Approach to childhood anemia
This presentation is the property of its rightful owner.
Sponsored Links
1 / 105

Approach to Childhood Anemia PowerPoint PPT Presentation


  • 113 Views
  • Uploaded on
  • Presentation posted in: General

Approach to Childhood Anemia. H. Tamary Hematology, Schneider Children’s Medical Center of Israel. Normal Hemoglobin and MCV Values in Term Infant. Hb MCV (g/dL)(fl) Day 119.0±2.2119 ±9.4 12 weeks11.3 ±0.988 ±7.9. Regulation of Erythropoiesis.

Download Presentation

Approach to Childhood Anemia

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Approach to Childhood Anemia

H. Tamary

Hematology, Schneider Children’s Medical Center of Israel


Normal Hemoglobin and MCV Values in Term Infant

HbMCV

(g/dL)(fl)

Day 119.0±2.2119 ±9.4

12 weeks11.3 ±0.988 ±7.9


Regulation of Erythropoiesis


Hemoglobin Concentration- Different Gestational Age


Globin Synthesis in Embryo, Fetus and Adult


Decline in Fetal Hemoglobin


Criteria for Identifying Children with Low Hemoglobin Values

AgeHemoglobin

(g/dL)

6ms –11 years<11

>11 male<13

>11 female <12


Etilogical Classification of Anemia (I)

A. Blood loss

B. Excessive blood destruction

1. Intrinsic factors

a. Defects of membrane: spherocytosis, elliptocytosis

b. Defects of hemoglobin

  • Structural anomaly: HbS

  • Synthesis anomaly: thalassemia


Etilogical Classification of Anemia (II)

c. Enzymatic defect: G6PD deficiency, pyruvate kinase

2. Extrinsic factors

a. Immune mechanisms: Rh, ABO incompatibility, autoimmune hemolytic anemia

b. non-immune mechanisms: infections


Etilogical Classification of Anemia (III)

C. Decreased production

1. Deficiency of substance: iron, Vit B12, folic acid

2. Mechanical interference: malignant replacement

3. BM failure

a. Primary: aplastic anemia

b. Secondary: renal, liver disease


Etiological Classification of Neonatal Anemia

  • A.Blood loss-fetal to fetal, feto-maternal, traumatic delivery

  • B.Increased blood destruction-Rh, ABO or minor blood group incompatibility, enzymopathy, hemoglobinopathy a-thalassemia

  • C.Decreased production-pure red cell aplasia


Anemia Historical Factors

  • Age-Neonatal period initial manifestation of hemolytic disease, 6 m-iron deficiency, b-thalassemia

  • Ethnic group-Thalassemia syndromes, G6PD def

  • Diet- documented sources of iron

  • Drugs- oxidant-induced hemolytic anemia, drug induced aplastic anemia

  • Inheritance-family history of anemia, jaundice, gall stones


Anemia Physical Findings

SkinHyperpigmentationFanconi Anemia (FA)

FaciesFrontal bossingThalassemiaProminence malarMajor

&maxillary bone

EyesMicrophthalmiaFA

HandsAbnormal thumbFA

SpleenEnlargementHemolytic anemia, infection, leukemia


Features of Ineffective Erythropoiesis


FA Congenital Anomalies


Complete Blood Count

  • Hemoglobin

  • MCV

  • WBC and differential count

  • PLT

  • RDW- red cell distribution width

  • CHr - hemoglobin concentration in reticulocytes


Microcytic AnemiasMCV<80fl

  • Iron deficiency anemia

  • Thalassemia syndromes

  • Chronic inflammation

  • Siderblastic anemias

  • Lead poisoning


Normocytic AnemiasMCV 80-90fl

  • Congenital hemolytic anemia

  • Acquired hemolytic anemia

  • Acute blood loss

  • Splenic pooling

  • Chronic disease


Macrocytic AnemiasMCV>90fl

With megaloblastic bone marrow

  • Vitamin B12 deficiency

  • Folic acid deficiency

  • Hereditary orotic aciduria

    Without meglaoblastic bone marrow

  • Aplastic anemia

  • Pure red cell aplasia

  • Liver disease

  • Congenital Dyserythropoietic Anemia


Direct antiglobulin test (Coombs’)


Bone Marrow Aspiration


Acute Lymphoblastic Leukemia


Bone Marrow Biopsy

Normal

Aplastic anemia


Erythroid BM Colonies


Iron Deficiency Anemia in Children


Human Hemoglobin


Distribution of Iron in Man

Cytochromes 3%

Myoglobin 10%

Ferritin & Hemosiderin 22%

Hemoglobin 65%


Nutritional Iron Deficiency


Increment of RBC Mass as Function of Age


Stages of Iron Depletion


Absorption of Food Iron


Iron Absorption in Infants


Mental &Psychomotor Development According to Hb Concentration


Prevention of Nutritional Iron Deficiency Anemia

  • Encourage breast feeding for the first 6 months

  • Avoid cow’s milk at least for the first year of life

  • Iron fortified formula (12mg/l)

  • Solid food: cereals, meat

  • Oral iron 2mg/kg 4-12months

  • CBC: 9-12 months and 15-18 months


Iron Doses for Low Birth Weight Infants Starting at 1 Month of Age

IronBirth weight

mg/kg/day(g)

41000

31000-1500

21500-2500


“The tragedy of iron deficiency during infancy and early childhood”

  • Brain injury as a result of iron deficiency caused by improper nutrition

  • Iron deficiency affects mental development and motor functioning

  • Reduced activity of iron-containing enzymes in CNS, appear to be irreversible

    Buchanan G, J of Ped 135:413, 1999


Nutritional Iron Deficiency

  • No iron prophylaxis

  • No introduction of meat products

  • Increased tea consumption


Stages of Iron Depletion


Iron Depletion

  • Hb, MCV, RDW, CHr-Normal

  • SI, TIBC-Normal

  • Serum Ferritin- Low


Iron Deficiency – No Anemia

  • Hb, MCV- Normal

  • RDW- High

  • CHr- Low

  • Serum Ferritin- Low

  • Serum Iron – Low

  • TIBC- High


Iron Deficiency Anemia

  • Hb-Low

  • MCV- Low

  • RDW- High

  • CHr –Low

  • Serum Iron –Low

  • TIBC – High

  • Serum Ferritin - Low


Iron Deficiency-Biochemical Markers

  • Serum iron concentration-

    Influencedby iron absorption from meals, infection, inflammation and diurnal variation

  • Total iron-binding capacity (TIBC)-Increases in iron deficiency.

    Decrease in malnutrition, chromic infection and cancer.

  • Ferritin-Correlates with total iron stores.

    Acute phase reactant


Iron Deficiency- Serum Transferrin Receptor

  • Serum transferrin receptor- in iron deficiency there is increased number of receptors

    Unlike ferritin, increases in iron deficiency but not in chronic infection


Iron Deficiency-Treatment

  • Elemental iron 5-6mg/Kg/d

  • Reticulocytosis in one week

  • After 1 month the Hb should increase by at least 1gr%

  • Iron therapy continued 2-3 months after Hb returned to normal

  • No improvement after a month other cause for iron deficiency


Etiologic Factors in Iron Deficiency (1)

Increased physiologic requirements

  • Rapid growth

  • Menstruation

    Decreased iron assimilation

  • Iron-poor diet

  • Iron malabsorption: Celiac disease


Etiologic Factors in Iron Deficiency (2)

Blood loss

  • Gastrointestinal bleeding

  • Milk induced enteropathy

  • Peptic disease

  • Inflammatory bowel disease

  • Parasite bowel infection

    Hemoglobinuria due to prosthetic valve

    Idiopathic pulmonary hemosiderosis

    Intense exercise


Thalassemia Syndromes & Hemoglobinopathies

  • -thalassemia

  • -thalassemia

  • Sickle cell anemia


-thalassemia


Geographical Distribution of Thalassemia and Hemoglobin Disorders


Globin Synthesis in Embryo, Fetus and Adult


b-thalassemia -Location and Type of Mutations


Clinical Classification of b-thalassemia

  • b-thalassemia trait

  • Homozygous b-thalassemia Thalassemia Major Thalassemia Intermedia


-thalassemia minor


Differential Diagnosis of Microcytosis

Iron deficiencyCarriers of Anemia  Thalassemia

Serum IronLowNormal

TransferrinHighNormal

FerritinLowNormal

HemoglobinNormalHigh A2

electrophoresis


-thalassemia Minor –HPLC Hb Electrophoresis

Hb A


-thalassemia Carrier Detection

  • Microcytic anemia

  • MVC <78fl, MCH<27pg

  • HbA2>3.5%


-thalassemia Major


Thalassemia Major at Diagnosis


Peripheral Blood Smear

Normal

Beta-thalassemia Homozygote


Homozygous -thalassemia Hb Electrophoresis

Hb F


Decline in Fetal Hemoglobin


Pathogenesis of b-thalassemia Major

Free excess of a-globin chains

Hemolysis

Ineffective erythropoiesis

Severe anemia

Skeletal deformities

Increased iron absorption


Transfusion Program-Suppression of Ineffective Erythropoiesis


Clinical Manifestations of Iron Overload

  • Cardiac: arrhythmias, CHF

  • Endocrine: growth failure, delayed sexual maturation, hypoparathyroidism, hypothyroidism, DM

  • Skin: bronze discoloration

  • Liver: cirrhosis


Important studies of Deferoxamine Therapy in ThalassemiaYearFinding1974IM therapy stabilize hepatic iron 197812h portable infusion for iron balance 1981Therapy reduces hepatic iron 1985Reduction of cardiac disease in compliant patients 1989Extended survival in young patients


Compliance with DFO Treatment and Survival


Combination of L1and DFO

  • L1 not as powerful as DFO

  • Two chelators given on the same day have additive affect on urine iron loss


BMT in Thalassemia

Prognostic Criteria

  • Hepatomegaly

  • Liver fibrosis

  • Quality of iron chelation

    Prognostic Categories

  • Class I-none of the above

  • Class II One of the above

  • Class III two or three of the above


BTM Class I


Prevention of -thalassemia

  • Carrier screening

  • Prenatal diagnosis

    CVS and DNA analysis

    Pre-implantation diagnosis (PGD)

    DNA extracted form fetal erythroblasts in maternal circulation


a-thalassemia


a-globin Cluster


a-thalassemia-Abnormal Hbs

22

22

Hb Bart’s

Hb H


Gene Deletion in a-thalassemia


Hydrops Fetalis Syndrome

  • Most Hb- Hb Barts, unable to deliver O2 to tissues

  • Tissue hypoxia & anemia

    Massively enlarged palcenta

    Heart failure, edema anasarca

    Interferes with organogenesis, -congenital malformations

    Extramedullay erythropoiesis


Hydrops Fetalis Syndrome


Hemoglobin H Disease

  • Genotype --/-a

  • On cord blood: 10-20% Bart’s hemoglobin

  • Moderate microcytic anemia

  • Hb electrophoresis 5-30% Hb H


a-thalassemina Trait

  • Genotype: - -/aa, -a/-a

  • Hb electrophoresis on cord blood:

    2-10% Hb Bart’s

  • On adult blood: microcytic, with or without anemia

  • Diagnosis by exclusion of b-thalassemia minor & iron deficiency


a-thalassemia Silent Carrier

  • -a/aa

  • Hb electrophoresis on cord blood:

    traces to 2% Hb Bart’s

  • No anemia or microcytosis on adult blood


Deletions in the a-globin Gene Cluster


Categories of a-thalassemia Mutations


Non-deletion a-thalassemia Mutations

a2

aNco

aHph

aTSaudi


a-thal Trait

--/aa

-a/-a

aTa/aa

aTa/-a

Hb H Disease

--/-a

aTa/aTa

aTa/--

a-thalassemia Genotype-Spectrum


Strategy for a-thalassemia Multiplex PCR Analysis


Anemia of Chronic Infection


Anemia of Chronic Infection

  • Serum Iron- Low

  • TIBC- Low

  • Serum ferritin- High

  • Reduced release of iron form macrophages and reduced intestinal iron absorption


Anemia of Chronic Disease


  • Login