Pediatrics
Final Professional MBBS — Pediatrics. Complete question bank: Long Questions (10 marks) and Short Notes (5 marks) across all 15 systems, with clinical pearls, drug doses, staging tables, mnemonics and key-point recaps.
DEFINITION
Iron deficiency anaemia (IDA) is anaemia resulting from inadequate iron for haemoglobin synthesis. It is the commonest nutritional deficiency and the commonest cause of anaemia in children worldwide, and produces a microcytic, hypochromic anaemia.
ETIOLOGY
- Inadequate intake — prolonged exclusive milk feeding, delayed/inadequate complementary feeding, early introduction of cow's milk (low iron + occult GI blood loss).
- Increased demand — infancy, adolescence (growth spurt), prematurity/low birth weight (low iron stores).
- Blood loss — hookworm infestation (important in India), chronic GI bleeding, Meckel's diverticulum, menorrhagia in adolescents.
- Malabsorption — coeliac disease.
PATHOPHYSIOLOGY (stages)
Depletion of iron stores (low ferritin) → Iron-deficient erythropoiesis (low serum iron, high TIBC) → Microcytic, hypochromic anaemia
CLINICAL FEATURES
- Pallor, easy fatigue, poor appetite, irritability and lethargy.
- Pica (eating soil/ice), koilonychia (spoon-shaped nails), glossitis, angular stomatitis.
- Impaired cognition, learning and psychomotor development — an important, sometimes irreversible consequence in young children.
- Reduced exercise tolerance and increased susceptibility to infections.
INVESTIGATIONS
- Haemogram — low haemoglobin with low MCV, MCH, MCHC (microcytic hypochromic) and a raised RDW (anisocytosis).
- Peripheral smear — microcytic hypochromic red cells, pencil cells, target cells.
- Serum ferritin (low) — the best single indicator of iron stores (but rises with infection/inflammation).
- Low serum iron, high total iron-binding capacity (TIBC), low transferrin saturation; raised red-cell distribution width.
💡CLINICAL PEARL: IDA vs thalassaemia trait (both microcytic): IDA has a high RDW, low ferritin and a low-normal RBC count; thalassaemia trait has a normal/high RBC count, normal ferritin and a raised HbA2 — the Mentzer index (MCV/RBC) > 13 favours IDA, < 13 favours thalassaemia.MANAGEMENT
- Oral iron — elemental iron 3–6 mg/kg/day; continue for 2–3 months after the haemoglobin normalises to replenish stores.
- A reticulocytosis in 5–7 days and a rising Hb in 2–4 weeks confirm a response.
- Dietary advice — iron-rich foods (green leafy vegetables, pulses, jaggery, meat), and vitamin-C-containing foods to aid absorption; limit excess cow's milk.
- Treat the cause — deworming for hookworm; investigate for blood loss if the response is poor.
- Parenteral iron or transfusion only for malabsorption, non-adherence or very severe/symptomatic anaemia.
PREVENTION
- Exclusive breastfeeding for 6 months, then timely iron-rich complementary feeding.
- Iron and folic acid supplementation (national Anaemia Mukt Bharat programme) for infants, children, adolescents and pregnant women.
- Periodic deworming; delayed cord clamping at birth; food fortification.
EPIDEMIOLOGY
- The commonest micronutrient deficiency globally; peak risk in infancy (6–24 months) and adolescence.
- Very common in India — targeted by national anaemia-control programmes.
GRADING OF ANAEMIA (WHO)
- Mild, moderate and severe categories by haemoglobin level (age-specific cut-offs).
- Severity guides urgency — severe symptomatic anaemia may need admission/transfusion.
STAGES OF IRON DEPLETION
- Iron depletion — falling ferritin, normal Hb.
- Iron-deficient erythropoiesis — low serum iron, high TIBC, normal Hb.
- Iron deficiency anaemia — the microcytic hypochromic anaemia.
MONITORING THE RESPONSE TO IRON
- Reticulocytosis by day 5–7; a rise in Hb of ~1 g/dL every 2–3 weeks.
- Failure to respond → check adherence, ongoing blood loss, wrong diagnosis (thalassaemia) or malabsorption.
INDICATIONS FOR PARENTERAL IRON / TRANSFUSION
- Parenteral (IV) iron — malabsorption, intolerance of/non-adherence to oral iron, or chronic ongoing loss.
- Blood transfusion — only for very severe, symptomatic anaemia or heart failure (given slowly/in small aliquots).
CONSEQUENCES OF UNTREATED IDA
Beyond anaemia, chronic iron deficiency impairs cognitive development, learning and behaviour (some effects being irreversible), reduces immunity and work/school performance, and in pregnancy increases the risk of low birth weight and prematurity.
📝CLINICAL / APPLIED POINTS- Suspect IDA in any pale, irritable toddler on a milk-heavy diet — it is the commonest paediatric anaemia.
- Ferritin is the best marker of stores but is falsely raised by infection/inflammation (an acute-phase reactant).
- Use the Mentzer index to separate IDA from thalassaemia trait before starting prolonged iron.
- A prompt reticulocyte response confirms the diagnosis and adherence; poor response → wrong diagnosis, non-adherence, or ongoing blood loss.
- Continue iron for 2–3 months AFTER the Hb corrects to refill stores.
🔑KEY POINTS TO REMEMBER- Commonest nutritional anaemia; microcytic hypochromic (low MCV/MCH, high RDW).
- Causes: poor intake, excess cow's milk, increased demand, blood loss (hookworm).
- Low ferritin, low iron, high TIBC; Mentzer index > 13 favours IDA over thalassaemia.
- Oral iron 3–6 mg/kg/day, continued 2–3 months after Hb normalises; treat the cause.
- Prevent with breastfeeding, iron-rich weaning, supplementation and deworming.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics; Anaemia Mukt Bharat guidelines.DEFINITION
Beta-thalassaemia major is an autosomal recessive disorder caused by defective (absent or reduced) synthesis of the beta-globin chains of haemoglobin. The resulting excess alpha chains precipitate in red-cell precursors, causing ineffective erythropoiesis and haemolysis, and a severe transfusion-dependent anaemia.
PATHOPHYSIOLOGY
Absent/reduced β-chain synthesis → Excess α-chains precipitate in RBC precursors → Ineffective erythropoiesis + haemolysis → severe anaemia → Marrow hyperplasia (bone expansion) + extramedullary haematopoiesis → Increased iron absorption + transfusions → iron overload
CLINICAL FEATURES
- Presents from 6 months of age onwards (as protective fetal haemoglobin declines).
- Severe progressive pallor, failure to thrive, lethargy and poor feeding.
- Hepatosplenomegaly (extramedullary haematopoiesis and haemolysis).
- Thalassaemic facies — frontal bossing, maxillary prominence ('chipmunk' face) and skull bossing from marrow expansion.
- Growth retardation and delayed puberty.
INVESTIGATIONS
- Haemogram — severe microcytic hypochromic anaemia.
- Peripheral smear — anisopoikilocytosis, target cells, nucleated RBCs and basophilic stippling.
- Haemoglobin HPLC/electrophoresis — markedly raised HbF, raised HbA2, and reduced/absent HbA (diagnostic).
- X-ray skull — 'hair-on-end' appearance; raised serum ferritin (iron overload); DNA analysis for mutations.
MANAGEMENT
- Regular blood transfusions — 'hypertransfusion' to maintain pre-transfusion Hb ~9–10.5 g/dL (suppresses marrow expansion and allows normal growth).
- Iron chelation therapy — deferasirox/deferiprone (oral) or desferrioxamine (subcutaneous) to prevent and treat transfusional iron overload.
- Folic acid supplementation; splenectomy for hypersplenism/rising transfusion needs (with pre-splenectomy vaccination and penicillin prophylaxis).
- Haematopoietic stem-cell (bone-marrow) transplantation — the only curative option.
COMPLICATIONS
- Iron overload (the major cause of morbidity/mortality) — cardiac (cardiomyopathy, arrhythmia), endocrine (diabetes, hypothyroidism, hypogonadism, growth failure), and liver disease.
- Transfusion-transmitted infections (hepatitis B, C, HIV); alloimmunisation.
- Hypersplenism; gallstones; chronic anaemia effects.
PREVENTION
- Carrier (trait) screening and genetic counselling — especially before marriage/pregnancy.
- Prenatal diagnosis (chorionic villus sampling) in at-risk couples.
- Community awareness and premarital/antenatal screening programmes.
THE THALASSAEMIA SPECTRUM
Type Severity Thalassaemia major Transfusion-dependent, severe Thalassaemia intermedia Moderate, occasional transfusions Thalassaemia minor (trait) Asymptomatic carrier, mild microcytosis TRANSFUSION & MONITORING
- Regular packed-cell transfusions every 2–4 weeks to maintain growth and suppress marrow.
- Monitor serum ferritin and organ iron (cardiac/liver MRI) to guide chelation.
- Screen for endocrine complications, viral infections and alloantibodies.
PSYCHOSOCIAL & SUPPORTIVE CARE
Thalassaemia major is a lifelong, demanding illness; families need counselling, adherence support (chelation is burdensome) and social support, alongside management of complications.
PROGNOSIS
With good transfusion and chelation, survival into adulthood with reasonable quality of life is achievable; poor chelation adherence leads to fatal iron-overload cardiomyopathy. Stem-cell transplantation offers cure in suitable children with a matched donor.
ROLE OF SPLENECTOMY
- Considered for hypersplenism with rising transfusion requirements or symptomatic splenomegaly.
- Requires pre-operative vaccination (pneumococcus, Hib, meningococcus) and lifelong penicillin prophylaxis (post-splenectomy sepsis risk).
COMPLICATIONS BY SYSTEM (iron overload)
- Cardiac — cardiomyopathy and arrhythmia (leading cause of death).
- Endocrine — diabetes, hypothyroidism, hypoparathyroidism, delayed puberty, short stature.
- Hepatic — fibrosis/cirrhosis; and transfusion-transmitted hepatitis.
📝CLINICAL / APPLIED POINTS- A pale infant from ~6 months with hepatosplenomegaly and thalassaemic facies = suspect thalassaemia major.
- HbF is markedly raised on HPLC — the key confirmatory finding.
- The two pillars of care are regular transfusion AND iron chelation — transfusion without chelation kills through iron overload.
- Iron overload damages the heart and endocrine organs — monitor ferritin, cardiac and endocrine function.
- Prevention through carrier screening and genetic counselling is the most cost-effective strategy.
💊KEY DRUG DOSES (viva)- Iron chelation: deferasirox 20–40 mg/kg/day (oral) / desferrioxamine 20–40 mg/kg SC.
- Folic acid 5 mg/day; transfuse to keep pre-transfusion Hb ~9–10.5 g/dL.
🔑KEY POINTS TO REMEMBER- Autosomal recessive defect of β-globin synthesis → ineffective erythropoiesis + haemolysis.
- Presents from 6 months: severe anaemia, hepatosplenomegaly, thalassaemic facies, growth failure.
- HPLC shows markedly raised HbF and HbA2, reduced HbA.
- Treat with regular transfusions + iron chelation; folic acid; transplant is curative.
- Iron overload (heart, endocrine, liver) is the main killer; prevent by carrier screening.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics; thalassaemia management guidelines.DEFINITION
Acute lymphoblastic leukaemia (ALL) is a malignant proliferation of immature lymphoid precursor cells (lymphoblasts) in the bone marrow, which replace normal haematopoiesis. It is the commonest childhood malignancy, with a peak incidence at 2–5 years.
CLINICAL FEATURES
Symptoms arise from bone-marrow failure and tissue infiltration:
- Anaemia — pallor, fatigue, breathlessness.
- Thrombocytopenia — bruising, petechiae, bleeding.
- Neutropenia — fever and recurrent/severe infections.
- Infiltration — bone pain (limp, refusal to walk), generalised lymphadenopathy, hepatosplenomegaly, a mediastinal mass (T-cell ALL), and CNS or testicular involvement.
INVESTIGATIONS
- Haemogram — anaemia, thrombocytopenia, and a variable white-cell count with circulating blasts.
- Peripheral smear — lymphoblasts.
- Bone-marrow examination — diagnostic (> 20–25% blasts); with immunophenotyping (flow cytometry) and cytogenetics/molecular studies for classification and risk.
- CSF examination (CNS involvement); raised LDH and uric acid; baseline biochemistry and imaging.
MANAGEMENT
- Multi-agent chemotherapy in phases — induction (to achieve remission), consolidation/intensification, CNS-directed therapy (intrathecal chemotherapy ± cranial radiation), and maintenance for a total of ~2–3 years.
- Risk stratification (age, WBC count, immunophenotype, cytogenetics, treatment response/MRD) guides intensity.
- Supportive care — transfusions, management of febrile neutropenia (prompt broad-spectrum antibiotics), and prevention/treatment of tumour lysis syndrome (hydration, allopurinol/rasburicase).
- Stem-cell transplant for high-risk/relapsed disease.
⚠️DANGER / REMEMBER: Febrile neutropenia is an oncological emergency — a child on chemotherapy with fever needs urgent assessment and broad-spectrum IV antibiotics without waiting for culture results.PROGNOSIS
The prognosis is very good in children — with modern risk-adapted therapy, long-term cure rates exceed 85%. Favourable factors include age 1–10 years, a low presenting white-cell count, B-cell lineage, favourable cytogenetics and a rapid response to treatment.
CLASSIFICATION
- B-cell precursor ALL — the commonest, generally more favourable.
- T-cell ALL — often older boys, high WBC count and a mediastinal mass.
- Sub-classified further by cytogenetics/molecular markers for risk.
DIFFERENTIAL DIAGNOSIS
- Aplastic anaemia (pancytopenia, no organomegaly), ITP (isolated thrombocytopenia).
- Infections (EBV, whooping cough with lymphocytosis), juvenile arthritis (bone/joint pain), other malignancies (neuroblastoma marrow infiltration).
TUMOUR LYSIS SYNDROME
- Massive tumour breakdown at the start of therapy → hyperkalaemia, hyperphosphataemia, hyperuricaemia, hypocalcaemia and acute kidney injury.
- Prevent with hydration and allopurinol/rasburicase and close biochemical monitoring.
LATE EFFECTS OF THERAPY
- Neurocognitive effects (CNS therapy), endocrine/growth effects, cardiotoxicity (anthracyclines), second malignancies and infertility.
- Long-term survivorship follow-up is important.
PROGNOSTIC FACTORS
Favourable Unfavourable Age 1–10 years < 1 or > 10 years WBC < 50,000 High WBC count B-cell lineage T-cell / infant Favourable cytogenetics Adverse cytogenetics Rapid response / low MRD Slow response / high MRD SANCTUARY SITES & RELAPSE
The CNS and testes are 'sanctuary sites' where chemotherapy penetrates poorly — hence dedicated CNS-directed therapy; relapse at these sites (or in the marrow) is treated with intensified therapy or transplant.
SUPPORTIVE CARE
- Transfusion support; prompt management of febrile neutropenia; infection prophylaxis.
- Nutritional and psychological support; management of chemotherapy side-effects.
EMERGENCIES IN A CHILD WITH LEUKAEMIA
- Febrile neutropenia — urgent broad-spectrum antibiotics.
- Tumour lysis syndrome — hydration + allopurinol/rasburicase.
- Hyperleukocytosis (very high WBC) — risk of leukostasis; mediastinal mass — airway/SVC compression.
📝CLINICAL / APPLIED POINTS- The classic presentation is pallor + bruising + fever + bone pain ± lymphadenopathy/organomegaly.
- Bone marrow with immunophenotyping is diagnostic and essential for risk stratification.
- Bone pain and a limp in a child with cytopenias should raise suspicion of leukaemia.
- Treat febrile neutropenia as an emergency; prevent tumour lysis syndrome at the start of therapy.
- Reassure families that childhood ALL is now highly curable (> 85%).
🔑KEY POINTS TO REMEMBER- Commonest childhood cancer; malignant lymphoblasts replace the marrow; peak 2–5 yr.
- Marrow failure (anaemia, bleeding, infection) + infiltration (bone pain, nodes, organomegaly).
- Bone marrow (> 20–25% blasts) + immunophenotyping is diagnostic.
- Multi-agent chemotherapy in phases (~2–3 yr) with CNS prophylaxis; risk-stratified.
- Febrile neutropenia & tumour lysis are emergencies; cure rate > 85%.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Haemophilia is an X-linked recessive inherited bleeding disorder caused by deficiency of a clotting factor. Haemophilia A (factor VIII deficiency) is the commonest; Haemophilia B (factor IX deficiency, 'Christmas disease') is clinically identical. It affects males, transmitted by carrier females.
SEVERITY (by factor level)
Severity Factor level Bleeding pattern Severe < 1% Spontaneous bleeds (joints, muscles) Moderate 1–5% Bleeding with minor trauma Mild 5–40% Bleeding only with surgery/major trauma CLINICAL FEATURES
- Haemarthrosis — recurrent bleeding into joints (knees, ankles, elbows), causing pain, swelling and, over time, chronic arthropathy and 'target joints'.
- Muscle haematomas and deep soft-tissue bleeds.
- Prolonged bleeding after trauma, surgery, dental extraction or circumcision.
- Intracranial haemorrhage — the most dangerous, life-threatening bleed.
- Bleeding is typically delayed and deep (unlike the immediate, superficial mucocutaneous bleeding of platelet disorders).
INVESTIGATIONS
- Prolonged aPTT (intrinsic pathway) with a normal PT, normal platelet count and normal bleeding time.
- A mixing study corrects the aPTT (factor deficiency) unless an inhibitor is present.
- Specific factor assay (VIII or IX) confirms the diagnosis and grades severity.
- Genetic testing for carrier detection and prenatal diagnosis.
MANAGEMENT
- Factor replacement — factor VIII or IX concentrate, given on-demand for bleeds or as regular prophylaxis in severe disease (to prevent joint damage).
- Desmopressin (DDAVP) — raises factor VIII in mild haemophilia A.
- Antifibrinolytics (tranexamic acid) for mucosal/dental bleeding.
- Acute joint bleed — factor replacement plus RICE (rest, ice, compression, elevation) and analgesia.
- Avoid intramuscular injections, aspirin and NSAIDs; immunise (including hepatitis B); manage inhibitor development.
COMPLICATIONS
- Chronic haemophilic arthropathy (the major long-term morbidity) and joint deformity.
- Inhibitor (antibody) development against the factor — makes bleeds hard to treat.
- Transfusion-transmitted infections (historically); life-threatening intracranial/airway bleeds.
GENETICS & INHERITANCE
- X-linked recessive — affected males, carrier females (who may have mildly low factor levels).
- An affected father cannot transmit to sons, but all his daughters are carriers; a carrier mother transmits to 50% of sons (affected) and 50% of daughters (carriers).
- ~⅓ of cases arise from new mutations (no family history).
DIFFERENTIAL DIAGNOSIS OF A BLEEDING CHILD
Feature Platelet/vWD disorder Haemophilia (factor) Bleeding type Mucocutaneous, petechiae Deep — joints, muscles Onset after injury Immediate Delayed Platelets/PT Abnormal (± PT) Normal aPTT Usually normal Prolonged COMPREHENSIVE CARE
- Care in a haemophilia treatment centre with a multidisciplinary team.
- Home therapy and factor prophylaxis; physiotherapy for joints; genetic counselling and carrier testing.
- Regular review for inhibitors and blood-borne infections.
INHIBITORS
Some patients develop antibodies (inhibitors) against infused factor, which neutralise treatment and make bleeds difficult to control. Suspected when bleeding fails to respond to adequate factor; managed with bypassing agents and immune-tolerance induction.
MANAGEMENT OF BLEEDS BY SITE
- Joint/muscle bleed — factor + RICE + analgesia; avoid aspiration unless necessary.
- Mucosal/dental — factor + tranexamic acid.
- Life-threatening (intracranial, airway, GI) — immediate high-dose factor and urgent assessment.
WHY PROPHYLAXIS?
Regular prophylactic factor in severe haemophilia prevents recurrent joint bleeds and the resulting crippling arthropathy, and is now the standard of care where resources allow.
GENERAL PRECAUTIONS FOR THE FAMILY
- Avoid intramuscular injections, aspirin and NSAIDs; give vaccines subcutaneously with pressure.
- Wear medical-alert identification; seek care early for any significant bleed, especially head injury.
- Encourage safe activity/physiotherapy to protect joints while avoiding high-contact sports.
📝CLINICAL / APPLIED POINTS- Deep bleeding (joints, muscles) that is delayed after trauma is typical of a coagulation-factor disorder like haemophilia.
- Prolonged aPTT with a normal PT and normal platelets points to an intrinsic-pathway factor deficiency.
- Confirm with a specific factor assay; a mixing study distinguishes deficiency from an inhibitor.
- Treat bleeds early with factor; avoid IM injections, aspirin and NSAIDs.
- Prophylactic factor in severe disease prevents the crippling joint arthropathy.
💊KEY DRUG DOSES (viva)- Factor VIII — 1 U/kg raises level by ~2%; factor IX — 1 U/kg raises by ~1%.
- Minor bleed: raise to ~30–50%; major/intracranial: to ~80–100%.
- Desmopressin 0.3 µg/kg (mild haemophilia A); tranexamic acid 10 mg/kg for mucosal bleeds.
🔑KEY POINTS TO REMEMBER- X-linked recessive; Haemophilia A (factor VIII) commonest, B (factor IX); affects males.
- Deep bleeds — haemarthrosis, muscle haematomas, prolonged post-trauma bleeding.
- Prolonged aPTT, normal PT/platelets/bleeding time; factor assay confirms & grades.
- Factor replacement (on-demand or prophylaxis); DDAVP for mild A; avoid IM/aspirin.
- Main complications: chronic arthropathy, inhibitors, intracranial bleed.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics; WFH haemophilia guidelines.DEFINITION
Anaemia is a reduction in the haemoglobin concentration (or red-cell mass) below the normal range for age and sex. Because normal values change with age, an age-appropriate cut-off must be used (e.g. WHO: Hb < 11 g/dL at 6 months–5 years). A systematic approach identifies the cause efficiently.
TWO USEFUL CLASSIFICATIONS
Anaemia can be approached morphologically (by MCV) and kinetically (by mechanism):
MORPHOLOGICAL CLASSIFICATION (by MCV)
Type Examples Microcytic (low MCV) Iron deficiency, thalassaemia, anaemia of chronic disease, sideroblastic Normocytic (normal MCV) Haemolysis, acute blood loss, marrow failure/aplasia, chronic disease Macrocytic (high MCV) Megaloblastic (B12/folate), hypothyroidism, liver disease, aplastic anaemia KINETIC CLASSIFICATION (by mechanism)
- Decreased production — nutritional deficiency, marrow failure/infiltration, chronic disease.
- Increased destruction (haemolysis) — membrane, enzyme (G6PD), haemoglobin (thalassaemia, sickle) defects; immune haemolysis.
- Blood loss — acute or chronic.
THE RETICULOCYTE COUNT (a key discriminator)
- High reticulocyte count → the marrow is responding → haemolysis or blood loss.
- Low reticulocyte count → a production defect (nutritional deficiency, marrow failure).
CLINICAL EVALUATION
- History — diet, pica, blood loss, jaundice, drugs, family history (thalassaemia/haemolysis), age of onset, ethnicity.
- Examination — pallor, jaundice (haemolysis), hepatosplenomegaly and lymphadenopathy (haemolysis, leukaemia), bony changes, petechiae (marrow failure), koilonychia (IDA).
INVESTIGATIONS (stepwise)
- Haemogram with indices (MCV, MCH, RDW) and a peripheral smear — the essential first step.
- Reticulocyte count — to separate production from destruction/loss.
- Targeted tests — iron studies/ferritin (microcytic), HPLC (thalassaemia), B12/folate (macrocytic), Coombs test, G6PD, haemolysis markers (LDH, bilirubin) (haemolytic), and bone marrow (marrow failure/infiltration).
💡CLINICAL PEARL: A practical starting algorithm: MCV → microcytic/normocytic/macrocytic; then the reticulocyte count → high (haemolysis/blood loss) vs low (production defect); then the peripheral smear and targeted tests. This resolves most anaemias quickly.AGE-RELATED NORMAL HAEMOGLOBIN (approx. lower limits)
Age Hb (g/dL) Newborn 14–15 3 months (physiological nadir) ~9.5–11 6 months–5 years ≥ 11 6–12 years ≥ 11.5 Adolescent ≥ 12 (girls) / ≥ 13 (boys) PERIPHERAL SMEAR CLUES
- Microcytic hypochromic + pencil cells → iron deficiency; target cells + basophilic stippling → thalassaemia.
- Macro-ovalocytes + hypersegmented neutrophils → megaloblastic; spherocytes → hereditary spherocytosis/immune haemolysis.
- Sickle cells → sickle disease; bite cells/Heinz bodies → G6PD deficiency; blasts → leukaemia.
PRINCIPLE OF MANAGEMENT
Management is directed at the specific cause identified — nutritional replacement, treatment of haemolysis/blood loss, or referral for marrow disease — rather than empirical transfusion, which is reserved for severe symptomatic anaemia.
MARKERS OF HAEMOLYSIS
- Raised reticulocytes, unconjugated bilirubin and LDH; low haptoglobin.
- A positive direct Coombs test indicates immune haemolysis; blood-film morphology suggests the cause.
WHEN TO REFER
- Pancytopenia, blasts on the smear, or an unexplained non-nutritional anaemia.
- Suspected haemolysis, marrow failure or malignancy — for specialist evaluation and marrow study.
KEY PRINCIPLE
A logical, stepwise use of a few inexpensive tests (haemogram with indices, smear, reticulocyte count) identifies the mechanism in most children before committing to more expensive or invasive investigations.
COMMON CLINICAL PATTERNS (quick recognition)
- Microcytic + low ferritin + high RDW → iron deficiency.
- Microcytic + normal ferritin + raised HbA2 → thalassaemia trait.
- Normocytic + high reticulocytes + jaundice → haemolysis.
- Macrocytic + hypersegmented neutrophils → megaloblastic anaemia.
- Pancytopenia → marrow failure or infiltration (needs marrow study).
📝CLINICAL / APPLIED POINTS- Always use an age-appropriate haemoglobin cut-off — 'normal' changes across childhood.
- The MCV and reticulocyte count together narrow the differential rapidly.
- The peripheral smear is a cheap, high-yield test — never skip it.
- Hepatosplenomegaly/lymphadenopathy or pancytopenia point away from simple nutritional anaemia toward haemolysis or marrow disease.
- A microcytic anaemia not responding to iron — reconsider thalassaemia trait or ongoing blood loss.
🔑KEY POINTS TO REMEMBER- Anaemia = Hb below the age/sex-specific normal.
- Classify morphologically (MCV: micro/normo/macrocytic) and kinetically (production/destruction/loss).
- Reticulocytes: high = haemolysis/blood loss; low = production defect.
- First tests: haemogram with indices + peripheral smear + reticulocyte count.
- Then targeted tests — iron studies, HPLC, B12/folate, Coombs/G6PD, marrow.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Immune (idiopathic) thrombocytopenic purpura (ITP) is an acquired disorder of immune-mediated platelet destruction (antibody-coated platelets removed by the spleen), causing isolated thrombocytopenia. It is the commonest cause of acute thrombocytopenia in a well child.
CLINICAL FEATURES
- Often follows a viral infection 1–3 weeks earlier; typically a well child aged 2–6 years.
- Sudden petechiae, purpura and bruising; mucosal bleeding (epistaxis, gum bleeding).
- No hepatosplenomegaly or lymphadenopathy (their presence suggests another diagnosis, e.g. leukaemia).
INVESTIGATIONS
- Isolated thrombocytopenia with a normal haemoglobin and white-cell count; large (young) platelets on the smear.
- Bone marrow (if atypical) shows normal or increased megakaryocytes.
- It is largely a diagnosis of exclusion.
MANAGEMENT
- Acute childhood ITP is usually self-limiting — most recover within weeks to months.
- Observation for mild disease (skin signs only); avoid trauma, contact sports and antiplatelet drugs.
- For significant bleeding or very low counts — corticosteroids, IV immunoglobulin, or anti-D.
- Chronic ITP (> 12 months) — further options (thrombopoietin agonists, rituximab, splenectomy).
DIFFERENTIAL DIAGNOSIS
- Leukaemia (look for anaemia, neutropenia, blasts, organomegaly), aplastic anaemia.
- Other causes of thrombocytopenia — infections (dengue), drugs, hypersplenism, SLE.
COMPLICATIONS & PROGNOSIS
Serious bleeding (including rare intracranial haemorrhage) is the main risk with very low counts. Most childhood ITP resolves spontaneously within 6–12 months with an excellent prognosis; a minority become chronic.
WHEN TO INVESTIGATE FURTHER / SUSPECT ANOTHER CAUSE
- Abnormal haemoglobin or white cells, organomegaly or lymphadenopathy → bone marrow to exclude leukaemia/aplasia.
- Atypical age, chronic course, or failure to respond to standard therapy.
KEY EXAM POINT
The hallmark is isolated thrombocytopenia in an otherwise well child with a normal examination — a normal haemoglobin and white-cell count and the absence of organomegaly separate ITP from leukaemia.
🔑KEY POINTS TO REMEMBER- Immune platelet destruction → isolated thrombocytopenia in a well child.
- Post-viral; petechiae/purpura/mucosal bleeding; NO organomegaly/lymphadenopathy.
- Isolated low platelets (normal Hb/WBC); marrow shows normal/increased megakaryocytes.
- Usually self-limiting; observe if mild; steroids/IVIG/anti-D for significant bleeding.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Sickle cell disease is an autosomal recessive haemoglobinopathy caused by a point mutation (glutamate → valine at position 6 of the beta-globin chain) producing haemoglobin S (HbS). Under low-oxygen conditions HbS polymerises, deforming red cells into a rigid sickle shape → vaso-occlusion and chronic haemolysis.
CLINICAL FEATURES
- Vaso-occlusive (painful) crises — bone/abdominal pain; dactylitis (painful hand-foot swelling) is often the first sign in infants.
- Acute chest syndrome, stroke, priapism.
- Splenic sequestration and aplastic crisis (parvovirus B19).
- Functional asplenia → susceptibility to encapsulated-organism infection; chronic haemolytic anaemia, jaundice and gallstones.
INVESTIGATIONS
- Sickling test (positive); haemoglobin HPLC/electrophoresis shows HbS (diagnostic).
- Blood film — sickle cells, target cells, Howell-Jolly bodies (hyposplenism).
MANAGEMENT
- Crisis — hydration, analgesia, oxygen, and treatment of any precipitant/infection.
- Preventive — penicillin prophylaxis and vaccination (pneumococcus etc.), folic acid, and hydroxyurea (raises HbF, reduces crises).
- Transfusion for severe complications; stem-cell transplant is curative in selected cases.
TYPES OF CRISES
Crisis Features Vaso-occlusive Pain (bones, abdomen), dactylitis Sequestration Sudden splenic pooling → shock, anaemia Aplastic Parvovirus B19 → marrow shutdown Haemolytic Increased haemolysis, worsening anaemia PROGNOSIS
Prognosis has improved greatly with early diagnosis, penicillin prophylaxis, vaccination and hydroxyurea; complications such as stroke and acute chest syndrome remain important causes of morbidity and mortality.
PRECIPITANTS OF CRISIS
- Infection, dehydration, hypoxia, cold exposure, acidosis and physical/emotional stress.
- Avoiding these — plus good hydration, prompt infection treatment and vaccination — reduces crises.
GENOTYPES
- HbSS (sickle cell anaemia) — homozygous, most severe.
- HbSC disease and HbS/β-thalassaemia — variable severity.
- Sickle cell trait (HbAS) — asymptomatic carrier (protective against malaria).
NEWBORN SCREENING & DIAGNOSIS
Early diagnosis (newborn screening/HPLC) allows penicillin prophylaxis and pneumococcal vaccination from infancy, which markedly reduce early mortality from overwhelming sepsis (functional asplenia).
💊KEY DRUG DOSES (viva)- Penicillin V prophylaxis 125 mg BD (<5 yr) / 250 mg BD; folic acid 5 mg/day.
- Hydroxyurea 15–35 mg/kg/day (reduces crises); analgesia for crises.
🔑KEY POINTS TO REMEMBER- Autosomal recessive HbS; sickling under hypoxia → vaso-occlusion + haemolysis.
- Painful crises, dactylitis, acute chest syndrome, sequestration, functional asplenia.
- HPLC confirms HbS; blood film shows sickle cells + Howell-Jolly bodies.
- Crisis: hydration, analgesia, oxygen; prevent with penicillin, vaccines, folic acid, hydroxyurea.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Megaloblastic anaemia is a macrocytic anaemia caused by deficiency of vitamin B12 or folate, which impairs DNA synthesis. This produces large, immature red-cell precursors (megaloblasts) and ineffective erythropoiesis.
CAUSES
- Vitamin B12 — inadequate intake (strict vegetarian diet; infants breastfed by a B12-deficient mother), malabsorption (pernicious anaemia, ileal disease).
- Folate — poor intake (goat's milk, overcooked food), increased demand (haemolysis, rapid growth), malabsorption, and drugs (methotrexate, phenytoin).
CLINICAL FEATURES
- Pallor, fatigue, glossitis and mild jaundice; skin hyperpigmentation.
- Neurological features with B12 deficiency — developmental regression, irritability, hypotonia in infants (and subacute combined degeneration in older patients).
- Severe cases → pancytopenia.
INVESTIGATIONS & MANAGEMENT
- Macrocytic anaemia (high MCV); blood film — macro-ovalocytes and hypersegmented neutrophils; marrow shows megaloblasts.
- Low serum B12 and/or folate.
- Replace the deficient vitamin — B12 (usually intramuscular) or oral folic acid; treat the underlying cause; correct diet.
DIFFERENTIAL DIAGNOSIS
- Other causes of macrocytosis — hypothyroidism, liver disease, aplastic anaemia, reticulocytosis.
- Combined iron + B12/folate deficiency (a 'dimorphic' picture with a normal MCV).
KEY EXAM POINT
A macrocytic anaemia with hypersegmented neutrophils, especially in a breastfed infant of a vegetarian mother, should prompt B12 assessment — neurological damage from B12 deficiency can be irreversible if treatment is delayed.
COMPLICATIONS & FOLLOW-UP
- Severe deficiency → pancytopenia and (with B12) irreversible neurological damage.
- Monitor the response (reticulocytosis within a week; correction of blood counts) and address the dietary/absorptive cause to prevent recurrence.
KEY EXAM POINT
Combined deficiencies are common — a child may have both iron and B12/folate deficiency, giving a misleadingly normal MCV; the blood film and specific assays clarify the picture.
PREVENTION
Ensure adequate maternal B12/folate in pregnancy and lactation, dietary diversification, and folic-acid supplementation in situations of increased demand (haemolysis, prematurity, rapid growth).
🔑KEY POINTS TO REMEMBER- Macrocytic anaemia from B12 or folate deficiency (impaired DNA synthesis).
- B12: vegetarian diet / breastfed by deficient mother; folate: poor intake, increased demand.
- High MCV, hypersegmented neutrophils, megaloblasts; ± neuro features (B12).
- Replace the deficient vitamin and treat the cause.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Aplastic anaemia is pancytopenia (anaemia + leucopenia + thrombocytopenia) with a hypocellular ('empty') bone marrow, due to failure of the haematopoietic stem cells. There is no abnormal infiltration or organomegaly.
CAUSES
- Acquired — idiopathic (commonest), drugs/toxins (chloramphenicol, chemotherapy, benzene), radiation, viral (hepatitis, EBV), immune-mediated.
- Inherited — Fanconi anaemia (with short stature, café-au-lait spots, radial/thumb anomalies), dyskeratosis congenita.
CLINICAL FEATURES
- Anaemia (pallor, fatigue), thrombocytopenia (bruising, bleeding) and neutropenia (infections).
- No hepatosplenomegaly or lymphadenopathy — an important point distinguishing it from leukaemia.
INVESTIGATIONS & MANAGEMENT
- Pancytopenia with a low reticulocyte count; bone-marrow biopsy shows a hypocellular marrow replaced by fat.
- Supportive care — red-cell and platelet transfusions, prompt treatment of infections.
- Immunosuppression (antithymocyte globulin + cyclosporine) and haematopoietic stem-cell transplantation (curative) for severe disease.
ASSESSING SEVERITY
- Severity graded by the degree of neutropenia, thrombocytopenia and reticulocytopenia.
- Very low neutrophils/platelets/reticulocytes define severe aplastic anaemia — an indication for urgent definitive therapy.
KEY EXAM POINT
Pancytopenia without hepatosplenomegaly or lymphadenopathy suggests aplastic anaemia; the bone-marrow biopsy (hypocellular) distinguishes it from leukaemia (hypercellular with blasts). Always consider inherited Fanconi anaemia in a child with associated anomalies.
COMPLICATIONS
- Life-threatening infection (neutropenia) and haemorrhage (thrombocytopenia).
- Iron overload from repeated transfusions; and, in inherited forms, a risk of evolving into leukaemia.
PROGNOSIS
Severe aplastic anaemia is life-threatening without treatment; outcomes have improved greatly with early stem-cell transplantation (best in young patients with a matched sibling donor) or immunosuppressive therapy.
DIFFERENTIAL DIAGNOSIS
- Leukaemia (hypercellular marrow with blasts), marrow infiltration, and hypersplenism.
- Megaloblastic anaemia and overwhelming infection can also cause pancytopenia.
🔑KEY POINTS TO REMEMBER- Pancytopenia + hypocellular marrow (stem-cell failure); no organomegaly.
- Causes: idiopathic, drugs/toxins, radiation, viral; inherited (Fanconi anaemia).
- Anaemia + bleeding + infections; low reticulocytes; marrow biopsy is key.
- Supportive care + immunosuppression; transplant is curative.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzyme disorder (affecting males) that leaves red cells vulnerable to oxidative stress, causing episodic acute haemolysis. It is the commonest human enzyme defect.
PRECIPITANTS (oxidative triggers)
- Infections (the commonest trigger).
- Drugs — antimalarials (primaquine), sulfonamides, nitrofurantoin, dapsone.
- Fava beans (favism); naphthalene (mothballs).
CLINICAL FEATURES
- Acute haemolysis 1–3 days after a trigger — pallor, jaundice, dark (cola-coloured) urine, and abdominal/back pain.
- Neonatal jaundice (an important cause in some populations).
- Usually well between episodes.
INVESTIGATIONS & MANAGEMENT
- Blood film during haemolysis — 'bite' cells and Heinz bodies; features of haemolysis.
- G6PD enzyme assay (measure a few weeks after the acute episode, as young reticulocytes have higher enzyme levels and can give a false-normal result).
- Avoid the triggers; supportive care and hydration; blood transfusion for severe haemolysis.
PATHOPHYSIOLOGY
G6PD generates NADPH, which protects red cells against oxidative damage. When enzyme activity is low, oxidative stress denatures haemoglobin (forming Heinz bodies), and the spleen removes the damaged cells ('bite cells'), causing acute haemolysis.
KEY EXAM POINT
Ask about a recent infection, drug or fava-bean ingestion in a child with sudden pallor, jaundice and dark urine; confirm with an enzyme assay weeks after the acute episode (a test done during haemolysis can be falsely normal).
CLASSES OF SEVERITY
- The WHO classifies G6PD variants by residual enzyme activity — from severe chronic haemolysis to mild, episodic disease.
- Most affected children have the milder, episodic form triggered by oxidative stress.
MANAGEMENT SUMMARY
- The mainstay is avoidance of oxidative triggers (educate the family, provide a drug list).
- Supportive care during a haemolytic episode; transfusion only if anaemia is severe; treat neonatal jaundice (phototherapy/exchange).
🔑KEY POINTS TO REMEMBER- X-linked enzyme defect → oxidative haemolysis (affects males).
- Triggers: infections, drugs (antimalarials, sulfa), fava beans, mothballs.
- Acute haemolysis (pallor, jaundice, dark urine) after a trigger; neonatal jaundice.
- Bite cells & Heinz bodies; enzyme assay (delay after acute episode); avoid triggers.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Neuroblastoma is an embryonal malignancy arising from neural crest cells of the sympathetic nervous system (adrenal medulla or sympathetic chain). It is the commonest extracranial solid tumour of childhood and usually occurs in children under 5 years.
CLINICAL FEATURES
- An abdominal mass that is often irregular and crosses the midline (contrast with Wilms tumour); commonly arises from the adrenal.
- Features of metastatic disease — bone pain, periorbital bruising ('raccoon eyes') and proptosis, bone-marrow involvement, hepatomegaly.
- Catecholamine effects (hypertension, sweating, flushing) and paraneoplastic opsoclonus-myoclonus ('dancing eyes').
INVESTIGATIONS & MANAGEMENT
- Raised urinary catecholamine metabolites (VMA and HVA).
- Imaging (USG/CT/MRI), MIBG scan, and tissue biopsy (with MYCN amplification status for risk).
- Risk-based treatment — surgery, chemotherapy and radiotherapy; prognosis varies widely (infants often do well, and some tumours spontaneously regress, while high-risk disease has a poorer outcome).
WILMS TUMOUR vs NEUROBLASTOMA
Feature Neuroblastoma Wilms tumour Origin Sympathetic chain/adrenal Kidney Mass Irregular, crosses midline Smooth, doesn't cross midline Markers Urinary VMA/HVA — Child Often ill, metastatic Usually well PROGNOSIS
Outcome depends on age, stage and biology (MYCN amplification) — infants and localised tumours do well (some regress spontaneously), whereas high-risk metastatic disease in older children has a poorer prognosis.
STAGING & SPECIAL FEATURES
- Staged by the extent of disease and resectability, and risk-grouped using age and MYCN status.
- Stage 4S (special, in infants) — disseminated but with a good prognosis and a tendency to spontaneous regression.
KEY EXAM POINT
An irregular abdominal mass that crosses the midline with raised urinary VMA/HVA points to neuroblastoma (vs Wilms tumour, which is smooth and does not cross the midline); metastatic signs such as 'raccoon eyes' are characteristic.
BIOLOGICAL / PROGNOSTIC MARKERS
- MYCN amplification — the key adverse prognostic marker (high-risk disease).
- Age (< 18 months favourable), stage, histology (Shimada) and DNA ploidy also stratify risk.
- Raised urinary VMA/HVA and serum ferritin/LDH/NSE support diagnosis and monitoring.
🔑KEY POINTS TO REMEMBER- Commonest extracranial solid tumour of childhood; neural crest origin; age < 5 yr.
- Abdominal mass that CROSSES the midline; metastases → 'raccoon eyes', bone pain.
- Raised urinary VMA/HVA; MIBG scan; MYCN status guides risk.
- Risk-based surgery/chemo/radiotherapy; infants may spontaneously regress.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics.DEFINITION
Hodgkin lymphoma (HL) is a malignant lymphoma arising in lymph nodes, characterised by the presence of the diagnostic Reed-Sternberg (RS) cell — a large binucleate cell with prominent eosinophilic nucleoli giving an 'owl-eye' appearance — surrounded by a reactive inflammatory background. It shows a bimodal age distribution (adolescents/young adults and older adults).
HISTOLOGICAL CLASSIFICATION (WHO)
Two broad groups — Classical HL (~95%) (RS cells are CD15+ and CD30+) and Nodular lymphocyte-predominant HL:
Subtype Key features Nodular sclerosis Commonest (~70%); adolescents; mediastinal mass; lacunar cells Mixed cellularity 2nd commonest; EBV-associated; older/immunocompromised Lymphocyte-rich Few RS cells; good prognosis Lymphocyte-depleted Many RS cells; worst prognosis; HIV-associated Nodular lymphocyte-predominant 'Popcorn' (L&H) cells, CD20+; indolent, late relapses ETIOLOGY & RISK FACTORS
- Epstein-Barr virus (EBV) — strongly linked to mixed-cellularity HL.
- Immunodeficiency (HIV), immunosuppression; family history.
CLINICAL FEATURES
- Painless, firm, rubbery lymphadenopathy — most often cervical/supraclavicular; spreads in a contiguous (predictable, node-to-adjacent-node) fashion.
- Mediastinal mass — cough, dyspnoea, or superior vena cava obstruction.
- 'B symptoms' — fever > 38 °C, drenching night sweats, and weight loss > 10% over 6 months (indicate a worse prognosis).
- Classical clues — Pel-Ebstein (cyclical) fever, alcohol-induced nodal pain, and generalised pruritus.
- Hepatosplenomegaly and, in advanced disease, marrow involvement.
INVESTIGATIONS
- Excisional lymph-node biopsy — the diagnostic test; demonstrates Reed-Sternberg cells with immunophenotyping (CD15/CD30).
- CBC (anaemia), ESR and LDH (raised; prognostic), renal/liver function.
- Contrast CT (neck, chest, abdomen, pelvis) and PET-CT for staging; chest X-ray for a mediastinal mass.
- Bone-marrow biopsy for advanced-stage/B-symptom disease.
ANN ARBOR STAGING (with Cotswold modification)
Stage Extent I A single lymph-node region II ≥ 2 regions on the same side of the diaphragm III Regions on both sides of the diaphragm (± spleen) IV Diffuse extranodal spread (liver, marrow, lung) Suffixes: A (no B symptoms), B (B symptoms present), E (extranodal extension), S (splenic), X (bulky disease).
HODGKIN vs NON-HODGKIN LYMPHOMA (high-yield comparison)
Feature Hodgkin lymphoma Non-Hodgkin lymphoma Cell Reed-Sternberg cell No RS cell Spread Contiguous (orderly) Non-contiguous ('skip' lesions) Extranodal disease Uncommon Common Site Usually cervical/mediastinal Often abdominal / widespread Presentation Nodal, B symptoms May be an emergency (mass, tumour lysis) Prognosis Excellent Variable MANAGEMENT
- Risk-adapted chemotherapy — the standard regimen is ABVD (Adriamycin/doxorubicin, Bleomycin, Vinblastine, Dacarbazine), with the number of cycles guided by stage and PET response.
- Involved-field/site radiotherapy is added for bulky or residual disease (used cautiously in children to limit late effects).
- Treatment intensity is tailored (de-escalated for PET-negative early disease).
PROGNOSIS & LATE EFFECTS
- Excellent prognosis — cure rates > 90% in early-stage childhood HL.
- Late effects of therapy — second malignancies, anthracycline cardiotoxicity, bleomycin lung toxicity, hypothyroidism (neck radiation) and infertility — hence long-term survivorship follow-up.
🔑KEY POINTS TO REMEMBER- Malignant lymphoma with diagnostic Reed-Sternberg (owl-eye, CD15+/CD30+) cells.
- Classical HL: nodular sclerosis (commonest), mixed cellularity (EBV), lymphocyte-rich, lymphocyte-depleted (worst); + NLPHL (CD20+).
- Painless contiguous cervical lymphadenopathy ± mediastinal mass + B symptoms.
- Excisional biopsy is diagnostic; stage by Ann Arbor (A/B, E, S, X); PET-CT.
- Treat with ABVD chemotherapy ± radiotherapy; > 90% cure; watch late effects.
📚SOURCES: Ghai Essential Pediatrics; Nelson Textbook of Pediatrics; WHO lymphoma classification.