Management of Anemia Faiz7

•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


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


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.

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


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


Obese or underweightPallorKoilonychiaAngular stomatitisDigital clubbingSpleenomegaly ; 10-30% of cases In severe anemia

Tachycardia ,cardiac enlargement and cardiac failure


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/↑


*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.

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"

Management of Anemia Faiz7

Documents

Transcript of Management of Anemia Faiz7