Paediatrics Marrow Pg 231-240 (Hematology)

Rheumatic Disorders of Childhood

• Intravenous immunoglobulin (IVIG) is the preferred treatment for rheumatic disorders in children.
• The recommended dosage is 2 g/kg.
• IVIG reduces the risk of coronary abnormalities to 2-3%.
• Aspirin is used as an anti-inflammatory medication at a dose of 75 mg/kg until the child is afebrile for 48 hours.
• An anti-platelet dose of 3-5 mg/kg is administered for 6-8 weeks.
• An echocardiogram is performed to assess the heart's condition.
• If the echocardiogram is normal, aspirin is stopped.
• If the echocardiogram is abnormal, aspirin is continued long-term.

Anemia Work-up

• Normal:
  • Peripheral smear findings may reveal hypochromia and microcytosis.
• Pancytopenia:
  • Bone marrow failure: Aplastic anemia.
  • Megaloblastic anemia.
  • Pure red cell aplasia (Diamond-Blackfan syndrome).
• Hemolytic anemia:
  • Aplastic crisis (Parvovirus B19).
  • Autoimmune hemolytic anemia.
• Acute blood loss:

Iron Deficiency Anemia (IDA)

• Iron stores are decreased in IDA.
• IDA leads to decreased erythropoiesis and anemia.
• Iron stores decline after a few months of inadequate iron intake.
• Predisposing factors include decreased dietary iron intake, increased demand (growth spurts), malabsorption (e.g., celiac disease), blood loss, and worm infestation.
• Onset of IDA is typically between 9-24 months.
• Late onset IDA can occur due to good iron stores from the mother.
• Atransferrinemia and transferrin receptor antibodies are rare causes.

Focused Physical Examination

• Universal feature: Pallor.
• Associated congenital defects:
  • Skeletal defects (absent radius/thumb): Observed in Fanconi anemia (bone marrow failure).
• Petechiae/purpura (thrombocytopenia): Seen in leukemia, aplastic anemia, and hemolytic uremic syndrome (acute onset).
• Splenomegaly: Seen in hemolytic anemia and leukemia.
• Generalized lymphadenopathy: Associated with leukemia.

Investigations

• Low MCV: Suggestive of microcytic anemia.
  • Iron Deficiency Anemia (IDA): Most common cause.
  • Anemia of chronic disease/inflammation (ACD/ ACI).
  • Thalassemia.
• Normal MCV: Indicative of normocytic anemia.
• High MCV: Associated with macrocytic anemia.
• Low MCV Anemia:
  • History and findings suggestive of IDA warrant a therapeutic iron trial.
  • Assess the response to iron therapy.
  • If positive response, treat as IDA.
  • Serum ferritin:
    • Low: IDA.
    • Normal: Thalassemias.
    • High: ACD/ACI.
• Normal/High MCV Anemia:
  • Further evaluation based on reticulocyte count (normal: 1-2%).
  • Corrected reticulocyte count provides information on bone marrow response.

  • 2% indicates adequate bone marrow response.

Clinical Features of Iron Deficiency Anemia

• Clinical features:
  • Tiredness.
  • Easy fatigability.
  • Pallor (oral mucosa, nail beds, palpebral conjunctiva).
  • Koilonychia (spooning of nails).
  • Platynychia (flat nails).
  • Atrophic glossitis (shiny, smooth tongue).
  • Associations: pica, temper tantrums, breath-holding spells, restless leg syndrome.

Investigations for Iron Deficiency Anemia

• Peripheral smear:
  • Blood parameters: Low MCV and serum ferritin.

Treatment of Iron Deficiency Anemia

• Ferrous Sulphate:
  • Most effective and economical form of iron.
  • 20% elemental iron is present.
  • Dose: 3-6 mg/kg/day (maximum 200 mg/day).
  • Duration: 4-6 months (to replenish iron stores).

Response to Iron Therapy

Supplementary Therapy

• Dietary modification: Consumption of iron-rich foods.
• Deworming: Albendazole.

Peripheral Smear Findings in IDA

• Hypochromia (pallor 1/3 of cell).
• Microcytosis.
• Anisopoikilocytosis (varying size and shape).

Kawasaki Disease

• The most common childhood vasculitis in India.
• Typically affects children under 5 years old.
• Etiology is idiopathic.

Kawasaki Disease Stages and Clinical Manifestations:

Diagnostic Criteria (Clinical)

• Fever ≥ 5 days
• 4 out of 5 CREAM findings (Conjunctivitis, Rash, Erythema of extremities, Mucocutaneous involvement, Lymphadenopathy)

Investigations for Kawasaki Disease

1. Blood count: Platelet count
   • Normal: Acute phase
   • Increased: Subacute phase
2. Inflammatory markers:
   • ↑ CRP
   • ↑ ESR
3. Echocardiography
   • Normal
   • Frequent evaluation during the second week of illness
   • Evaluate after 1 year

Atypical/Incomplete Kawasaki Disease

• Fever ≥ 5 days + 2/3 CREAM features
• OR Infant with fever ≥ 7 days & no other manifestations
• ESR ≥ 40 mm/hr
• CRP ≥ 3 mg/dL
• Echocardiography → Cardiac involvement seen*
• Treat as Kawasaki Disease*

Prognosis of Kawasaki Disease

• Good prognosis.
• Long-term follow-up required if renal involvement.

Treatment of Kawasaki Disease

• Supportive treatment (self-limiting).
• Steroids: Severe GI involvement.
• 10-20% have recurrence.

Congenital Hemolytic Anemia - Hereditary Spherocytosis

• Inheritance: Autosomal dominant.
• Pathogenesis:
  • Defect in RBC cytoskeletal protein.
  • Spherical RBCs.
  • Reduced deformability.
  • Entrapment in splenic microcirculation.
  • Hemolysis (destruction of RBCs).
  • Splenomegaly (enlarged spleen).

Clinical Features of Hereditary Spherocytosis

• Clinical features:
  • Variable onset of anemia and jaundice (increased RBC lysis).
  • 50% cases show neonatal jaundice.
  • Splenomegaly.
  • Family history often present.
  • Pigment gallstones (increased bilirubin production).
  • Aplastic crisis (acute presentation).
  • Parvovirus B19 infection may occur in patients with hereditary spherocytosis.
  • Bone marrow dysfunction.
  • Pancytopenia.

Other Forms of Congenital Hemolytic Anemia

• Defects of red cell membrane: Hereditary spherocytosis.
• Disorders of red cell metabolism: Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Hemoglobinopathies: Sickle cell anemia and thalassemia.

Megaloblastic Anemia

• Causes:*
• Pure vegetarian/vegan diet.
• Pernicious anemia (auto-antibodies against intrinsic factor).
• Vitamin B12 malabsorption (terminal ileum).
• Inborn errors of metabolism:
  • Homocystinuria.
  • Orotic aciduria.
  • Methylmalonic acidemia.
• Predisposing Factors:*
• Vitamin B12: Deficiency
• Folic acid (FA):
  • Diet: Increased goat milk consumption.
  • Infection: Giardiasis.
  • Drugs: Interference with FA utilization (e.g., 6-mercaptopurine, methotrexate).

Clinical Features of Megaloblastic Anemia

• Clinical features:
  • Pallor, tiredness, and easy fatigability.
  • Characteristic features:
    • Beefy red tongue.
    • Hepatosplenomegaly (in 30-40% of cases).
    • Knuckle hyperpigmentation.

Neurological Manifestations of Megaloblastic Anemia

• Seen in vitamin B12 deficiency due to decreased methylation reactions in the nervous system.
• Can occur before the onset of anemia.
• Features:
  • Loss of position/vibration sense (earliest symptom).
  • Ataxia (unsteadiness of gait).
  • Paresthesia.
  • Peripheral neuropathy.
  • Subacute combined degeneration (SACD) of the spinal cord.

Investigations for Megaloblastic Anemia

• Peripheral smear:
  • Macro-ovalocytes (large, oval RBCs).
  • Hypersegmented neutrophils: At least one neutrophil with ≥ 6 lobes on ≥5% of neutrophils.
  • Delayed nuclear maturation.