بســم اللــه الـرحمـن الـرحيــم

1. بســم اللــه الـرحمـن الـرحيــم Blood diseases. Dr. Abed M. Al Hazmi. Associated prof. of pediatrics. King A/Azziz University Jeddah KSA.

2. Definition of ANEMIA: Anemia is defined as reduction in red blood cell mass, below 2SD of the range of values for that age, and sex found in healthy person, i.e. (<-2SD).

3. Normal Values ( mean and lower limit of normal (-2 SD)),for Hemoglobin, and Mean Corpuscular Volume (MCV) at various Ages. • Hemoglobin (g/dl) MCV (fl) Hematocrit (%). • Age Mean -2SD Mean -2SD Mean -2SD • ____________________________________________________________________ • Cord blood 16.5 13.5 108 98 51 42. • 1 WK 17.5 13.5 107 88 54 42. • 2 WK 16.5 12.5 107 86 51 39. • 1 mo 14.0 10.0 104 85 43 31. • 2 mo 11.5 9.0 96 77 35 28. • 3-6mo 11.5 9.5 91 74 35 29. • 0.5-2yr 12.0 10.5 78 70 36 33. • 2-6yr 12.5 11.5 81 75 37 34. • 6-12YR 13.5 11.5 86 77 40 35. • 12-18YR • Female 14.0 12.0 90 78 41 36. • Male 14.5 13.0 88 78 43 37. • 18-49yr • female 14.0 12.0 90 80 41 36. • Male 15.5 13.5 90 80 47 41.

4. Classification of anemia: • A useful classification of the anemia is to divided anemia into three large groups by the RBC CELL Mean Corpuscular Volume (MCV).

5. Microcytic Macrocytic Normocytic MCV < 76 MCV > 96 MCV 76-96 femto. Iron deficiency Folate deficiency Hemolytic anemia's Thalassemia Vit. B12 Deficiency Anemia of chronic dis. Lead poisoning cong. Hypoplastic Acute blood loss Sideroblastic anemia anemia.(D.B.S) Aplastic anemia. Anemia of chronic Preleukemia. SCA. G6PD. Disease Liver disease Fanconi anemia. Copper deficiency Hypothyroidism Infiltrative process. Thiamine deficiency.

6. Others Classifications of Anemia: • anemia may be classified into the following 3 primary categories: • 1- Decreased red cell production • 2- Increased red cell destruction (hemolysis) • 3- Anemia due to blood loss.

7. Clinical features of anemia: • NB: When oxygen delivery by RBC to tissues is decrease: the body responds by compensatory mechanism include: • 1- Increase cardiac output 2- Increase 2-3 DPG.(diphosphoglycerate) • 3- Increase EPO production 4- Shift of blood to vital organs. • The clinical effects of anemia are influenced by 4 major factors: • 1- The speed of onset 2- Severity of anemia. • 3- Age of onset 4- The HGB – O2 dissociation curve.

8. Symptoms: • 1- Shortness of breath (particularly on exercise). • 2- Weakness. • 3- Lethargy. • 4- Anorexia. • 5- Headache. • 6- Heart failure. • 7- Palpitation ( older children & Adult ).

9. Signs: • General signs: • 1- Pallor (mucous membrane). Present when Hgb <10g/dl. • 2- Hyper dynamic circulation ( tachycardia, bounding pulses). • 3- Features of heart failure. • 4- Failure to thrive. • Specific signs: • 1- Jaundice ( Hemolytic anemia ). • 2- Leg ulcer ( SCA ). • 3- Koilonychias ( spoon nail ). • 4- Bone deformities ( Thalassemia). • 5- Smooth red painful tongue ( vit. B12 Def. ).

10. Anemia in the Neonate & First three months of age: • Some types of anemia occur at birth or in early infancy. They are due to • Physiological, • Acquired, • Inherited,

11. A two months old infant seen in ER, because of one day history of S.O.B. and cough. • He is a product of S.V.D, full term pregnancy. • A CBC was done showed: • WBC 15000/mm3. • RBC 4.5 x 10 12/mm3. • Hgb 8.2 g/dl. • MCV 80 pf. • Platelet 250000/mm3. • What is your comment on this CBC ? • What is your management ?

12. Physiological anemia & Anemia of prematurity • Physiological anemia: developed in full term baby by age of 6 – 12 wks with Hb ( 8.0 – 11 g/dl ). • Anemia of prematurity: developed preterm baby by age of 4 -6 wks with Hb level ( 4 – 10 g/dl ). • Mechanisms of these anemia: • 1- Cessation of erythropoietin (EPO) production. • 2- Shortened survival of fetal RBC. • 3- Expansion of blood volume due to rapid wt. gain. • 4- After birth the ratio of HbF/HbA decreased & (2-3 DPG) increased, this result in increased O2 delivery to tissue and decreased hypoxia which stimulate EPO production.

13. A two months old infant seen in ER, because of one day history of S.O.B. and cough. • He is a product of S.V.D, full term pregnancy. • A CBC was done showed: • WBC 15000/mm3. • RBC 4.5 x 10 12/mm3. • Hgb 8.2 g/dl. • MCV 80 fl. • Platelet 250000/mm3. • What is your comment on this CBC ? • What is your management ?

14. Clinical manifestations: • Pure physiological anemia of infancy almost always fully compensated with no symptoms or signs, unless there is/are other process associated e.g. neonatal infection, blood loss, hemolysis. • Therapy: • Usually required no therapy other than ensuring that diet contains the essential nutrients for normal hematopoiesis as folic ac., & iron. • Transfusion when the baby is not growing properly, apneic spell, bradycardia, infections. • Recombinant human EPO, plus iron & folic ac. When blood transfusion is not possible.

15. Acquired anemia in the neonate: • Blood loss: • A- Obstetric as a cause of blood loss: • 1- placenta previa. • 2- Abrupt placenta. • 3- Hematoma of the umbilica cord. • 4- Rupture of the umbilical cord.

16. B- Occult blood loss: • 1- Fetomaternal bleeding: • A- Placenta malformation. • B- Obstetric procedure ( Traumatic amniocentesis, external or internal cephalic version, breech delivery ). • C- Spontaneous. • C- Fetoplacenta bleeding: • 1- Chorioangioma, Choriocarcinoma. • 2- Cesarean section ( infant hold above placenta). • 3- Tight nucal cord or occult cord prolapse>

17. This is the picture of twin delivery:What is your description ?What are the complications in the first & second twin?

18. D- Twin – Twin Transfusion. • E- Hemolysis: • 1- Rh, ABO, & minor blood gr. Incompatibility. • 2- Infection, DIC, Vit. E deficiency.

19. Hereditary RC Disorders: • A- Metabolic defect as G6PD, Pyruvate kinase def. • B- RBC membrane defect as spherocytosis, elleptocytosis, somatocytosis. • Hemoglobinopathies: • A- Alfa and gamma thalassemia syndrome. • B- Alfa and gamma chain structural abnormal.

20. Diminished RBC production: • A- Diamond – Blackfan Syndrome. • B- Congenital leukemia. • C- Infection ( specially Rubella, Parvovirus). • D- Osteopetrosis.

21. Nutritional Anemia:( due to deficiency of substances essential for erythropoiesis) • A- Iron deficiency anemia: (very common). • (Uncommon problem in childhood). • B- Megaloblastic anemia: due to deficiency of Vit B12 or folic acid. • C- Anemia due to protein malnutrition: • D- Vit C deficiency anemia: (associated with scurvy or pyridoxine deficiency).

22. Test name Result Refer. Range Unit. • ___________________________________________________________ • WBC ( White blood Cell Count). 6.7 4.5 - 11.5 K/ul • RBC ( Red blood Cell Count ). 3.15 4.00 – 6.00 M/ul • . • Hemoglobin ( Hb ). 8.5 12 – 16. g/dl • Hematocrit ( HCT ). 30.00 36 – 54 % . • Mean Corpuscular Volume) MCV. 60.00 70 – 80 fl. • Mean Corpuscular Hb MCH 23.00 27 – 32 pg. • Mean Cor. Hb Conc. MCHC 28.00 32- 36 %. • RDW ( RBC distribution width ) 17.1 11.5 – 14.5 %. • ( MCV/RBC ). • Platelets ( PLT ) 240 150 – 450 K/ul. • 1- Comment on this CBC. • 2- What is your most likely diagnosis ?.

23. Iron Deficiency Anemia( Is the most common anemia in infancy & childhood ) • Etiology: • 1- Inadequate intake of Iron: • A- Prolonged breast feeding. Rare before age of 6 mon. • B. Preterm baby ( low birth weight ) & Unusual perinatal blood loss • C- Poverty. 2- Blood loss: A- Occult bleeding from GIT as Peptic ulcer, Meckel diverticulum's, Polyps, heamangioma, Inflammatory bowel disease, hookworm infest. B- In some areas occult blood loss from GIT due to consumption of whole cow's milk ( exposure to a heat-labile protein ). 3- Defective absorption of Iron: A- Malapsorption syndrome. B- Excess phosphate & phytate in diet e.g. cereals. C- Achlorhydria ( ). 4- Increase demand for iron: A- Rapid growing premature and growing children. B- Menstruating females. C- Convalescence from disease.

24. Clinical picture: • 1- Pallor is the most important sign of anemia. • 2- Compensatory mechanisms ( in mild & moderate IDA Hb 6-10 g/dl). • A- Increased level of 2,3 DPG ( diphospho – glycerate ). • B- Shift of the oxygen dissociation curve. 3- Irritability, pica( pagophagia), and anorexia in severe anemia Hb <5 g/dl. 4- Iron deficiency with or without anemia have effects on neurologicl and intellectual function as attention span, alertness, and learning in both children & adolescent. 5- Enlargement of the spleen in 10%. 6- Angular stomatitis, red glazed tongue. 7- Nails are brittle, striated and loss their luster, in severe anemia there is spooning of nails. 8- Hemic mur. In severe anemia.

25. Investigations: ( follow a sequence) • Hb & RBC are reduced. And disappearing of B.M. hemosiderin. • S. Ferritin decreased. • Iron-binding capacity of the serum (s. transferrin) Increased. • WBC are normal • Platelet Increased (in severe IDA Decreased). • B.M. Hypercrllular with erythrioid hyperplasia. • AS the deficiency of iron progress the RBC • 1- Become small (Microcytic), Decrease their Hgb content (Hypochromic). • 2- RBCs become deformed (Poikilocytosis). • 3- Increase red cell distribution width (RDW).

26. Differential diagnosis: • IDA Should be differentiated from: • 1- Thalassemia Trait. • 2- Lead poisoning. • 3- Sideroblastic anemia. • 4- Chronic diseases. • 5- Copper deficiency. • 6- Hemoglobin E. • 7- Pyridoxine deficiency.

27. Differential diagnosis: • 1- Alfa & Beta Thalassemia trait. Hb electrophoresis ( Level of Hb A2 & Hb F are increased ). 2- Lead poisoning ( level of lead increased ). 3- Thalassemia major Hemolytic manifestations. 4- Pyridoxin deficiency ( V.B6 level decrease ). 5- Chronic disease ( S.iron & Iron-binding capacity are reduced but S. ferritin increased.

28. Treatment: • Oral administration of Ferrous salts ( Sulfate, Gluconate, Fumarate ) • 4-6 mg/kg of elemental iron in three divided doses. • Iron dextran IM • Vit C Increases absorption of Iron from food. • Stop bleeding and treat parasitic infestation. • Blood transfusion is indicated when: 1- Severe anemia ( Hb < 4g/dl). 2- Anemia associated with infection that may interfere with iron absorption. • Family education and diet to prevent IDA in infancy.

29. Response to iron therapy: • 12 – 24 hr. : replacement of intracellular iron enzymes ( dec. irritability, increase appetite ). • 36 – 48 hr. : Initial bone marrow response ( erythroid hyperplasia ). • 48 – 72. hr. : Reticulocytosis. • 4 - 30 days : Increase in Hb ( 0.5g/dl/24 hr. • 1 – 3 months : Repletion of iron stores.

30. Megaloblastic Anemia • Vitamin B-12 Deficiency: • Requirements: 1-2 mic.g/d. • Sources: Animal products ( liver, Kidney). • Absorption: Combined with IF absorbed in the terminal ileum. • Functions: Essential for hemopoiesis & NS integrity. • Storage: 2 mg. are stored in the liver (sufficient for 2-4 yr.).

31. Causes of Vit.B-12 Deficiency: • A- Poor dietary intake. Rare in children ( poverty & Vegan). • B- Gastric causes. Rare in children. 1- Pernicious anemia ( meanly in adult). 2-Congenital lack or abnormal intrinsic factor (IF). 3- Total or partial gastrectomy.

32. C- Intestinal causes. Is the usually causes in children. 1- Intestinal stagnant synd. Jejunal devirticulosis, blind- loop stricture, ect (B12 utilization by bacteria). 2- Chronic tropical sprue. 3- Ileal resection & Cohn's disease. D- Congenital deficiency of Vt.B12 carrier proteins. Transcobalamin Def. ( Tarnscobalamin II ). E- Others: (rare without clinical importance). Celiac dis. Sever pancreatitis, HIV infection.

33. Clinical manifestations: The onset usually insidious. • 1- Mild jaundice (due to ineffective erythropoiesis). • 2- Glossitis ( a beefy-red, sore tongue). • 3- Angular stomatitis. • 4- Signs of malabsorption with wt. loss. • 5- Purpura due to thrombocytopenia. • 6-Widespread melanin pigmentation. • 7- Vit. B12 Neuropathy (subacute combined degeneration of the cord). • Affecting the sensory nerves and posterior & lateral columns. It is symmetrical affecting the lower limbs more than the upper. • Ataxia, Paresthesias, Hyporeflexia, Babinki & Clonus +.

34. Laboratory Findings: • 1- CBC: Macrocytic red cell indices, evaluates for cytopenias. • WBC and platelet may be moderately reduced. • Reticulocyte count: is low in relation to the degree of the anemia. • 2- Bone marrow: Should be consider for any child with more than one abnormal cell line on the CBC. • 3- Serum B12 level.

35. Treatment: • Initial dose: IM. • 10-50 mcg/d for 5-10 d, followed by 100-250 mcg/dose q2-4 wk. • OR. 1mg/dose IM . If there is evidence of neurological involvement 1mg/d IM for 2 wks. Maintenance : 1 mg IM monthly for life.

36. Folic Ac. Deficiency: • Requirement: 100 – 200 mic.g/d. • Sources: Greens vegetables, fruits, liver. • Absorptions: Small intestine. • Functions: DNA synthesis, and a.a. interconversions.

37. Causes of Folate Deficiency: • 1- Inadequate dietary intake: • 2- Inadequate absorption: • 3- Antifolate medications (e.g: Methiotraxate): • 4- Medications that impair absorption (eg. Ant convulsions). • 5- Increased use ( eg, Chronic hemolysis such as SCA).

38. Clinical manifestations: • Onset 4-7 months of age the infant usually of low birth wt. 0r significantly underweight ( marasmus, or kwashiorkor ). • They present with: • 1- Megaloblastic Anemia. • 2- Irritability. • 3- Failure to gain wt. • 4-Chronic diarrhea. • 5- Hemorrhage due to thrombocytopenia.

39. Laboratory Findings: • 1- CBC: Macrocytic red cell indices, evaluates for cytopenias. • WBC and platelet may be moderately reduced. • Reticulocyte count: is low in relation to the degree of the anemia. • 2- Bone marrow: Should be consider for any child with more than one abnormal cell line on the CBC. • Red blood cell folate level (The best test for metabolically active folate). • Serum Folate measures the circulating pool.

40. Treatment: • Folic ac. 1-5 mg/d for 3-4 wks. Orally.