Summary of "CCH Session 2 - CLINICAL APPROACH TO ANEMIA IN CHILDREN 28th May '23 IAP Delhi Hematology"

Summary of “CCH Session 2 - Clinical Approach to Anemia in Children”

28th May 2023, IAP Delhi Hematology

Main Ideas and Concepts

1. Classification and Causes of Anemia in Children

Anemias in children can be broadly classified based on underlying defects:

Nuclear maturation defects: Examples include megaloblastic anemia caused by folic acid or vitamin B12 deficiency.
Defects in hemoglobin synthesis: Includes thalassemia syndromes (decreased globin chain production) and structural hemoglobin mutants such as HbSC.
Red cell membrane defects: Examples are hereditary spherocytosis and elliptocytosis.
Increased RBC destruction (Hemolytic anemia): Causes include antibody-mediated (autoimmune hemolytic anemia), mechanical injury (e.g., artificial heart valves), thermal injury, and infections.
Size-based classification of anemia:
- Normocytic (normal-sized RBCs)
- Microcytic (small RBCs) — common in iron deficiency and thalassemia
- Macrocytic (large RBCs) — common in B12/folate deficiency and megaloblastic anemia

2. Laboratory Interpretation and Diagnostic Clues

RDW (Red cell distribution width):
- Elevated in nutritional anemias (iron, B12, folate deficiencies)
- Normal in thalassemia trait
MCV (Mean corpuscular volume):
- Low in microcytic anemia
- High in macrocytic anemia
Differentiating iron deficiency anemia (IDA) from thalassemia trait:
- IDA: Proportional fall in hemoglobin, RBC count, and MCV
- Thalassemia trait: Disproportionate fall in hemoglobin compared to MCV; RBC count is elevated
Chronic disease anemia: Often starts as normocytic normochromic and may progress to microcytic anemia.

3. Pathophysiology Highlights

Iron is essential for heme synthesis; defects in protoporphyrin metabolism cause sideroblastic anemia.
Globin gene defects lead to thalassemia syndromes.
Macrocytosis results from defective DNA synthesis (B12/folate deficiency), causing enlarged RBCs and hyperlobulated neutrophils.
Reticulocytosis indicates hemolysis or marrow response; reticulocytes are larger than mature RBCs and can elevate MCV.

4. Hemolytic Anemia

Classification:
- Hereditary (intracorpuscular defects): membrane defects (e.g., spherocytosis), enzyme defects (e.g., G6PD deficiency), hemoglobinopathies
- Acquired (extracorpuscular defects): autoimmune hemolytic anemia, mechanical destruction, infections
Clinical features: Jaundice, splenomegaly; anemia severity depends on rate of RBC destruction versus marrow compensation.
Diagnostic markers: Reticulocytosis, elevated LDH, unconjugated hyperbilirubinemia, decreased haptoglobin.
Intravascular vs extravascular hemolysis:
- Intravascular causes include microangiopathic hemolytic anemia and infections.
- Extravascular hemolysis involves spleen/liver macrophage destruction.

5. Investigations

Complete blood count (CBC) with reticulocyte count
Peripheral blood smear
Direct antiglobulin test (Coombs test)
Biochemical tests: bilirubin (especially indirect), LDH, haptoglobin
Specific tests:
- G6PD assay
- Osmotic fragility test
- EMA test for hereditary spherocytosis
- Ham’s test and flow cytometry for paroxysmal nocturnal hemoglobinuria (PNH)
Bone marrow aspiration/biopsy in suspected marrow failure (aplastic anemia, leukemia, congenital marrow failure syndromes)
Viral serologies and renal function tests as needed

6. Clinical Approach and History Taking

Detailed history including family history and age of onset
Clinical examination of patient and family members
Look for signs of hemolysis (jaundice, splenomegaly), nutritional deficiencies, and chronic diseases
Consider systemic diseases (renal failure, leukemia, autoimmune disorders) in normocytic anemia

7. Case Discussions

Case 1: 7-year-old boy with chronic jaundice, mild anemia, splenomegaly, indirect hyperbilirubinemia, high MCHC → likely hereditary spherocytosis.
Case 2: 2-month-old infant with macrocytic anemia, low reticulocyte count, bone marrow showing erythroid hypoplasia → diagnosed as Diamond-Blackfan anemia (DBA).
Case 3: 17-year-old girl with microcytic hypochromic anemia, iron refractory anemia confirmed by genetic testing (TMPRSS6 mutation).
Case 4: 3-year-old boy with severe anemia, macrocytosis, repeated transfusions, bone marrow suppression → possible thalassemia intermedia with marrow stress or aplastic crisis.

8. Special Topics

Iron refractory iron deficiency anemia (IRIDA): diagnosis after ruling out other causes; has a genetic basis.
Importance of differentiating iron deficiency anemia from thalassemia trait using lab parameters and HPLC.
Effect of blood transfusion on lab parameters (e.g., B12/folate levels).
Macrocytosis can occur in hemolytic anemia due to increased reticulocytes and folate deficiency.
Persistent hyperbilirubinemia >3-4 mg/dL in hemolytic anemia should prompt evaluation for other causes like Gilbert’s syndrome.

9. Q&A Highlights

Differentiation between iron deficiency anemia and thalassemia trait.
Causes of macrocytosis beyond megaloblastic anemia.
Approach to anemia with low reticulocyte count.
Management challenges in thalassemia patients with poor hemoglobin response.
Role of detailed family and clinical history in diagnosis.

Methodology / Diagnostic Approach

Clinical Evaluation
- Detailed patient history: age at onset, family history, symptoms (jaundice, fatigue, pallor)
- Clinical examination: pallor, jaundice, hepatosplenomegaly, skeletal abnormalities
Initial Laboratory Investigations
- Complete blood count (CBC) including RBC indices (MCV, MCHC, RDW)
- Reticulocyte count (corrected for anemia severity)
- Peripheral blood smear examination
Classify Anemia by RBC Size
- Microcytic anemia: consider iron deficiency, thalassemia trait, chronic disease
- Normocytic anemia: consider anemia of chronic disease, marrow failure, hemolysis
- Macrocytic anemia: consider B12/folate deficiency, marrow disorders
Evaluate for Hemolysis (if suspected)
- Reticulocytosis
- Indirect hyperbilirubinemia
- Elevated LDH
- Decreased haptoglobin
- Urine hemoglobin/hemosiderin
- Direct antiglobulin test (Coombs test)
Specific Tests Based on Suspicion
- Hemoglobin electrophoresis or HPLC for hemoglobinopathies
- G6PD enzyme assay
- Osmotic fragility or EMA test for hereditary spherocytosis
- Bone marrow aspiration/biopsy if marrow failure suspected
- Viral serologies and autoimmune markers as needed
Consider Nutritional Deficiencies
- Serum iron studies, ferritin
- Serum B12 and folate levels
- Consider maternal B12 status in infants
Genetic Testing
- For IRIDA and congenital marrow failure syndromes when indicated
Treatment Considerations
- Address underlying cause (iron supplementation, B12/folate therapy)
- Transfusions in severe anemia with caution
- Monitor and manage complications (e.g., hypersplenism in thalassemia)

Speakers / Sources Featured

Primary Speaker: Dr. Anupam (expert in pediatric hematology)
Moderator / Commentator: Dr. Vaishnavi (and other participating pediatricians and hematologists during Q&A)
Various participants and questioners from the IAP Delhi Hematology session

Overall, the session provided a comprehensive clinical approach to diagnosing and managing anemia in children, emphasizing careful history, examination, and stepwise laboratory evaluation to differentiate between nutritional, hemolytic, marrow failure, and inherited causes of anemia.