Important Hematological Disorders In Children

Hematological disorders in children can be complex to diagnose and manage, and require a thorough understanding of the pathophysiology, clinical presentation, and appropriate treatment options.

Read this blog further to know more about the important hematological disorders in children and strengthen your pediatrics preparations for NExT/NEET PG exam.

Normal Erythropoiesis      

• Normal human haemoglobins

	Hemoglobin	Structural formula
Embryonic	Hb-Gower 1	ζ2ε2
	HB-Gower 2	α2 ε 2
	Hb- Portland	ζ2γ2
Fetal	Hb-F	α2γ2 (0.5-1%)
Adult	Hb-A	α2β2 (97%)
	Hb- A2	α2 δ2  (1.5-3.2%)

 Major Sites Of Hematopoiesis              

• Yolk sac: Starts from 3^rd week till 10-12^th week
• Liver: Starts at 6-8^th week, ceases by 2^nd trimester
• Bone marrow: Starts from 2^nd trimester onwards

Anemias In Children  

• WHO definition
  • Children 6 months – 5 years: Hb < 11 g/dl
  • Children 6-14 years: Hb < 12 g/dl
• Approach to anemia in children

 

Pallor, lethargy
Hepatosplenomegaly
Absent		Present
No Petechiae Iron deficiency anemia Megaloblastic Anemia Pure red cell aplasia  Lead poisoning Chronic kidney disease	Petechiae Present       Aplastic Anemia Bleeding disease Coagulation disease DIC		Lymphadenopathy
			Absent Thalassemia Sickle cell disease	Present Leukemia Infection Infiltrative Disorders

Iron Deficiency Anemia         

• Mc cause of nutritional disorder in the world
• MC cause of anemia in the world

Etiology 

• Decreased iron intake 
  • Inadequate diet
• Impaired absorption: Celiac disease
• Increased iron loss
  • Gastrointestinal bleeding
  • Inflammatory bowel disease
• Increased requirements
  • infancy, puberty
• Inadequate presentation to erythroid precursors
  • Atransferrinemia

Clinical Features 

• Pallor: generalised weakness, lethargy
• Smooth and shiny tongue
• Pica
• Koilonychia
• PS: Microcytic, Hypochromic Anaemia, anisocytosis, target cells, pencil cells

D/D of microcytic, hypochromic anemia	IDA	B Thalassemia minor / trait	Anaemia of Chronic disease
RDW	Increased	Normal	Normal/Increased
S. iron	Decreased	Normal/Increased	Decreased
S. ferritin	Decreased	Normal/Increased	Increased
TIBC	Increased	Normal	Decreased
Mentzer Index	>14	<13

Treatment of IDA                                 

• 3-6 mg/kg/ day of elemental iron 
• Maximum dose: 200mg of elemental Iron daily 
• Only 10% of oral dose gets absorbed
• For IV correction, total amount of Iron needed
  = (body weight 2.3) + 500mg

Response to treatment in iron deficiency anemia          

Time after Iron administration	Response
12-24 hours	Decreased irritability, increased appetite
48-72 hours	Reticulocytosis appears, peaks at 5-7 days post treatment
4-30 days	Increase in Hb level (best measure)
1-3 months	Repletion of stores

Megaloblastic Anaemia     

• Due to Vit B12 or folic acid deficiency
• On Peripheral smear: Macro ovalocytes, Hyper segmented neutrophils(>5 lobes in 5% neutrophils)
• Treatment: Vitamin B12 and Folic acid

Βeta-Thalassemia  

• Defect: Decreased production of Beta globin chains.
• Common Mutations in India
  • IVS 1-5 G → C
  • IVS  1-1 G → T
  • Codon 41/42
  • Codon 819
  • 619 by deletion

• Classification
  • Thalassemia trait/ minor: Heterozygous state, Mild Anemia (HbA₂≥ 3.5%, HbF is normal)
  • Thalassemia intermediate (β⁰/β⁺): Moderate anaemia, Hepatosplenomegaly: HbF elevated
  • Thalassemia major (β⁰/β⁰): severe anaemia, hemolytic facies: HbF markedly elevated regular transfusions requirement

Clinical features

• Haemolytic Facies
  • Frontal prominence
  • depressed bridge of nose
  • maxillary prominence
• Hepatosplenomegaly (d/t extramedullary hematopoiesis)

Investigation

• Lat. X Ray skull: ‘Hair on End’ or ‘Crew Cut appearance’

• Hemolytic anemia
  • Low Hb, low MCV, low MCH(thalassemia major)
  • Increased LDH
  • Increased unconjugated bilirubin
• PS: microcytic, hypochromic anemia, target cells, Howel jolly bodies, poikilocytosis
• Osmolar fragility: decreased (NESTROFT- Naked Eye Single Tube Red Cell Osmotic Fragility Test)  
• Coombs test -ve (+ve in immune hemolytic anemias) 
• Hb HPLC(high performance liquid chromatography) or Hb electrophoresis: 
  • beta thalassemia major
    • Hb A decreased
    • Hb A2 increased
    • HbF increased 
• Definitive diagnosis: globin gene mutation- helps in prenatal diagnosis in next pregnancy

Treatment of Thalassemia

• Repeated Blood Transfusions: To maintain pretransfusion Hb level between 9.5-10.5 g/dL
• The only curative treatment for thalassemia major: Hematopoietic stem cell transplantation (HSCT)
• Iron Chelation Therapy: Usually started when serum ferritin >1000 ng/ml
  • Deferoxamine: Parenterally (IV or SC) 
    • Effective in reverting hepatic & cardiac iron deposition.
  • Deferiprone: 1^st oral chelator.
    • Adverse effects ? Agranulocytosis, GI side effects, arthritis
  • Deferasirox:  Oral drug, Effective in decreasing cardiac iron burden & lowering serum ferritin.

Complications of thalassemia and its therapy          

• Endocrine: Osteoporosis, Short stature, delayed puberty, Hypothyroidism, Hypogonadism, D.M
• Cardiac: Heart failure, pericardial effusion, DCM
• GI: Transaminitis
• Other- Infections, allergies

Alpha Thalassemia  

• Normal                           α α/αα
• Alpha trait                        -α/αα
• Alpha thalassemia             --/αα                         
• Non immune hydrops      --/-α
• Free beta and gamma chains: β4 & λ4 (tetramers) – precipitate in RBCs and hemolysis occurs

Sickle Cell Anemia             

• MC Structural Hemoglobinopathy 
• Point mutation in 6^th codon of β-globin gene so there is replacement of glutamate with valine
• Production of Hb with abnormal physiochemical properties that promotes polymerization of deoxygenated Hb
• Heterozygous Trait: sickle cell trait –protects against falciparum
• Homozygous Trait: sickle cell disease
• Pathophysiology 

On Deoxygenation, HbS forms long polymers

↓

RBC membrane damage

Microvascular obstruction leading to ischemia & tissue damage.

Hemolysis in Reticuloendothelial system

• Clinical Features
  • Usually presents after 6 months of age
  • Anemia: pallor, generalized weakness
  • CNS: stroke
  • Retinopathy
  • Hand foot syndrome (dactylitis of hands & foot)
  • Priapism (in 45% of affected male) & erectile dysfunction
  • Auto splenectomy due to splenic infarcts: predisposes to infection by encapsulated organisms
  • Renal papillary necrosis

• Diagnosis
  • PS: evidence of hemolysis, sickle cells, Howel Jolly bodies
  • (SICKLING TEST: mixing a blood sample with metabisulfite or dithionite induces sickling of RBCs, if HbS is present)
  • Spleen biopsy:  Gamma Gandy bodies
  • Hb Electrophoresis to detect HbS peak 
  • Confirmatory test: genetic defect checked 
  • Treatment
• Maintain hydration 
  • Avoid infections & do immunisation
  • Acute painful crisis: analgesia
  • blood transfusion
  • Hydroxyurea for patients with severe symptoms (increases HbF levels)
  • Bone marrow transplantation
  • gene therapy

Fanconi Anemia                       

• AR inheritance
• Abnormal chromosomal fragility (demonstrated using Diepoxybutane or Mitomycin C) 
• Clinical Features
  • Most common Hyperpigmentation, café au lait spots
  • Short stature
  • Absent radius, hypoplastic thumb.
  • Facial dysmorphism: Microcephaly, small eyes, epicanthic folds, abnormal ears.
  • Renal/ CNS/GIT malformations
• Complications: Increased risk of tumors like squamous cell Carcinoma of Head/ Neck/Esophagus.
• Treatment
  • Transfusions
  • HSCT (definitive treatment)

APLASTIC ANEMIA

• Inherited/acquired condition with pancytopenia with hypo/acellular bone marrow
• Clinical features
  • pancytopenia
    • Anemia:pallor, easy fatigability,
    • Thrombocytopenia: bleeding manifestations 
    • Leukopenia: fever, recurrent infections
  • No lymphadenopathy
  • No hepatosplenomegaly
• Diagnosis
  • CBC: pancytopenia
  • PS: normocytic, macrocytic, decreased platelets, decreased WBCs
  • Bone marrow: fat globules
• Treatment 
  • Treat the cause
  • Steroids
  • Immunosuppressants
  • Antithymocyte globulin
  • Transfusion
  • Hsct

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