Hemolytic anemia in children

1. Hemolytic Anemia
in Children
Prof. Imran Iqbal
Prof of Paediatrics (2003-2018)
Prof of Pediatrics Emeritus, CHICH
Multan, Pakistan

2. In the name of Our Creator
Allah,
the most Gracious,
the most Merciful

3. OBJECTIVES
• What is Hemolytic Anemia ?
• What are the different types ?
• How to make a diagnosis ?
• What investigations to be performed ?
• What is the management ?

4. Anemia
• Hemoglobin or RBC volume less than normal
(according to age and sex)
• Newborns: 17-22 gm/dl
• One (1) week of age: 15-20 gm/dl
• One (1) month of age: 11-15gm/dl
• Children: 11-13 gm/dl
• Adult males: 14-18 gm/dl
• Adult women: 12-16 gm/dl
• Men after middle age: 12.4-14.9 gm/dl
• Women after middle age: 11.7-13.8 gm/dl

5. Causes and Types of Anemia
• Nutritional deficiency Anemia
- Iron deficiency
- Folic acid / B12 deficiency (megaloblastic anemia)
• Hemolytic Anemia
- Thalassemia
• Hypoplastic anemia (Bone marrow suppression)
• Anemia of chronic disease
- Chronic Liver disease
- Chronic kidney disease
- Chronic inflammation
• Malignancies / Marrow replacement
- Leukemia, Lymphoma
- Other malignancies

6. HEMOLYTIC ANEMIA
• Definition:
Anemias which result from
an increase in RBC destruction in the body
with
increased erythropoiesis in Bone Marrow

7. Physiology
• Bone Marrow produces RBCs
• Life span of RBCs is 120 days
• RBC count in blood is about 5 million/ul
• Old and damaged RBCs are destroyed in the
reticulo-endothelial system especially spleen
• 1 % of circulating RBCs are destroyed daily and
replaced by new RBCs

8. Pathophysiology of Hemolytic Anemia
• In Hemolytic Anemia, life span of RBCs is
shortened
• RBCs destruction is increased
• Hemoglobin and RBC count in blood is
reduced
• Cellular hypoxia stimulates erythropoietin
production
• Bone marrow becomes hyperplastic and
increases its output of erythrocytes

9. Pathology
• Increased RBCs destroyed
- Anemia
- Blood Unconjugated bilirubin
- Hepatosplenomegaly (RE hyperplasia)

10. Pathology
• More RBCs produced
- Reticulocytes (immature RBCs) in blood
- Normoblasts seen in blood
- Skeletal deformities (Bone marrow expansion)

11. Etiology and Classification

12. Etiological classification of Hemolytic Anemia
• Cellular Defects : (hereditary diseases)
when RBCs are abnormal
• Extra-cellular Defects : (acquired diseases)
with defects in environment of RBCs

13. Cellular Defects
• RBC membrane defects:
- Hereditary spherocytosis
• RBC enzyme deficiency:
- G 6-PD Deficiency
• Hemoglobin abnormalities
- Thalassemia
- Sickle cell anemia

14. Extra-cellular Defects
• Immune Hemolysis (due to antibodies)
-- Hemolytic disease of newborn (Rh-
incompatibility)
-- Auto-immune Hemolytic Anemia
• Non Immune Hemolysis:
- Physical Damage to RBCs – DIC, Burns
- Infections – malaria, bacterial sepsis

16. Clinical Features

17. Case Scenario
A 18 months old child
presents to the OPD with the
complaints of poor feeding
and frequent crying for the
last 6 months.
On examination, weight of the
child is 8 kg. He has marked
pallor on his tongue and
hands. His abdomen is
distended. Liver and spleen
are palpable by 8 cm each
below the costal margin.

18. Approach to Hemolytic anemia
1. Clinical Diagnosis
2. Laboratory confirmation of Hemolysis
3. Determination of precise etiology

19. Clinical Features
• Anemia (mild to severe, may be masked by
blood transfusion)
• Jaundice (unconjugated, in some cases)
• Splenomegaly (in all cases)
• Bony deformities (in severe chronic cases
especially Thalassemia)
• Gall stones (bilirubin stones usually in
Hereditary Spherocytosis)

20. Lab Diagnosis
• Hb
• Reticulocyte Count > 2 %
• Normoblasts (peripheral blood film)
• Peripheral blood film (specific changes in
different diseases)
• Hemoglobinuria (dark brown color urine
containing Hemoglobin seen in intravascular
hemolysis)
• Bone Marrow exam (rarely needed) shows
Erythroid Hyperplasia

21. Lab Diagnosis for Etiology
• Peripheral blood film (spherocytes, normoblasts)
• Hb electrophoresis
- Hb F seen in Thalassemia major
- Hb S seen in Sickle Cell Anemia
• G 6-PD enzyme estimation in blood (for G 6-PD
deficiency)
• Direct Coombs test for antibodies to RBCs in
immune hemolysis
• Hemoglobinuria (dark brown urine in
intravascular hemolysis)

22. Diagnostic algorithm for Hemolytic Anemia

23. Hereditary Spherocytosis
• Autosomal dominant
• Mild to moderate hemolysis
• Newborns may have anemia and
hyperbilirubinemia
• Children have mild anemia
• Gall stones (Calcium bilirubinate) are common
• Spleen is enlarged

24. Hereditary Spherocytosis
• Hb normal to low
• Retic Count > 2 %
• MCHC increased
• Blood film shows spherocytes
• In severe disease, splenectomy is indicated

25. Blood film in Hereditary Spherocytosis

26. Beta Thalassemia Major
• Most common Hemolytic anemia in Pakistan
• Autosomal recessive
• Thalassemia gene carrier rate in Pakistan is 6 %
• Hemoglobin in blood is mainly Hb F
• Severe hemolysis
• Anemia starts in first six months of life
• Very large spleen
• Significant bony changes
• Peripheral blood film shows Target cells

27. Beta Thalassemia Major

28. Beta Thalassemia Major
• Diagnosed by :
- Hb electrophoresis
- Thalassemia Gene tests in peripheral blood
• Frequent Blood Transfusions and Iron chelation
are needed
• Hydroxyurea may reduce need of blood
transfusions
• Life span shortened due to multiple
complications
• Bone Marrow Transplant can cure the patient

29. Sickle Cell Anemia
• Seen in Baluchistan, Middle East
• Autosomal recessive
• Hemoglobin in blood is mainly Hb S
• RBCs become sickle-shaped with reduced Oxygen
• Sickled RBCs block capillaries resulting in tissue
hypoxia
• Severe vaso-occlusive pain in bones and limbs
starts at an early age
• Anemia mild to moderate
• Bacteremic infections are common

30. Sickle Cell Anemia
• Diagnosed by:
- sickling test
- Hb electrophoresis
• Blood Transfusions may be needed during acute
complications
• Management of Painful crisis needs hydration
analgesics and blood transfusion
• Hydoxyurea increases Hb F and reduces hypoxic,
painful episodes

31. Glucose 6-Phosphate Dehydrogenase Deficiency
(G6PD)
• X-linked recessive, seen in males
• G6PD enzyme is deficient in RBCs
• Glucose 6-Phosphate Dehydrogenase enzyme
protects against Oxidative reactions in RBCs
• G6PD Usually produces episodic severe hemolysis
after exposure to certain drugs or infections
• Severe intravascular hemolysis results in sudden
severe anemia and hemoglobinuria (cola-colored
urine)
• Blood Transfusion is needed urgently

32. Glucose 6-Phosphate Dehydrogenase Deficiency
(G6PD)
• Diagnosis: Blood G6PD levels are low
• Life long avoidance of specific drugs is
important for prevention

33. Autoimmune Hemolytic Anemia
• Seen in older children
• Anti RBC antibodies develop in the body
• Progressive anemia
• Spleen is enlarged
• Direct Coombs test is positive
• Blood Transfusions may be needed
• Management includes steroids and other
immunosuppresants
• Disease may last for months to years

34. Comparison of
Iron deficiency Anemia and Thalassemia
Iron deficiency Anemia
• Onset in late infancy
• Slow developing anemia
• No splenomegaly
• Serum Ferritin low
• Reticulocyte count < 2 %
• Hb electrophoresis shows
Hb A
Thalassemia
• Onset in early infancy
• Rapidly developing anemia
• Splenomegaly
• Serum Ferritin raised
• Reticulocyte count > 2 %
• Hb electrophoresis shows
raised Hb F

35. Take Home Message
• Hemolytic Anemias are common in children
• Anemia and Splenomegaly are important signs
on physical examination
• Low Hb and raised Retics Count in blood are
indicators
• Peripheral smear provides a guide for further
specific investigations
• Remember to send a blood sample for Hb
electrophoresis before blood transfusion