV is elevated (macrocytic), HbF elevated, and erythrocyte adenosine deaminase (eADA) elevated in DBA; normal in TEC.
   • Preceding viral illness: Absent in DBA; common in TEC.
5. Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), osteosarcoma.

Anterior Mediastinum (4 T's + Lymphoma):

• Lymphoma (Hodgkin lymphoma, Non-Hodgkin lymphoma / T-ALL)
• Thymoma / Thymic hyperplasia / Thymic cyst
• Teratoma / Germ cell tumors
• Thyroid masses / substernal goiter
• Vascular: Aneurysm, hemangioma, lipoma, cystic hygroma

Middle Mediastinum:

• Lymphadenopathy (Tuberculosis, Sarcoidosis, Lymphoma, Histoplasmosis, fungal infections)
• Bronchogenic cyst, pericardial cyst, enteric duplication cyst
• Vascular lesions: Great vessel anomalies, pulmonary artery enlargement
• Diaphragmatic hernia (Morgagni hernia)

Posterior Mediastinum:

• Neurogenic tumors: Neuroblastoma, ganglioneuroma, ganglioneuroblastoma, schwannoma, neurofibroma
• Ewing sarcoma / Askin tumor of chest wall
• Thoracic meningocele / Neurenteric cyst / Enterogenous cyst
• Posterior mediastinal lymphoma / rhabdomyosarcoma

1. Acute Myeloid Leukemia (AML) (showing myeloblasts with Auer rods / monoblasts).
2. Poor prognostic factors in AML:
   • High initial WBC count ($>100,000/{\text{mm}}^3$)
   • Adverse cytogenetics: Monosomy 7, monosomy 5, del(5q), 11q23 (MLL) rearrangements, complex karyotype ($\ge 3$ abnormalities)
   • Molecular mutations: FLT3-ITD mutation (high allelic ratio)
   • Secondary AML (therapy-related or evolving from prior MDS/aplastic anemia)
   • Poor response to induction / Persistent minimal residual disease (MRD) after induction

1. Pearson marrow-pancreas syndrome (a mitochondrial deletion disorder).
2. Diagnostic investigations:
   • Bone marrow aspiration: Shows macrocytic anemia, ringed sideroblasts (Perls' Prussian blue stain), and vacuolization of erythroid and myeloid precursor cells.
   • Mitochondrial DNA (mtDNA) analysis: Shows large single mitochondrial DNA deletion/duplication.
3. Treatment:
   • Supportive: Packed RBC and platelet transfusions, G-CSF for severe neutropenia
   • Pancreatic enzyme replacement therapy (for exocrine pancreatic insufficiency)
   • Insulin therapy (for neonatal/infantile diabetes mellitus)
   • Management of metabolic/lactic acidosis and vitamin/carnitine supplementation

1. Classification by Factor VIII level:
   • Severe: $<1\mathrm{\%}$ ($<0.01\text{ IU/mL}$)
   • Moderate: $1–5\mathrm{\%}$ ($0.01–0.05\text{ IU/mL}$)
   • Mild: $>5–40\mathrm{\%}$ ($0.05–0.40\text{ IU/mL}$)
2. Factor VIII for hemarthrosis:
   i. Target level: $40–50\mathrm{\%}$ ($0.4–0.5\text{ IU/mL}$)
   ii. Dose: $20–25\text{ IU/kg}$ IV (1 unit/kg raises factor VIII by 2%), repeated every 12–24 hours until symptoms resolve.
3. For major surgery:
   i. Target level: $100\mathrm{\%}$ ($1.0\text{ IU/mL}$) pre-op, maintained $>50\mathrm{\%}$ for 7–10 days post-op.
   ii. Dose: Loading dose of $50\text{ IU/kg}$ IV, followed by continuous infusion ($2–3\text{ IU/kg/hr}$) or $25–30\text{ IU/kg}$ every 8–12 hours.
4. Other precautions:
   • Avoid intramuscular (IM) injections and NSAIDs / Aspirin / antiplatelet agents.
   • Screen for inhibitor antibodies (Bethesda assay) and transfusion-transmitted infections (Hepatitis B, C, HIV).
   • Early joint rehabilitation / physiotherapy after acute bleed resolves.
5. Role of DDAVP (Desmopressin): Stimulates endogenous release of Factor VIII and vWF from endothelial Weibel-Palade bodies; effective in mild Hemophilia A (baseline $>5\mathrm{\%}$) for minor bleeds and dental procedures.

1. Sickle ${\beta }^{+}$-thalassemia (compound heterozygosity for HbS and ${\beta }^{+}$-thalassemia mutation).
2. Beta-thalassemia trait / minor ($\beta$-thalassemia carrier) (since father has sickle cell trait, the $\beta$-thalassemia gene was inherited from the mother).

Reference ranges on Hb electrophoresis/HPLC:

• Sickle Cell Anemia (HbSS): $\text{HbS }80-95\mathrm{\%}$, $\text{HbA }0\mathrm{\%}$, $\text{HbF }5-15\mathrm{\%}$, ${\text{HbA}}_2\text{ normal}$.
• Sickle Cell Trait (HbAS): $\text{HbA }55-60\mathrm{\%}$, $\text{HbS }35-40\mathrm{\%}$, ${\text{HbA}}_2\text{ normal}$.
• $\text{Sickle }{\beta }^0\text{-thalassemia}$: $\text{HbS }80-90\mathrm{\%}$, $\text{HbA }0\mathrm{\%}$, ${\text{HbA}}_2>3.5\mathrm{\%}$, $\text{HbF }5-15\mathrm{\%}$.
• $\text{Sickle }{\beta }^{+}\text{-thalassemia}$: $\text{HbS }60-80\mathrm{\%}$, $\text{HbA }10-30\mathrm{\%}$, ${\text{HbA}}_2>3.5\mathrm{\%}$, $\text{HbF }3-10\mathrm{\%}$.

1. Neuroblastoma; Periorbital ecchymosis / "raccoon eyes" (due to retrobulbar metastatic infiltration and venous obstruction).
2. Associated conditions / syndromes:
   • Neurofibromatosis type 1 (NF-1)
   • Hirschsprung disease (congenital aganglionic megacolon)
   • Beckwith-Wiedemann syndrome
   • Central hypoventilation syndrome (Ondine curse)
   • Fetal hydantoin syndrome / Fetal alcohol syndrome
   • Opsoclonus-myoclonus-ataxia syndrome (paraneoplastic)

1. Polycythemia / Leukemoid reaction secondary to perinatal hypoxia/asphyxia (Secondary neonatal polycythemia).
2. Secondary polycythemia (hypoxia-driven increased erythropoietin production).
3. Diagnostic workup:
   • Venous hematocrit / packed cell volume (PCV $>65\mathrm{\%}$ defines polycythemia)
   • Arterial Blood Gas (ABG) to assess arterial oxygen saturation ($Sa{O}_2$)
   • Serum Erythropoietin (EPO) level (elevated in secondary polycythemia, low in primary)
   • Carboxyhemoglobin level, blood glucose, and serum calcium
   • Abdominal and renal USG (to rule out renal tumors/cystic lesions or hydronephrosis producing EPO)
   • Leukocyte Alkaline Phosphatase (LAP) score
   • JAK2 V617F mutation analysis (negative in secondary)

1. Slide A: Reed-Sternberg cell (classic "owl-eye" appearance) $\to$ Hodgkin Lymphoma. Slide B: L3 type lymphoblasts with deep basophilic cytoplasm and lipid vacuoles $\to$ Burkitt Lymphoma / Mature B-cell ALL.
2. "B symptoms" of Hodgkin Lymphoma:
   • Unexplained fever $>{38}^{\circ }\text{C}$ (including Pel-Ebstein fever)
   • Drenching night sweats
   • Unexplained weight loss $>10\mathrm{\%}$ of baseline body weight within 6 months
3. Prognosis: Burkitt lymphoma carries a good prognosis with modern intensive chemotherapy protocols ($>80-90\mathrm{\%}$ cure rate); however, if left untreated or with delayed therapy, it is one of the fastest-growing tumors with high risk of tumor lysis syndrome.

1. Vitamin K Deficiency Bleeding (VKDB) / Classic Hemorrhagic Disease of the Newborn (HDN).
2. Treatment:
   • Vitamin $K_1$ (Phytomenadione): 1 mg IV slowly (or SC).
   • Fresh Frozen Plasma (FFP): 10–15 mL/kg IV for acute active bleeding or severe hemorrhage.
   • Packed RBC transfusion if severe anemia / hemodynamic instability.
3. Coagulation cascade pathways:
   • Extrinsic pathway: Factor VII, Tissue Factor (Factor III).
   • Common pathway: Factor X, Factor V, Factor II (Prothrombin), Factor I (Fibrinogen), Factor XIII.
4. Coagulation factor numbers no longer in use:
   • Factor III (Tissue thromboplastin / Tissue factor - not a single plasma protein)
   • Factor IV (Calcium ions - not a protein)
   • Factor VI (Accelerin - proven to be the activated form of Factor V, i.e., Va).

1. Immune Thrombocytopenic Purpura (ITP / Primary Immune Thrombocytopenia).
2. First-line therapy:
   • Intravenous Immunoglobulin (IVIg): $0.8–1.0\text{ g/kg/day}$ for 1–2 days (or $0.4\text{ g/kg/day}$ for 5 days), OR
   • Intravenous Anti-D immunoglobulin ($50–75\text{ µg/kg}$ in Rh-positive, non-splenectomized patients), OR
   • Oral Prednisolone ($2–4\text{ mg/kg/day}$ for 1–2 weeks).
3. No, antibiotics have no role in acute ITP.
4. Small-sized platelets with thrombocytopenia: Wiskott-Aldrich syndrome (WAS / WASP gene mutation).
5. Platelet functional disorders:
   • Glanzmann thrombasthenia (deficiency of GPIIb/IIIa receptor)
   • Bernard-Soulier syndrome (deficiency of GPIb/IX/V receptor - large platelets)
   • Gray platelet syndrome / Storage pool deficiencies

1. Acute Myeloid Leukemia (AML) (specifically AML with granulocytic sarcoma / chloroma).
2. Myeloblasts with intracellular Auer rods (fused azurophilic granules).
3. Chloroma / Granulocytic sarcoma (Myeloid sarcoma / leukemic infiltration of orbit/skin: leukemia cutis).
4. Translocation $\text{t}(8;21)(\text{q}22;\text{q}22)$ ($RUNX1\text{-}RUNX1T1$) or $\text{inv}(16)$.

• 1. Microcytic with low reticulocyte $\to$ c. Lead poisoning / Iron deficiency anemia
• 2. Microcytic with high reticulocyte $\to$ f. Hereditary pyropoikilocytosis / Hemoglobin H disease
• 3. Macrocytic with low reticulocyte $\to$ e. Hypothyroidism / Vitamin $B_{12}$ deficiency
• 4. Macrocytic with high reticulocyte $\to$ b. Congenital dyserythropoietic anemia (or active hemolysis with reticulocytosis)
• 5. Normocytic with low reticulocyte $\to$ a. Chronic renal failure / Aplastic anemia
• 6. Normocytic with high reticulocyte $\to$ d. Hemolytic Uremic Syndrome (HUS) / Immune hemolytic anemia

(Match: 1-c, 2-f, 3-e, 4-b, 5-a, 6-d)

1. Diamond-Blackfan Anemia (DBA / Congenital pure red cell aplasia).
2. Elevated HbF levels (and elevated erythrocyte adenosine deaminase [eADA]).
3. Differential diagnoses:
   • Fanconi anemia
   • Transient erythroblastopenia of childhood (TEC)
   • Congenital dyserythropoietic anemia (CDA)
   • Parvovirus B19 induced red cell aplasia
4. Treatment:
   • Corticosteroids (Oral Prednisolone 2 mg/kg/day; effective in ~80%)
   • Chronic packed RBC transfusions with iron chelation therapy (for steroid non-responders)
   • Hematopoietic stem cell transplantation (HSCT - only curative modality)

1. True (Term infants experience a benign physiological nadir at 8–12 weeks, Hb 9–11 g/dL, requiring no therapy).
2. False (There is a physiologic down-regulation / reduced erythropoietin production in response to increased tissue oxygenation after birth).
3. True (In preterm infants, anemia of prematurity occurs earlier at 4–8 weeks and is more severe, Hb 7–9 g/dL).
4. True (Recombinant EPO, iron, protein, and vitamin E supplementation are used in anemia of prematurity).

(Answers: 1-True, 2-False, 3-True, 4-True)

1. False (Clinical pallor becomes apparent at $\text{Hb}<7–8\text{ g/dL}$, especially at conjunctiva and palmar creases).
2. False (Platelets may be elevated in mild-moderate IDA due to reactive thrombocytosis, but WBC count is typically normal).
3. True (ZPP $>80\text{ µmol/mol}$ heme indicates iron-deficient erythropoiesis and is useful for screening).
4. False (Serum ferritin is an acute-phase reactant; it is elevated in liver disease, inflammation, and infections even in the presence of iron deficiency).
5. False (Subjective improvement in appetite, mood, and alertness occurs within 24–48 hours due to replenishment of intracellular iron-containing enzymes).
6. True (Elemental iron alone is sufficient; routine vitamin combinations add cost without proven therapeutic advantage).
7. True (Pencil cells / cigar cells and elliptocytes are characteristic findings in severe microcytic hypochromic IDA).

(Answers: 1-False, 2-False, 3-True, 4-False, 5-False, 6-True, 7-True)

1. Hereditary Spherocytosis (HS); Autosomal dominant in 75% (mutations in ankyrin, band 3, $\beta$-spectrin).
2. Infection: Parvovirus B19 infection; Complication: Aplastic crisis (and hyperhemolytic / megaloblastic crisis).
3. Long-term complications: Pigment gallstones (cholelithiasis), splenomegaly with hypersplenism, leg ulcers, gout, growth retardation.
4. PBF: Microspherocytes (dense, round RBCs lacking central pallor). Other causes of spherocytes:
   • ABO incompatibility / autoimmune hemolytic anemia (AIHA)
   • Thermal injury / severe burns
   • Clostridial sepsis / snake bite envenomation
   • Hypophosphatemia / Microangiopathic hemolytic anemia
5. Diagnostic tests:
   • Eosin-5-maleimide (EMA) binding test by flow cytometry (gold standard, high sensitivity & specificity)
   • Osmotic fragility test (acidified glycerol lysis test)
6. Splenectomy guidelines:
   • Treatment of choice for moderate-to-severe HS, but delayed until $>5–6$ years of age to minimize post-splenectomy sepsis risk.
   • Not indicated in mild HS ($\text{Hb}>10–11\text{ g/dL}$, reticulocytes $<6\mathrm{\%}$).
   • Administer pneumococcal, meningococcal, and H. influenzae type b vaccinations at least 2–4 weeks prior, with lifelong prophylactic penicillin.

1. Emergency inpatient hospital admission (due to functional asplenia, fever with leukocytosis and hypotension indicates life-threatening encapsulated bacterial sepsis / pneumococcal bacteremia or acute splenic sequestration).
2. Wong-Baker FACES Pain Rating Scale (for younger children) or Numerical Rating Scale (NRS) / Visual Analog Scale (VAS) for older children.
3. Advances in pain reduction / disease modification:
   • Hydroxyurea (increases HbF, reduces vaso-occlusive crises)
   • Crizanlizumab (anti-P-selectin monoclonal antibody)
   • Voxelotor (HbS polymerization inhibitor)
   • L-glutamine (reduces oxidative stress)
4. Treatment of priapism:
   • Supportive: Hydration, analgesia, warm sitz bath, urination
   • If prolonged $>2–4$ hours: Aspiration of blood from corpus cavernosum and irrigation with dilute alpha-adrenergic agonist (e.g., phenylephrine or adrenaline / epinephrine)
   • Exchange transfusion / surgical shunt if refractory
5. Newborn screening: High-Performance Liquid Chromatography (HPLC) or Isoelectric Focusing (IEF) from dried blood spots (Guthrie card).

• Statement 1: True (Deficiency of NADH-cytochrome b5 reductase [CYB5R3] is the primary enzymatic cause).
• Statement 2: False (Clinical cyanosis becomes apparent when methemoglobin level exceeds $1.5\text{ g/dL}$ or $\sim 10-15\mathrm{\%}$ of total hemoglobin; normal reduced Hb produces cyanosis at $>5\text{ g/dL}$).
• Statement 3: True (Oral ascorbic acid 200–500 mg/day or riboflavin is effective for chronic maintenance).
• Statement 4: False (Ascorbic acid at recommended maintenance doses does not commonly induce nephrolithiasis in children).
• Statement 5: False (Methylene blue is CONTRAINDICATED in G6PD deficiency because it requires NADPH generated by G6PD to reduce to leukomethylene blue; in G6PD deficiency it can precipitate severe acute hemolysis).

(False statements: 2, 4, 5)

1. True (Ineffective erythropoiesis and intramedullary destruction of erythroblasts result in an inappropriately low reticulocyte count relative to the severe degree of anemia).
2. True (Extended RBC phenotyping before first transfusion prevents alloimmunization against minor blood group antigens).
3. True (NTBI and labile plasma iron [LPI] generate reactive oxygen species causing parenchymal organ damage).
4. True (T2* MRI of heart and liver has replaced liver biopsy as the non-invasive gold standard for monitoring tissue iron overload).
5. True (Myocardial iron overload leading to cardiomyopathy, heart failure, and fatal arrhythmias is the leading cause of mortality).

(All statements are True)

1. Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency with acute intravascular hemolytic crisis.
2. Precipitating drugs / agents:
   • Antimalarials: Primaquine, pamaquine, chloroquine
   • Antibacterials: Sulfonamides, co-trimoxazole, dapsone, nitrofurantoin, nalidixic acid
   • Analgesics: Aspirin (high doses), phenacetin
   • Chemicals: Naphthalene balls (mothballs), Methylene blue
   • Foods: Fava beans (favism)
3. X-linked recessive. Yes, females can be affected if homozygous, compound heterozygous, or heterozygous with skewed X-inactivation (Lyonization).
4. Diagnostic test: Quantitative G6PD spectrophotometric assay in red blood cells ($<10–30\mathrm{\%}$ of normal activity is diagnostic). (Note: Test during acute hemolytic episode may be falsely normal due to higher enzyme levels in surviving young reticulocytes; repeat after 2–3 months).
5. PBF findings: "Bite cells" (degmacytes), "blister cells", polychromasia, and Heinz bodies on supravital (methyl violet / crystal violet) staining.

1. Fanconi Anemia (FA).
2. Chromosomal breakage study / Diepoxybutane (DEB) and Mitomycin C (MMC) test on peripheral blood lymphocytes (demonstrating increased chromosome breaks, radial forms, and gaps).
3. Causes of pancytopenia with hypercellular / normocellular bone marrow:
   • Acute leukemia (ALL, AML)
   • Myelodysplastic syndromes (MDS)
   • Megaloblastic anemia (Vitamin $B_{12}$ / folate deficiency)
   • Hypersplenism
   • Hemophagocytic Lymphohistiocytosis (HLH)
   • Visceral leishmaniasis (Kala-azar)
   • Gaucher disease / Niemann-Pick disease
4. Future malignancies: Acute Myeloid Leukemia (AML), MDS, squamous cell carcinoma of head and neck, esophagus, and anogenital tract.
5. Treatment:
   • Allogeneic Hematopoietic Stem Cell Transplantation (HSCT - only curative therapy)
   • Androgens (e.g., Oxymetholone) and G-CSF for hematologic support
   • Supportive transfusions (leukoreduced, irradiated blood products)
   • Surveillance for secondary solid tumors.

1. Dyskeratosis Congenita (Zinsser-Cole-Engman syndrome, a telomere biology disorder).
2. Classic triad:
   • Reticulated / lacy hyperpigmentation of neck and upper chest
   • Nail dystrophy (ridging, splitting, pterygium)
   • Oral mucosal leukoplakia
3. Reticulated skin pigmentation (present in $>90\mathrm{\%}$ of patients).
4. Complications:
   • Progressive bone marrow failure / aplastic anemia
   • Pulmonary fibrosis
   • Liver cirrhosis
   • Malignancy: Myelodysplastic syndrome (MDS), AML, squamous cell carcinoma of mouth/esophagus
5. Treatment:
   • Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
   • Androgen therapy (Danazol / Oxymetholone to elongate telomeres and improve cytopenias)
   • Supportive hematologic care and cancer surveillance

1. Severe Aplastic Anemia (SAA) (likely pesticide-induced/acquired). Criteria for SAA met: Bone marrow cellularity $<25\mathrm{\%}$ plus at least 2 of: $\text{ANC}<500/\text{µL}$, $\text{Platelets}<20,000/\text{µL}$, $\text{Reticulocytes}<20,000/\text{µL}$ (or $<1\mathrm{\%}$).
2. Viral etiologies: Hepatitis viruses (Non-A, Non-B, Non-C post-hepatitis aplastic anemia), Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), Parvovirus B19, HIV.
3. Flow cytometry in Paroxysmal Nocturnal Hemoglobinuria (PNH): Deficiency / absence of GPI-anchored proteins: CD55 (DAF) and CD59 (MIRL) on granulocytes and red blood cells (using FLAER).
4. Treatment options:
   • Matched sibling donor (MSD) Hematopoietic Stem Cell Transplantation (treatment of choice for young patients)
   • Immunosuppressive therapy (IST): Antithymocyte globulin (ATG) + Cyclosporine + Eltrombopag + short-course steroids
5. Clonal evolution / future neoplastic risks: Myelodysplastic syndrome (MDS), Acute Myeloid Leukemia (AML), and Paroxysmal Nocturnal Hemoglobinuria (PNH).

1. von Willebrand Disease (vWD).
2. Yes, because plasma vWF and Factor VIII levels vary with ABO blood group (individuals with blood group O have $\sim 25–30\mathrm{\%}$ lower baseline vWF levels compared to non-O blood groups: $\text{AB}>\text{B}>\text{A}>\text{O}$).
3. Definitive diagnostic tests:
   • vWF Antigen (vWF:Ag) quantitative assay
   • Ristocetin cofactor activity (vWF:RCo) / platelet-binding activity
   • Factor VIII coagulant activity (FVIII:C)
   • vWF multimer analysis (for subtyping)
4. Treatment modalities:
   • Desmopressin (DDAVP) (effective in Type 1 vWD)
   • vWF-containing Factor VIII concentrates (e.g., Humate-P, Wilate) or recombinant vWF
   • Antifibrinolytics: Tranexamic acid, Epsilon-aminocaproic acid (EACA)
   • Combined oral contraceptives / Levonorgestrel IUD for menorrhagia

1. Investigations:
   • Contrast-enhanced CT (CECT) / MRI abdomen and pelvis
   • USG abdomen with Doppler
   • 24-hour urinary catecholamines: VMA and HVA (to differentiate from neuroblastoma)
   • Chest CT / X-ray (to assess pulmonary metastasis)
     Differential diagnoses: Wilms' tumor (Nephroblastoma) and Neuroblastoma.
2. Role of Urine R/M: Detects microscopic hematuria (present in up to 30–50% of Wilms' tumors due to renal pelvic/parenchymal invasion) and rules out UTI or proteinuria.
3. Prognostic factors in Wilms' tumor:
   • Histopathology: Favorable histology vs. Unfavorable / Anaplastic histology (most critical factor)
   • Stage of the disease at diagnosis (Stage I–V)
   • Age at diagnosis (better prognosis if $<2$ years)
   • Tumor weight / size ($<550\text{ g}$ favorable)
   • Molecular markers (loss of heterozygosity at 1p and 16q, 1q gain).
4. Nephrogenic rests: Foci of abnormally retained, persistent embryonal metanephric blastema beyond 36 weeks of gestation; they are premalignant precursors found in $\sim 35\mathrm{\%}$ of unilateral Wilms' tumors and nearly $100\mathrm{\%}$ of bilateral Wilms' tumors.

• 1. Hemorrhagic cystitis $\to$ Cyclophosphamide (due to metabolite acrolein; prevented with Mesna)
• 2. Acute dystonic reaction $\to$ Domperidone / Metoclopramide (dopamine D2 receptor antagonism)
• 3. Deranged clotting profile / Coagulopathy $\to$ L-asparaginase (inhibits hepatic synthesis of antithrombin III, protein C/S, and fibrinogen)
• 4. Hypokalemia $\to$ Amphotericin B (tubular leak)
• 5. "Red man syndrome" / Flushing $\to$ Vancomycin (histamine release with rapid infusion)
• 6. Megaloblastic anemia / Mucositis $\to$ Methotrexate (dihydrofolate reductase inhibition; rescued with folinic acid/leucovorin)
• 7. Cardiomyopathy $\to$ Doxorubicin (free radical mediated cumulative cardiotoxicity)

1. Clinical findings:
   • Image A: Gingival hypertrophy / hyperplasia.
   • Image B: Mucocutaneous / oral hyperpigmentation (melanoplakia).
2. Causes:
   • Gingival hypertrophy (Image A):
     • Phenytoin toxicity
     • Cyclosporine therapy
     • Calcium channel blockers (e.g., Amlodipine, Nifedipine)
     • Acute Monocytic Leukemia (AML-M4 / M5)
   • Oral hyperpigmentation (Image B):
     • Addison's disease (Primary adrenal insufficiency / high ACTH)
     • Peutz-Jeghers syndrome
     • Heavy metal toxicity (Lead line / Bismuth)
     • Drugs (e.g., Hydroxyurea, Cyclophosphamide, Clofazimine)

1. Phenytoin (causes macrocytic anemia by interfering with folate absorption and metabolism).
2. Hydroxyurea (induces macrocytosis / elevated MCV, which serves as a marker of drug adherence and efficacy).
3. Heparin (Heparin-Induced Thrombocytopenia [HIT type II], an immune-mediated reaction occurring 5–10 days post-exposure).
4. Co-trimoxazole (causes drug-induced marrow suppression / pancytopenia via antifolate activity).

1. Serum haptoglobin is markedly decreased / undetectable (depleted by binding free Hb); plasma methemalbumin and urinary hemosiderin/free hemoglobin are increased.
2. PBF findings: "Bite cells" (degmacytes), "blister/hemi-ghost cells", polychromasia, and Heinz bodies on supravital staining.
3. Post-splenectomy PBF findings: Howell-Jolly bodies (nuclear remnants), Pappenheimer bodies, Heinz bodies, target cells, and acanthocytes.
4. Management of hemolytic crisis:
   • Immediately discontinue offending drug/agent (Aspirin)
   • Maintain vigorous hydration and urine alkalinization to prevent renal tubular obstruction by hemoglobin casts
   • Packed RBC transfusion if severe anemia or cardiovascular compromise
   • Phototherapy / exchange transfusion in severe neonatal jaundice.

1. Hemophilia A (Factor VIII deficiency) or Hemophilia B (Factor IX deficiency). (Factor XIII deficiency can also present with umbilical cord bleeding, but has normal aPTT).
2. Severity classification by clotting factor level:
   • Severe: $<1\mathrm{\%}$ ($<0.01\text{ IU/mL}$) $\to$ spontaneous bleeds, frequent hemarthroses
   • Moderate: $1–5\mathrm{\%}$ ($0.01–0.05\text{ IU/mL}$) $\to$ bleeding with minor trauma
   • Mild: $>5–40\mathrm{\%}$ ($0.05–0.40\text{ IU/mL}$) $\to$ bleeding only with major trauma / surgery
3. Genetic basis: Hemophilia is an X-linked recessive disorder. The mother is an obligate or potential carrier ($X^H{X}^h$) who inherited the mutant allele from a common ancestor. Her sister also inherited the mutated X chromosome and transmitted it to her son ($X^{h}Y$). The maternal uncle passes his Y chromosome to his son (who receives an X from his unrelated mother) and therefore the maternal uncle's son cannot inherit the X-linked disease.
4. Use of AMICAR (Epsilon-aminocaproic acid) / Tranexamic acid: Antifibrinolytic agent that competitively inhibits plasminogen activation and prevents clot lysis. It is particularly useful for mucosal bleeding (dental extractions, oral/nasal bleeds) by blocking salivary/mucosal fibrinolytic enzymes.

Parameter	Iron Deficiency Anemia	Anemia of Chronic Disease	$\beta$-Thalassemia Trait	Sideroblastic Anemia
Serum Iron	Low	Low	Normal / High	High
TIBC	High	Low	Normal	Low / Normal
Transferrin Saturation	Low ($<15\mathrm{\%}$)	Normal / Low ($15–30\mathrm{\%}$)	Normal ($30–50\mathrm{\%}$)	High ($>80–100\mathrm{\%}$)
Serum Ferritin	Low ($<12–15\text{ µg/L}$)	High / Normal	Normal / High	Very High

• 1 $\to$ b. Iron deficiency anemia
• 2 $\to$ a. Anemia of chronic disease
• 3 $\to$ c. Beta-thalassemia trait
• 4 $\to$ d. Sideroblastic anemia

1. Commonest malignant abdominal mass in children: Neuroblastoma / Wilms' tumor (Wilms is commonest renal malignant mass). Commonest non-malignant mass: Fecal impaction / Hydronephrosis / Multicystic dysplastic kidney.
2. Differential diagnoses: Wilms' tumor (Nephroblastoma) and Neuroblastoma. Most probable diagnosis: Wilms' tumor (smooth, intrarenal, does not cross midline, hematuria, no calcification).
3. Hypertension (elevated BP) due to renal ischemia and hyperreninism caused by compression of the renal vasculature by the tumor mass.
4. Associated syndromes:
   • WAGR syndrome (Wilms, Aniridia, Genitourinary anomalies, Retardation)
   • Beckwith-Wiedemann syndrome (BWS - hemihypertrophy, macroglossia, omphalocele)
   • Denys-Drash syndrome (Wilms, pseudohermaphroditism, progressive glomerulopathy)
5. Prognosis: Excellent; overall 5-year survival rate for favorable histology Wilms' tumor exceeds $85–90\mathrm{\%}$.

1. Differential diagnoses:
   • Reactive / infective lymphadenitis (bacterial, e.g., Staphylococcus, Streptococcus)
   • Tubercular lymphadenitis (Scrofula)
   • Non-tuberculous mycobacterial (NTM) lymphadenitis
   • Cat scratch disease (Bartonella henselae)
   • Infectious mononucleosis (EBV / CMV)
   • Lymphoma (Hodgkin / Non-Hodgkin)
2. First-line management: Oral course of broad-spectrum antibiotic covering Staphylococcus aureus and Streptococcus pyogenes (e.g., Amoxicillin-Clavulanate or Cephalexin for 10–14 days) and observation.
3. Reactive infective lymphadenitis (post-viral/upper respiratory tract infection).
4. If no regression after 10–14 days: Perform Fine Needle Aspiration Cytology (FNAC) or Excisional Lymph Node Biopsy for histopathology, GeneXpert (CBNAAT), and mycobacterial/fungal culture.
5. BCG protection: Provides $\sim 70–80\mathrm{\%}$ protection against severe childhood tuberculosis (TB meningitis and miliary TB), $\sim 50\mathrm{\%}$ against pulmonary TB, and minimal to variable ($<10\mathrm{\%}$) protection against non-tuberculous mycobacteria.

1. Complete Blood Count (CBC) with absolute neutrophil count (ANC) and paired blood cultures (from central line and peripheral vein) to diagnose febrile neutropenia and identify bacteremia.
2. Febrile neutropenia with central line-associated bloodstream infection (CLABSI). YES, this is a medical emergency requiring immediate hospitalization and empiric broad-spectrum IV antibiotics within 1 hour.
3. Risk factors for infection:
   • Severe neutropenia ($\text{ANC}<500/\text{µL}$ or expected nadir $<100/\text{µL}$)
   • Mucositis / breakdown of mucosal barriers
   • Indwelling central venous catheter
   • Immunosuppression from chemotherapy and corticosteroids
   • Malnutrition and prolonged hospital stay
4. Management:
   • Immediate inpatient admission
   • Obtain blood cultures from all lumens of central line and peripheral vein, urine culture, and swab of catheter exit site
   • Prompt empirical IV monotherapy with anti-pseudomonal $\beta$-lactam (e.g., Piperacillin-Tazobactam, Cefepime, or Meropenem) $\pm$ Vancomycin (indicated due to central line site inflammation)
   • IV fluid hydration, strict barrier precautions, and antipyretics (avoid NSAIDs/rectal suppositories).