Classification , Epidemiology, Etiology Clinical Features, Diagnosis, Complications , Management, Prognosis

1. Hemolytic Anemia in Children
Classification, Epidemiology, Etiology
Clinical Features, Diagnosis, Complications,
Management, Prognosis
Prof. Imran Iqbal
Fellowship in Pediatric Neurology (Australia)
Prof of Paediatrics (2003-2018)
Prof of Pediatrics Emeritus, CHICH
Prof of Pediatrics, CIMS
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 - Definition
• 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. Anemia – Physiology
• RBC count in blood is about 5 million/ul
• Average lifespan of RBCs is 120 days
• About 1 % of the body's total red blood cells are produced
and replaced per day
• Anemia occurs when there is:
-- decreased production of RBCs
-- increased destruction / loss of RBCs

6. Anemia in Children – Etiology
• Decreased production –
-- Nutritional substrate deficiency – Iron, Folic acid
-- Chronic diseases – CKD, JIA, Hypothyroid
• Chronic Blood Loss – Worms, Visible chronic bleeds
• Aplastic Anemia – Bone marrow Failure
• Bone Marrow Replacement – Leukemia, lymphoma
• Hemolytic Anemia – increased RBC breakdown
-- Genetic, congenital defects
-- Acquired disorders

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

8. Hemolytic Anemia – Physiology
• Bone Marrow produces RBCs
• Old and damaged RBCs are destroyed in the reticulo-
endothelial system especially spleen
• In Hemolytic Anemia, life span of RBCs is shortened
• RBCs destruction is increased
• Damaged RBCs are taken up by the Reticulo-endothelial
system in liver and spleen

9. Hemolytic Anemia – Pathophysiology
• Hemoglobin and RBC count in blood is reduced
• Spleen and Liver are enlarged
• Cellular hypoxia stimulates erythropoietin production
• Hemolytic Anemia results in Erythroid Hyperplasia with an
increase in RBC production many times

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

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

12. Hemolytic Anemia in Children
Etiology and Classification

13. Hemolytic Anemia – Pathological Classification
• Intravascular Hemolysis : (rare) – Hemoglobinuria is seen
-- G 6-PD deficiency (Glucose 6-Phosphate Dehydrogenase
Deficiency)
-- Hemolytic reactions after Blood Transfusion
-- Malaria (Blackwater Fever)
• Extra-cellular Hemolysis : (common)
-- RBC destruction occurs in Reticulo-endothelial cells in liver
and spleen
-- seen in most of the hemolytic anemias

14. Hemolytic Anemia – Pathology
Extravascular vs Intravascular Hemolysis

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

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

17. Hemolytic Anemia – 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

19. Hemolytic Anemia in Children
Clinical Features

20. Case Scenario
• A 2 year 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.

21. Hemolytic Anemia - Clinical Features
• Anemia (mild to severe, may be masked by blood transfusion)
• Jaundice (unconjugated) may be seen
• Splenomegaly (to a variable degree) in most children
• Bony deformities (in severe chronic cases especially
Thalassemia)
• Gall stones (bilirubin stones usually in Hereditary
Spherocytosis)

22. Hemolytic Anemia in Children
Diagnosis

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

24. Hemolytic Anemia - Lab Diagnosis
• Hemoglobin - low
• 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

25. Hemolytic Anemia - 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)

26. Hemolytic Anemia - Diagnostic algorithm

27. Hereditary Spherocytosis

28. Hereditary Spherocytosis – Clinical Picture
• Autosomal dominant – other family members affected
• Severity of disease is variable
• Mild to moderate hemolysis
• Newborns may have anemia and hyperbilirubinemia
• Children have mild anemia
• Gall stones (Calcium bilirubinate) can develop
• Spleen is enlarged

29. Hereditary Spherocytosis
• Diagnosis
• Hb normal to low
• Retic Count > 2 %
• MCV and MCH are low, MCHC increased
• Blood film shows spherocytes
• Management
• In severe disease, splenectomy is indicated

30. Sickle Cell Anemia

31. 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

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

33. Beta Thalassemia

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

35. Beta Thalassemia Major

36. Beta Thalassemia Major
• Diagnosis
• Peripheral blood film shows Microcytic Hypochromic Anemia
• Hb electrophoresis - Hb F
• Thalassemia Gene tests in peripheral blood
• Management
• Frequent Blood Transfusions and Iron chelation are needed
• Hydroxyurea may reduce need of blood transfusions
• Iron overload is managed by Iron Chelation therapy
• Bone Marrow Transplant can cure the patient

37. Differential Diagnosis of Microcytic Hypochromic Anemias
Iron deficiency Anemia and Thalassemia Major
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

38. Glucose 6-Phosphate Dehydrogenase Deficiency
(G6PD)

39. 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 (Primaquine, Sulphonamides) or
infections
• Severe intravascular hemolysis results in sudden severe
anemia and hemoglobinuria (cola-colored urine)

40. Glucose 6-Phosphate Dehydrogenase Deficiency
(G6PD)
• Diagnosis:
• Blood G6PD levels are low
• Management
• Blood Transfusion is needed urgently in cases of sudden
intravascular hemolysis
• Life long avoidance of specific drugs is important for
prevention of acute hemolysis

41. Autoimmune Hemolytic Anemia

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

43. 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 blood smear provides a guide for further specific
investigations
• Hemoglobin electrophoresis is important investigation for
Thalassemia
• Remember to send a blood sample for Hemoglobin
electrophoresis before blood transfusion