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•Physiology•Definition•Classification• Clinical features•Specific disease and management
Iron deficiency anemiaAplastic anemiaThalassemiaG6PDAutoimmune
anemia
Developmental hematologyErythropoiesisHemoglobinThe red cells
Nelson Essential of Pediatric 5th edition
Hematopoiesis begins by 3 weeks of gestation with erythropoiesis in the yolk sac
By 2 month gestation the primary site has migrated to the liver
By 5 to 6 month’s gestation the process shift to the bone marrow.
During infancy virtually all marrows cavities are actively hematopoietic.
As the child grows hematopoiesis move to the central bone of the body (vertebrae ,sternum ,ribs and pelvis) and the marrows of extremities and the skull is replaced with fat.
Controlled by erytropoietin ; ▪ 90% made by by juxtaglomerular appratus .▪ 10% in the liver and elsewhere
Erytropoietin is a glycoprotein that stimulates the primitive pluripotential stem cell.
Then this cell differentiate along the erythroid line . The earliest recognizable erythroid cell invivo is
erythroblast. The immature RBC nucleus becomes pyknotic Then eventually this cells is released as
reticulocyte. The reticulocyte maintained mitocondria and pr-
synthetic capacity.
Glucose is the primary metabolic substrate for the red cell.Because the mature RBC does not contain mitoc. It metabolize gulcose only by anaerobic mechanismsThere are 2 major pathways
• Embden –Meyerhof (EMP)• Hexose monophosphate
shunt(HMS)2 ATP are generated ,ATP is used for cellular function ,membrane permeability In ability to maintain ATP ;shortened life span of RBCIn HMS ; it’s produced substrates that required to protect against rbc oxidation.
Anemia is defined as an hemoglobin level below the normal range .
The normal range varies with age ▪ Neonate : Hb <14 g/dl▪ 1- 12 months : Hb < 10 g/dl▪ 1-12 years : Hb < 11 g/dl
Illustrated Textbook of Paediactric Third edition by Tom Lissauer and Graham Clayden
Anemia may be defined either quantitatively or functionally (physiologically)
The diagnosis of anemia is determined by comparison of the patient with specific age and sex-specific normal values
Nelson Essential of Pediatric 5th edition
Peadiactric protocols for Malaysia Hospitals
The most useful classification is based on red cell indices and divides the anemia into microcytic , normocytic and macrocytic
Essential haematology A.V. Hoffbrand , J.E Pettit and P.A.H Moss
Microcytic hypochromic
Normocytic normocromic
Macrocytic
MCV < 75 flMCH < 27 pg
•Iron deficiency•Thalessemia•Anemia of chronic disease•Lead poisoning •Sideroblastic anemia
MCV 72-79 flMCH >26 pg
•Many haemolytic anemia •Anemia of chronic disease •Renal disease•Mixed deficiency •Bone marrow failure
MCV >85 fl
•Megaloblastic anemia :vit. B12 or folate dificiency
•Non megaloblastic :alcohol ,liver disease, aplastic anemia
Essential haematoly A.V. Hoffbrand , J.E Pettit and P.A.H Moss
Anisocytosis :Variations in size
Poikilocytosis :Variations in shape
Hypochromia :Increased central pallor*
Target cells : bull’s eye; central concentration of hemoglobin surrounded by
colorless area with peripheral ring of hemoglobin .
*the central pallor zone must be greater than 1/3 of the diameter of the RBC
THIN THICK
A, Hypochromic microcytic anemia. B, Megaloblastic anemia. C, Burr cells. D, Spur cells. E, Target cells. F, Microangiopathic hemolytic anemia (Schizocytes). G, Spherocytes. H, Heinz body hemolytic anemia.
•Introduction•Etiology•Classification of iron deficiency •Physiology•Clinical Presentation•Management
Iron deficiency anemia (IDA) is reported to be the most common nutritional deficiency in the world.
It affects 20% to 50% of the world's population and it is common in young children.
Many study shows it is due to ;low dietary intake , parasitic infections and demographic factors
In Malaysia, studies on children in under-privileged communities showed a high prevalence of A.lumbricoides, T. trichiura, hookworm, E. histolytica and G. duodenalis infections.
In Malaysia, a study in Hospital Kuala Lumpur in 1973 reported that severe trichuriasis in children produces chronic dysentery and, together with malnutrition and multiple parasitic infections, contributes to severe anemia and growth retardation
Intestinal Parasitic Infections and Micronutrient Deficiency : A Review M S Hesham, BSc, A B Edariah, MPHTM, M Norhayati, PhD, Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur
About 600 million individuals worldwide have IDA which in most cases, is of dietary origin, such as inadequate weaning.
IDA can no longer be considered a simple anemia that can be readily reversed by iron therapy.
Iron deficiency (ID) may be associated with abnormalities in cell-mediated immunity and the ability of neutrophils to kill several types of bacteria, and poorer psychomotor development and behavioral changes of young children.
Conclusion of this study ; The prevalence of ID and IDA among Kelantanese children is high, and is mainly attributed to prolonged breast feeding beyond six months of age and failure to introduce formula milk at later infancy
Prevalence and risk factors for iron deficiency in Kelantanesepre-school childrenSiti-Noor A S, Wan-Maziah W M, Narazah M Y, Quah B S
Inadequate supply of iron
Impaired absorption
Excessive demand of iron required for growth
Blood loss
a) Inadequate store at birth
b) Inadequate intake secondary to :socioeconomic facor, excessive cow ‘s milk diet , anorexia , etc
a) Chronic diarrhea
b) Malabsorption
c) Gastroinestinal abnormalities
a) Prematurityb) Adolescenc
ec) Menstruatio
n
a) Perinatal hemorrhage
b) Acute or chronic hemorrhage
c) Parasitic infestation
d) Idiopathice) Drug induced f) Hemoglobinuri
a
Paediatriic Problems In Tropical Countries 2nd Edition
Content• Body iron distribution and transport• Dietary iron • Iron absorption• Iron requirement
Essential haematology A.V. Hoffbrand , J.E Pettit and P.A.H Moss
The transport and storage of iron is mediated by 3 protiens
▪ Transferrin▪ The transferrin receptor▪ Ferritin
Transferrin delivers iron to tissues who have TR ,especially erythroblast.
Destruction or RBC release iron in the plasma ,and it is reutilized .
Only small proportion of plasma transferrin iron comes from dietary iron , absorbed through the duodenum and proximal jejunum.
Some iron is stored in reticuloendothelial cells as ferritin and hemosiderin
Iron in ferritin and hemosiderin is in ferric form It is mobilized after reduction to the ferrous
form , Vit. C is also involved.
Essential haematology A.V. Hoffbrand , J.E Pettit and P.A.H Moss
Factors favoring iron absorption
Factors reducing iron absorption
1. Haem Iron 2. Ferrous form 3. Acids (HCL ,Vit. C)4. Solubilizing agent (e.g
sugars ,amino.acid )5. Iron deficiency6. Increased erythropoiesis7. Pregnancy8. Hereditary haemochromatosis
1. Inorganic iron2. Ferric form3. Alkalis (antacids, pancreatic
secretion)4. Precipitating
agent ;phytates ,phosphates.5. Iron excess6. Decrease erythropiesis7. Infection8. Tea
Essential haematology A.V. Hoffbrand , J.E Pettit and P.A.H Moss
Stage Iron stores
Serum iron( μg/dl )
Trasnferrin saturation %
Serum ferritin( μg/l )
Anaemia
Normal Present 90-150 30 35 -
Iron depletion
Low < 60 20 10-30 -
Iron deficiency
- <60 <15 <10 -
Iron deficiency anemia
- <30 <10 <10 Microcytic hypochromic
Paediatric Problems In Tropical Countries 2nd Edition
A 1 year old infant requires : 8mg/day
Iron may come from Breast milk Infant formula Solid introduced at weaning e.g. cereals
Food Iron ,mg
Unit
MilkEggsCereal ,fortifiedVegetables Yellow GreenMeat Beef ,lamb ,liver Liver , baconFruits
0.5-1.51.23.0-5.0
0.1-0.30.3-0.4
0.4-2.06.60.2-0.4
LiterEachOunce
OunceOunce
OunceOunceOunce
Manual of Peadiactric Hematology and Oncology 4th edition by Philip Lanzkowsky
Growth is rapid during infancy and during puberty
Blood volume and body iron are directly related to
body weight throughout life .
Each kilogram gain weight requires 35-45mg body
iron.
The amount of iron in newborn is 75 mg/kg
If no iron is present in the diet or if bloods loss occur
the irons stores will depleted by 6 month (FT ) and by
4-6 month in preterm
The early stages of IDA often pass undetected in infancy . Infant can tolerate Hb 4-5 g/dl without any change in behavior.
In the toddler and school age ▪ Irritability ▪ Disinterest in play▪ Prolonged fatigue after physical activity▪ Anorexia
Mild degrees of anemia ▪ Alertness▪ Concentration▪ Learning capacity
A history of pica ,chronic diarrhea , dysentery , passage of bulky stool
Paediatric Problems In Tropical Countries 2nd Edition
Obese or underweightPallorKoilonychiaAngular stomatitisDigital clubbingSpleenomegaly ; 10-30% of cases In severe anemia
Tachycardia ,cardiac enlargement and cardiac failure
Paediatric Problems In Tropical Countries 2nd Edition
The diagnostic clue Microcytic , hypochromic anemia ( low
MCV and MCH ) Low serum ferittin
Peadiactric protocols for Malaysia Hospitals
INVESTIGATION RESULT
Hemoglobin Hb is low at acceptable level for age
Red cells indices Lower than normal (MCV,MCH,MCHC )
Blood smear Hypocromic and microcytic with anistocytosis and poikolocytosis generally occuring when the Hb levels below 10 g/dl
Reticulocyte count Usually normal
Serum ferritin (SF) The level of SF reflect the level of body iron stores. This test is sensitive and specific. A concentration of less than 12ng/ml is considered diagnostic of iron deficiency.
Serum iron , iron binding capacity and iron saturation %
Decreased serum iron , increased iron binding capacity and decreased iron saturation. This contrast with the anemia of chronic disorder when the serum iron and TIBC are both reduced
Therapeutic trial The most reliable criterion of iron deficiency anemia is the Hb response to an adequate therapeutic trial.A reticulocytosis with peak occurring between the 5th and 10th days followed by significant raised in Hb level
Manual of Pediactric Hematology and Oncology 4th edition by Philip Lanzkowsky
Iron deficiency anemia. a and b Erythrocytemorphology in iron deficiency anemia: ring-shaped erythrocytes (1), microcytes (2) faintly visible target cells (3), and a lymphocyte (4) for size comparison. Normal-sized erythrocytes (5) after transfusion.
Hemoglobinopathies Disoder of Heme synthesis caused by a
chemical Lead Pyrazinamide Isoniazid
Sideroblastic anemia Chronic infection or other inflammatory
statesManual of Pediactric Hematology and Oncology 4th edition by Philip Lanzkowsky
Refferences ;1.Peadiactric protols for Malaysia Hospitals2.Manual of Pediactric Hematology and Oncology 4th edition by Philip Lanzkowsky
TestsIron Deficiency Anemia Thalassemia Minor†
Anemia of Chronic Disease‡
Serum iron Low Normal LowSerum iron-binding capacity
High Normal Low or normal
Serum ferritin Low Normal or high Normal or high
Marrow iron stores Low or absent Normal or high Normal or high
Marrow sideroblasts* Decreased or absent Normal or increased Normal or increased
Free erythrocyte protoporphyrin #
High Normal or slightly increased
High
Hemoglobin A2 or F Normal High β-thalassemia; normal α-thalassemia
Normal
Red blood cell distribution width§
High Normal Normal/↑
Nelson Essential of Pediatric 5th edition
*an erythroblast having granules of ferritin
#protoporphyrin free in the blood rather than incorporated into erythrocytes; most is actually bound to zinc as zinc protoporphyrin
Indication : Very severe anemia and is complicated by CCF or superimposed infection
Method : Slow administration of <5 mls/kg weight of packed cells. Duration 4-6 hours
Drugs : i.v frusemide (1mg/kg) in severe anemia (Hb<4g/dl)
Content1.Introduction of Bone marrow failure and the causes.2.Definition3.Causes of aplastic anemia4.Clinical presenation5.Investigation6.Treatment
BMF may manifest as an isolated quantitative failure of one
cell line ,a single cytopenia or as pancyopenia, an acquired or inherited
failure of three cell line with a hypoplastic or aplastic marrow
Causes of Single Cell Line Failure and Generalized BMF
Failure of single cell line ( single cytopenia) Red Cells Inherited Diamond- Blackfan anemia (pure red cell aplasia) Congenital dyserythopoietic anemia Pearson syndrome Acqiured Idiopathic Transient erythroblastenia of childhood Secondary Drugs, infection ,malnutrition ,thymoma Hematologic condition Chronic Hemolytic anemia (with associated parvovirus infection) Chronic parvovirus infection
Failure of all three cell lines ( generalized pancytopenia ) Inherited Fanconi anemia Familial aplastic anemia Dyskeratosis congenita Acquired Idiopatic Secondary
Is a physiological and anatomical failure of the bone marrow characterized by a marked decrease or absence of blood-forming elements in the marrow and peripheral pancytopenia (decreased RBCs ,WBCs and platelets ).
Splenomegaly ,hepatomegaly and lymhadenopathy are not characterisic of this condition
Causes Of Aplastic Anemia
Inherited AcquiredFanconi anemiaFamilial aplastic anemia Dyskeratosis congenitaShwachman Diamond SyndromeDubowitz syndrome
Idiopathic (70 % or more cases)Secondary
• Drugs•6 –mecaptopurine•Methotrexate•Cyclophosphamide•Chloremphenicol
Chemicals :insecticides Toxin(e.g.,benzen ,carbon tetrachloride)IrradiationInfection
•Viral hepatitis•HIV•Infectious mononucleosis•CMV
Myelodysplastic syndrome
Clinical features of Aplastic Anemia
1. Anemia result in pallor ,easy fatigability ,weakness and loss of appetite
2. Thrombocytopenia leads to petechiae ,easy bruising ,severe nosebleeds and bleeding into the GIT and renal tract
3. Leukopenia leads to increased susceptibility to infections and oral ulcer that response poorly to antibiotic therapy.
4. Hepatosplenomegaly and lympadenopathy do not occur ; their presence suggest underlying leukemia
5. Hyperplastic gingivitis is also a symptom of aplastic anemia6. Special features ;
I. Skin ; Hyperpigmentation, café –au-lait spots,erythematous rash
II. Head ;Microcephaly ,micro-ophthalmiaIII. Mouth ; cleft lip,leukoplakiaIV. General : small stature
INVESTIGATION ; In Patient with Pancytopenia
1. Detailed drug history ,toxin and radiation exposure ,family history of aplastic anemia , physical examination for congenital anomalies
2. Blood count : reticulocyte count ,granulocyte count ,Hb ,Hct ,MCV , Platelet.
3. ANA and DNA titre ,Coomb’s test ,rheumatoid factor ,liver fx test
4. Viral serology :HIV,EBV ,Parvovirus ,hepatitis 5. Bone marrow aspiration
1. Bone marrow aspiration, also called bone marrow sampling, is the removal by suction of fluid from the soft, spongy material that lines the inside of most bones.
2. Bone marrow biopsy, or needle biopsy, is the removal of a small piece of bone marrow.
Essential haematology A.V. Hoffbrand , J.E Pettit and P.A.H Moss
Hb, WBC , Platelet LowHb, WBC , Platelet Low
Pancytopenia
BM aspiration
BM aspiration Acellul
ar
AbnormalLeukemia
MDSStorage disease
NormalLymphoma
Hypersplenism
-CTD
BM aspiration &biopsy
BM aspiration &biopsy
Abnormal- Leukemia
Hypocellular-Early
hypolastic anemia
Aplastic anemiaAplastic anemia
Disorder Age of Onset Characteristics TreatmentCongenitalDiamond-Blackfan syndrome (congenital hypoplastic anemia)
Newborn-1 mo; 90% are <1 yr of age
Pure red blood cell aplasia, autosomal recessive trait, elevated fetal hemoglobin, fetal i antigen present, macrocytic, short stature, web neck, cleft lip, triphalangeal thumb; late onset leukemia
Prednisone, transfusion
AcquiredTransient erythroblastopenia
6 mo-5 yr of age; 85% are >1 yr of age
Pure red cell defect; no anomalies, fetal hemoglobin, or i antigen; spontaneous recovery, normal MCV
Expectant transfusion for symptomatic anemia
Idiopathic aplastic anemia (s/p hepatitis, drugs, unknown)
All ages All cell lines involved; exposure to chloramphenicol, phenylbutazone, radiation
Bone marrow transplant, antithymocyte globulin, cyclosporine, androgensNelson Essential of Pediatric 5th edition
FamilialFanconi syndrome Before 10 yr of age; mean is
8 yrAll cell lines; microcephaly, absent thumbs, café au lait spots, cutaneous hyperpigmentation, short stature; chromosomal breaks, high MCV and hemoglobin F; horseshoe or absent kidney; leukemic transformation; autosomal recessive trait
Androgens, corticosteroids, bone marrow transplant
Paroxysmal nocturnal hemoglobinuria
After 5 yr Initial hemolysis followed by aplastic anemia; increased complement-mediated hemolysis; thrombosis; iron deficiency
Iron, bone marrow transplant, androgens, steroids
Dyskeratosis congenita Mean 10 yr for skin; mean 17 yr for anemia
Pancytopenia; hyperpigmentation, dystrophic nails, leukoplakia; X-linked recessive; lacrimal duct stenosis; high MCV and fetal hemoglobin
Androgens, splenectomy, bone marrow transplant
Familial hemophagocytic lymphohistiocytosis
Before 2 yr Pancytopenia; fever, hepatosplenomegaly, hypertriglyceridemia, CSF pleocytosis
Transfusion; often lethal; VP-16, bone marrow transplantation, IVIG, cyclosporine
InfectiousParvovirus Any age Any chronic hemolytic
anemia, typically sickle cell; new-onset reticulocytopenia
Transfusion
Epstein-Barr virus (EBV) Any age; usually <5 yr of age
X-linked immunodeficiency syndrome, pancytopenia
Transfusion, bone marrow transplantation
Viral-associated hemophagocytic syndrome (CMV, HHV-6, EBV)
Any age Pancytopenia; hemophagocytosis present in marrow, fever, hepatosplenomegaly
Transfusion, antiviral therapy, IVIG
Abu Hurairah r.a meriwayatkan bahawa Rasulullah SAW bersabda : "Umatku talah dikurniakan dengan lima perkara yang istimewa yang belum pernah pun diberikan kepada sesiapa pun sebelum mereka. Bau mulut daripada seorang Islam yang sedang berpuasa adalah lebih harum di sisi Allah daripada bau haruman kasturi. Ikan-ikan di lautan memohon istighfar(keampunan) ke atas mereka sehinggalah mereka berbuka puasa. Allah mempersiapkan dan menghiasi jannah yang khas setiap hari dan kemudian berfirman kepadanya : " Masanya telah hampir tiba bilamana hamba-hambaKu yang taat akan meninggalkan segala halangan-halangan yang besar (di dunia) dan akan mendatangimu. Pada bulan ini syaitan-syaitan yang durjana dirantaikan supaya tidak menggoda mereka ke arah maksiat-maksiat yang biasa mereka lakukan pada bulan-bulan selain Ramadhan. Pada malam terakhir bulan Ramadhan (orang-orang Islam yang berpuasa ini ) akan diampunkan.Maka sahabat-sahabat Rasulullah SAW pun bertanya : "Wahai Pesuruh Allah adakah itu malam Lailatul Qadr?" Dijawab oleh Rasulullah SAW "Tidak tetapi selayaknyalah seorang yang beramal itu diberi balasan setelah menyempurnakan tugasnya"