Anemia in Childhood Laura Rooms, M.D. - PowerPoint Presentation

Slide1

Anemia in Childhood

Laura Rooms, M.D.

Slide2

Definition of Anemia

Who here is anemic?

Newborn baby boy with hemoglobin 12.8 g/

dL

2 month-old baby girl with

hgb

9.5 g/

dL

4 year-old girl with

hgb

10.6 g/

dL

16

y.o

. boy with

hgb

12.8 g/

dL

g/

dL

First hint – there are two correct answers

The correct answers are A and D

Slide3

Lanzkowsky, Pediatric Hematology & Oncology, p. 753

Definition of

Anemia

Varies by age and gender

Age

Male

Mean Hgb (-2SD)

Female

Mean Hgb (-2SD)

Birth

16.5 (13.5)

16.5 (13.5)

2 months

11.5 (9.0)

11.5 (9.0)

0.5 – 2 years

12.0 (10.5)

12.0 (10.5)

2 – 6 years

12.5 (11.5)

12.5 (11.5)

6 – 12 years

13.5 (11.5)

13.5 (11.5)

12 – 18 years

14.5 (13.0)

14.0 (12.0)

18 – 49 years

15.5 (13.5)

14.0 (12.0)

Slide4

Initial Work-Up

History & Physical

Acute

decompensation

vs. chronic problem

Blood loss

Other findings (lymph nodes, spleen,

petechiae

)

Diet (milk intake)

CBC

Other cell lines (WBC, platelets

)

MCV

Slide5

Pallor

Slide6

Classifying Anemia

Pathophysiologic classification

Decreased production

Increased destruction

Size classification

Microcytic

NormocyticMacrocytic

MCV varies by age

Slide7

MCV

Macrocytic at birth (fetal hemoglobin)

By 6 months down to nadir

Minimum MCV = 70 + age

Adult normal 80-100

Age

MCV

-2 SD

Birth

108

98

2 months

96

77

0.5-2 years

78

70

2-6 years

81

75

6-12 years

86

77

>12 years

90

80

Slide8

Slide9

Slide10

Microcytic anemia

Iron deficiency anemia

Diet

history

Pica

Lead poisoning

Type of

housing

Mom’s pottery habit

Toys from China or Mexico

Thalassemia

Family history

Slide11

Case 1

21 month-old Vietnamese female

Lethargic and pale

Seen at PCP’s office with anemia

CBC – WBC 4.5K,

Hgb

4.6 g/

dL

, MCV 50

fl

, platelets 420K

Diet: white rice boiled in vegetables and then strained. Drinks approximately 1 gallon of whole milk every 2 days.

Slide12

Peripheral blood 50X

Slide13

Peripheral blood 100X

Slide14

Iron deficiency anemia

Preventable disease

Discuss diet with your patients

Treatment

Avoid transfusion if clinically stable

Iron supplementation 6 mg/kg elemental iron divided TID until hemoglobin normal, then 2 mg/kg/day as preventive dose

Reticulocyte count should increase in a few days, hemoglobin within a week

Number one reason for treatment failure - noncompliance

Slide15

Iron deficiency anemia

Confirmatory tests

Serum iron (low)

Total iron binding capacity (high)

Transferrin saturation = serum Fe/TIBC (<16%)

Ferritin should be low but could be high (acute phase reactant)

Long term effects

Psychomotor developmental defects

Impaired educational performance

Impaired endurance

Slide16

Lead poisoning

Can’t differentiate from iron deficiency by CBC

Lead level on children at risk

Older homes

Pica

Symptoms of lead poisoning (usually subclinical)

Acute encephalopathy (seizures to coma)

Chronic encephalopathy (behavior changes, malaise) with abdominal pain and vomiting

Slide17

Thalassemia

Mutation in hemoglobin chain resulting in low or absent hemoglobin production

Range from asymptomatic trait to thalassemia major

Microcytic anemia with high RBC

Diagnosis – hemoglobin electrophoresis (

neonatal available and better for alpha

thal

trait)

Two types

Alpha thalassemia

Beta thalassemia

Slide18

Thalassemia

Slide19

Alpha Thalassemias

Alpha genes deleted

Clinical disorder

Newborn Hb

(Hb Barts = gamma tetramer)

Adult Hb

(Hb H = beta tetramer)

One

None

1-3%

0%

Two

Thal minor

4-10%

0%

Three

Hb H disease

15-25%

10-25%

Four

Fetal death

100%

N/A

Slide20

Beta Thalassemia

Beta Thalassemia type

Heterozygote

Homozygote

β

o

(mutation results in no beta chain production)

Thal minor

Hb A2 3.5-8%

Hb F 1-5%

Thal major

Hb A 0%

Hb A2 2-10%

Hb F 90-98%

β

+

(Mediterranean)

(point mutation results in unstable beta chain)

Thal minor

Thal major

Hb A 5-30%

Hb A2 2-5%

Hb F 70-90%

β

+

(African American)

(point mutation results in unstable beta chain)

Thal minor

Thal major

Hb A 5-75%

Hb A2 2-5%

Hb F 20-40%

Slide21

Thalassemia Major

Severe anemia, dependent upon transfusions

Poor growth

Expansion of bone marrow – frontal bossing, etc.

Extramedullary hematopoiesis – hepatosplenomegaly

Develop iron overload

Slide22

Slide23

Macrocytic Anemia

B12 or folate deficiency

Inborn errors of metabolism

Hypothyroidism

Liver disease

Down syndrome

Fanconi anemiaElevated reticulocytosis following anemia of acute onset

Slide24

Macrocytosis

Slide25

Hypersegmented Neutrophil

Slide26

Case 2

8 year-old boy referred by his PCP due to pancytopenia

PE – short stature, digitalized thumb, scars on abdomen

PMH – gastroschisis at birth resulting in short gut syndrome (basically no ileum), had been on TPN and vitamin B12 supplements, but not for last several years

CBC – WBC 1.7, Hb 3.2, MCV 103, plt 106

Slide27

Case 2, cont.

Transfused with packed red blood cells

Bone marrow aspirate and biopsy done – hypercellular with megaloblastoid erythroid precursors.

Chromosomal fragility normal

Responded fully to vit B12 IM, then maintained on B12 “dots”

Slide28

Slide29

Normocytic Anemia

This is where it gets difficult!

Obtain a reticulocyte count

High – increased

destruction or loss

Low or normal – poor production

Check a bilirubin

Normal

bilirubin

Blood loss

High bilirubin

Hemolysis

Slide30

Decreased Production

Decreased reticulocyte count

Low WBC/platelets

Infiltrated marrow

Congenital aplastic anemia

Acquired aplastic anemia

Bone marrow suppression from infection (viral)

Normal WBC/platelets

Diamond-

Blackfan

anemia

Transient erythroblastopenia

of childhoodAplastic crisis in patient with underlying hemolytic anemia

Slide31

Diamond Blackfan Anemia

“Congenital” aplastic anemia

Presents in first 5 years of life

Often responds to steroids

Slide32

Case 3

17 month-old girl had viral illness 2 weeks ago. Presents to PCP with lethargy and waxy appearance.

PE – pallor, no HSM or LAD

CBC – WBC 10.3,

Hb

5.6, MCV 80.9, platelets 660,

retic

0%

Transfused with PRBC’s, a few weeks later

retic

count increased to 7% and her

Hb normalized.

Slide33

Hemolytic anemias

Positive Coombs’ test – extrinsic causes

Autoimmune hemolytic anemia

Isoimmune hemolytic anemia

Negative Coombs’ test

Hemoglobinopathy

Enzymopathy

RBC membrane disorders

Intravascular hemolysis

Slide34

Hemoglobinopathies

Sickle cell disease

Types

Hemoglobin SS (65-70%)

Hb

SC

Hb

S

β

(0 or +)

Others

Signs and symptoms

In first year of life –

dactylitis

, splenomegaly

After – complications such as pain crisis, acute chest

Diagnosis – hemoglobin

electrophoresis (newborn screen)

and RBC morphology

Slide35

Sickle cell disease

Slide36

Enzymopathies

G6PD deficiency

Hemolytic crisis following ingestion of triggers

Fava beans, antimalarials, sulfonamides, nitrofurantoin, aspirin, antihelminthics, methylene blue, etc.

X-linked recessive

10% of African American population

Confirmed with G6PD levels

Pyruvate kinase deficiency

Chronic hemolysis with splenomegaly

Splenectomy ameliorates symptoms

Confirmed with PK levels

Slide37

RBC Membrane Disorders

Hereditary spherocytosis

Presents in the neonatal period with jaundice and anemia

Autosomal dominance – often a positive family history of anemia, jaundice, gallstones, splenectomy

Diagnosed by morphology, confirmed by osmotic fragility

Ameliorated with splenectomy

Other rarer disorders – elliptocytosis, pyropoikilocytosis, stomatocytosis, acanthocytosis, xerocytosis

Slide38

Case

4

9 y/o WM referred for evaluation of anemia

7 day h/o febrile illness with occassional emesis

Seen on day of illness #3 where CBC showed anemia.

PCP follow up confirmed anemia

+ exercise intolerance. Improving energy level.

No URI symptoms. Negative Strep swab.

PMH: negative for jaundice as a newborn. + allergies. Normal development

Slide39

Case

4

continued

FMH: H/O jaundice as a newborn in mom and maternal GM. + gallbladder disease on both sides. No known h/o anemia. HTN, DM, Colon CA, mental illness.

ROS: Headache, arm and leg pain, poor appetite

PE: Slight pallor. No HSM. Normal VS’s. No LAD

Slide40

Case

4

continued

Lab:

5/6

(day of illness #3)

WBC=3.2; Hgb=7.7; Hct=22; plt=68

5/7

WBC=5.3; Hgb=10.3; Hct=28; plt=259

5/10

WBC=8.2; Hgb=9.8; Hct=26; plt=447Retic = 4Coombs’ Negative

Slide41

Peripheral Smear

Slide42

Intravascular (extracorpuscular hemolysis)

Idiopathic

Secondary

Drugs

Infection (DIC)

Microangiopathic

(e.g. TTP, HUS)

Waring

blender morphology

Slide43

TTP

Peripheral smear

Slide44

TTP Peripheral

smear

Slide45

Cases to Work Out If Time Permits

Slide46

Extra Case 1

8

y.o

. girl, AA from Lawton

Presented to ER at Reynolds with pain in chest and legs – exam unremarkable

History of multiple episodes like this, often

preciptitated

by swimming

WBC 6.6K,

Hgb

6.9 g/

dL, plt

183KMCV 79Retic 2.5%, bilirubin 1.3History of sickle cell trait on newborn screen

Slide47

Extra Case 1

Transfused up when hemoglobin dropped to 5.9 g/

dL

Pain improved with transfusion

Prior to transfusion drew

haptoglobin

and electrophoresis

Haptoglobin

normal

Hemoglobin electrophoresis

Hgb

A 13.7%

Hgb A2 6%Hgb S 67.7%Hgb F 12.6%

Slide48

Diagnosis –

Hemglobin

S-

β

+

thalassemia

Slide49

Extra Case 2

1

y.o

. boy presents from WIC with a low hemoglobin

Exam – normal, mixed race, active boy

Repeat the CBC

WBC 4.8,

Hgb

7.2 g/

dL

, platelets 302KMCV 50.8 fL

Retic – 0.2%Your next step?

Slide50

Extra Case 2

RTC in 1 week

CBC virtually identical,

retic

0.4%

RTC in 1 month

Hgb

6.2 g/

dL

,

retic

0.5%Refractory to iron?Iron deficiency or something else?

Slide51

References

Khan, L. Anemia in Childhood.

Pediatr

Annals. 2018, Feb

1;47(2

):

e42-e47.

Yawn,BP

et al. Management of sickle Cell Disease: summary of the 2014 evidence-based report by expert panel members. JAMA.

2014 Sep 10;312(10):1033-48

.

 Wang, M. Iron Deficiency and other types of anemia in infants and children. Am Fam Phys

2016 Feb 15;93(4):270-8.Nathan and Oski's Hematology of Infancy and Childhood - 7th Edition