CHILD WITH ANEMIA

DEFINITION

HB below normal range

NEONATE <14g/dL

1-12 MONTHS < 10g/dL

1-12 YEARS < 11 g/dL

HISTORY
 Age of onset
 Newborn: hemorrhage, hemolysis, infections, impaired RBC productions
 Infants & children: IDA, vitamin B12 deficiency, hemolytic anemia
 Adolescent, menstruating & pregnant teens: IDA

 Sex
 X-linked disease: G6PD deficiency

 Inheritance/Genetics
 Autosomal dominant: spherocytosis
 Autosomal recessive: sickle cell, thalassemia, Fanconi anemia
 Family member with early age of cholecystectomy/splenectomy
 History of gallstone, recurrent jaundice, blood transfusions
 Diet
 Poor feeding, improper time and quality of weaning food
 Cow’s milk diet & Breast milk (BF): IDA
 Strict vegetarian: Vit B12 deficiency
 Goat’s milk: folate deficiency
 Pica: IDA

 Drugs
 G6PD: oxidants (sulfa, primaquine, henna)
 Immune mediated hemolysis: penicillin
 Bone marrow suppression: chemotherapy
 Phenytoin increase folate requirement

 Infections/infestations/travel hx
 Giardia: iron malabsorption
 EBV, CMV, parvovirus: bone marrow suppression
 Mycoplasma, malaria: hemolysis
DIAGNOSTIC APPROACH TO ISOLATED ANEMIA IN
CHILDREN: MORPHOLOGIC CLASSIFICATION
LOW MCV
NORMAL MCV
Low/normal
reticulocyte count
High reticulocyte
count
IRON DEFICIENCY ANaEMIA
Etiology

• Chronic blood loss

• Increase iron demand- prematurity and growth
• Inadequate intake
• Malabsorption
• Worm infestation
SYMPTOMS AND SIGNS

• Failure to thrive
• Fatigue/lethargy
• Pica
• Poor feeding
• Rapid breathing
• Pallor
• Angular stomatitis
• Koilonychia
LABORATORY FINDINGS

• Low haemoglobin
• Low MCV, Low MCH (hypochromic, microcytic anemia)
• Low serum iron
• High TIBC
• Low serum ferritin
• Increase RBC distribution width
TREATMENT
• Nutritional counselling
-if breast fed, maintain breastfeeding
-use iron fortified cereals
• Oral iron medication
-6mg/kg/day of elemental iron
-continue for 6-8 weeks after HB is restored to normal
-dose calculation depends on the elemental iron in the preparation
• Syrup FAC: the content of elemental iron per ml depend on the preparation available. (usually
86mg/5ml)
• T. ferrous fumarate 200mg has 65mg of elemental iron per tablet
• Consider of this following if failure to response to oral iron
-non compliance
-inadequate iron dosage
-unrecognized blood loss
-impaired GI absorption
-incorrect diagnosis
-Iron Resistant Iron Deficiency Anaemia
Blood Transfusion

• NOT required in chronic IDA unless patient is:

-in overt cardiac decompensation
-severely symptomatic (FTT, poor weight gain)
• In patient with chronic anaemia. Safe to plan the transfusion the next morning (during
working hours) and take necessary blood investigation prior to transfusion (FBP, Hb analysis,
HIV etc.)
• In severe anaemia (Hb <4g/dl) low volume RBC (<5mls/kg) is preferred. It might be
necessary to transfuse slowly over 4-6hours with IV Frusemide (1mg/kg) midway.
THALASSEMIA
 INTRODUCTION
WHAT IS THALASSEMIA?

Thalassemia is a group of hemoglobin disorders in which the production of

normal hemoglobin is partially or completely suppressed as a result of a
defective synthesis of one or more globin chains.

Thalassemia is inherited by autosomal recessive

Fe (iron deficiency anemia)

Heme
Protophorphyrin (sideroblastic anemia)
Hemoglobin
Globin (thalassemia)
INTRODUCTION
 HEMOGLOBIN
The oxygen carrying capability of the red blood cells (RBCs) relies on hemoglobin, a tetramer protein
that comprises 4 globin chains bound to the heme molecule.
There are 4 major types of globins: alpha (α), beta (β), gamma (γ), and delta (δ).

HEMOGLOBIN A
 2α and 2β chains forming a tetramer
α β
 97% of adult hemoglobin
 Post-natal life, HbA replaces HbF by 6 months α β

HEMOGLOBIN A2
 2α and 2δ chains δ
α
 1.5 to 3% of adult hemoglobin
α δ

HEMOGLOBIN F
 2α and 2γ chains
 1% of adult hemoglobin α γ
 70 – 90% at term and falls to 25% by first month and progressively
α γ
 THALASSEMIA

1. Silent carrier
2. Trait (minor)
α 3. HbH Disease (Intermediate)
4. Hb Bart’s (Major)

THALASSEMIA

1. Trait (minor)
β 2. Intermedia
3. Cooley’s anemia (Major)
  -THALASSEMIA
-thalassemia

 Gene deletion
 Deficient / absent of alpha subunits
o Excess beta subunits
o Excess gamma subunits in newborns

 Encoding genes on chromosomes 16

 Has 4 copies of the alpha globin gene where each gene is responsible for ¼
production of alpha globin
  -THALASSEMIA
CLASSIFICATIO
N

CLASSIFICATIO N GENOTYP E NO.OFGENESPRESENT

Silent carrier   /- 3
α-thalassemia trait - /- or   / - - 2
Hemoglobin H - /-- 1
Hb Bart’s / Hydrops fetalis --/-- 0

norma l silentcarrie r Hemoglobin H

α -thalassemiatrait H b Ba r t ’ s/ H y d r o p s f e t a l i s
 CLINICAL OUTCOMES OF
 -THALASSEMIA
SILENTCARRIERS
 Asymptomatic

-THALASSEMIA MINOR (TRAIT)

 No anemia
 Microcytosis

-THALASSEMIA INTERMEDIA (HE

 Anemia and microcytosisM O G L O B I N H)
 Bone deformities
 Splenomegaly
 CLINICAL OUTCOMES OF
 -THALASSEMIA
HEMOGLOBIN C O N S TA N T SPRING
 Similar to HbH but no microcytosis
 Anemia
 Growth delay

-THALASSEMIA MAJOR
 Hemoglobin Bart’s
 Fatal hydrops fetalis
 β -THALASSEMIA
β- t h a l a s s e m i a

 Gene mutation
 β0 refers to the complete absence of production of β-globin
on the affected allele
 β+ refers allele with some residual production of β-globin
(around 10%)

 Encoding genes on chromosomes 11

 Synthesis of β-globin is controlled by 2 genes

β -THALASSEMIA
 β -THALASSEMIA
CLASSIFICATION
An a b se n c e o r d e f i c i e n c y o f β c h a i n sy n t h e si so f a d u l t H b A

β- t h a l a s s e m i a m i n o r
Loss of ONE gene – thalassemia minor trait

β- t h a l a s s e m i a m i n o r
Loss of BOTHS genes – thalassemia intermedia and major
 β+β+ or β0β+ (thalassemia intermedia)
 β0β0 (thalassemia major)

β β β β+
β+ β+ β0 β + β0 β0

Norma l Minortrai t Intermedi a

Major
 DIAGNOSTIC CRITERIA

CLINICAL FEATURES LABORATORY FEATURES

 Hb : < 7 g/dL
THALASSEMIA  Anemia  HbF: > 90%
 Hepatosplenomegaly HbA2: normal or high
MAJOR  Growth failure

 HbA : usually absent

 Hb : < 8-10 g/dL

THALASSEMIA  Milder anemia  HbF: > 10%
 Thalassemia facies HbA2: 4-9%, if > 10% suggests HbE
INTERMEDIA  Hepatosplenomegaly

 HbA : 5-90%

 Hb : < 10 g/dL
 MCH : < 27 pg
 THALASSEMIA  Normal to mild anemia  HbF: > 2.5-5%
 No organomegaly  HbA2: 4-9%, if >20% suggests HbE
TRAIT
trait
 HbA : > 90%
 APPROACH
 Symptoms of anemia
 Positive family history
 History of blood transfusion
 Failure to thrive
History taking

Features of
1. Severe anemia
2. Ineffective erythropoiesis
3. Extra medullary
Physical findings hematopoiesis
4. Iron overload resulting
from transfusion and
increased iron absorption.
5. Complications

Lab investigations
CLINICAL PRESENTATION
THALASSEMIAMINOR

 Usually asymptomatic / mild pallor

 May present as iron deficiency anaemia (hypochromic
microcytic anaemia)
 Mild persistent anemia not responding to hematinic
 Normal life expectancy
CLINICAL PRESENTATION
THALASSEMIAMAJOR

GENERALFEATURES EXCESSIVEERYTHROPOEISIS

 Pallor  Maxillary overgrowth (chipmunk)

 Fatigue  Increased spaces, overbite and
 Dyspnea on exertion malocclusion of teeth
 Poor apetite  Frontal bossing
 Palpitations  Chronic sinusitis
 Poor growth  Impaired hearing

F E A T U R E S O F H E M O LY S I S
 Jaundice
 Hyperuricaemia (Gout)
 Gallstones
CLINICAL PRESENTATION

EXCESSIVEERYTHROPOEISIS

BONECHANGES EXTRAMEDULLARY

 Medullary expansion – cortical  Hepatomegaly

thinning, risk of pathological  Spleenomegaly
fracture
 Bone pain, backache
 Vertebral expansion lead to spinal
cord compression – neurological
manifestations
CLINICAL PRESENTATION
IRON OVERLOAD

ENDOCRINEFAILURE CARDIACINVOLVEMENT

 Short stature  Arrhythmia

 Delayed puberty  Cardiomyopathy
 Estrogen / testosterone deficiency  Pericarditis
 Diabetes mellitus  CCF
 Hypoparathyroidism

HEPATIC INVOLVEMENT HYPERCOAGULABLEDISEASE

 Cirrhosis  Deep vein thrombosis
 Hepatic fibrosis  Pulmonary embolism
CLINICAL PRESENTATION
 DIAGNOSIS

DIAGN OS I S I S BAS E D ON :
i. Clinical features
ii. Lab investigations
iii. Screening family members

AIM S OF IN VESTIGATION S

i. Confirm the diagnosis

ii. Exclusion of other differential diagnosis
iii. To find the cause of anemia
iv. To assess the complications
v. For further management
A LG O R I T H M F O R SCREENING OF
T H A L A S S E M I A IN MALAYSIA

Screening blood test (FBC/ RBC

indices)

Suspected thalassemia
Normal
carrier

Confirmatory blood test

Normal THALASSEMIA CARRIER

For family screening

 LABORATORY FINDINGS

 Normal red blood cells

 They have a zone of central pallor about 1/3 the size of RBC
 RBC’s demonstrate minimal variation in size (anisocytosis) and shape (poikilocytosis)
 A few small fuzzy blue platelets are seen
 In the center of the field are a band neutrophil on the left & a segmented neutrophil
on the right
LABORATORY FINDINGS
LABORATORY FINDINGS

 Smaller size of RBC

 Increase zone of center pallor
 Indicative of hypochromic and microcytic anemia
 Increase anisocytosis and poikilocytosis
LABORATORY FINDINGS
LABORATORY FINDINGS
LABORATORY FINDINGS
LABORATORY FINDINGS
BASELINE INVESTIGATIONS
BASELINE INVESTIGATIONS
FULL BLOUD COUNT/PERIPHERAL BLOOD FILM

H B A N A LY S I S / H I G H P E R F O R M A N C E L I Q U I D C H R O M AT
OGRAPHY (HPLC)

SERUM FERRITIN

RED CELL PHENOTYPING

D N A A N A LY S I S

LIVER FUNCTIONTEST

INFECTION SCREEN

HLA TYPING
 INVESTIGATIONS
E XC LU S I O NO F O T H E R D I F F E R E N T I A L DIAGN
OSIS

IRON STUDIES
 To distinguish mild microcytic anemia due to -thalassemia carrier state from any
other causes
 Iron studies are useful in excluding iron deficiency and the anemia of chronic
disorders as the cause of patient’s anemia

MENTZERINDE
X
 Calculation of Mentzer index (mean corpuscular volume per red cell count) may be
helpful
 <13 suggests patient has thalassemia trait
 >13 suggests patient has iron deficiency
Management of
thalassemia
REGULAR BLOOD TRANSFUSION and

IRON CHELATION THERAPY is the mainstay of

treatment with trafusion dependant thalassemia
MAINTAINANCE OF BLOOD
TRANSFUSION
BETA THALASSEMIA MAJOR
WHEN TO START TRANSFUSION
- AFTER mandatory blood investigations already taken for diagnosis confirmation. In
emergency cases no need to wait for the result BUT blood investigations MUST be taken
before transfusions
-Hb analysis + infection screening + RBC phenotype must be DONE prior to transfusion as it will
affect subsequent result and management
THALASSEMIA MAJOR
-Once diagnosis is confirmed
-Hb < 7g/dl on 2 occasions > 2 weeks apart (in absence of other factors)

THALASSEMIA INTERMEDIA
-Hb <8g/dl if theres evidence of impaired growth attributed to anemia

-Bone changes (maxillary/mandibular prominence),

enlarging liver and spleen, para spinal masses
TRANSFUSIONS TARGET
• Maintain pre transfusion Hb level at 9 -10 g/dl.

• Keep mean post-transfusion Hb at 13.5-15.5g/dl.

• Keep mean Hb 12 - 12.5 g/dl.

• These will allow normal physical activities and growth, no chronic

hypoxemia and reduces compensatory marrow hyperplasia which causes
irreversible bone changes, para spinal masses
 TRANSFUSIONS INTERVAL
- Usually 4 weekly interval (usual rate of Hb decline is at 1g/dl/week).
- Depending on patients (3-6 weekly)
TRANSFUSIONS VOLUME
-Volume to transfuse: (13-current Hb) x 4 x weight
-Example:
Hb 7, weight 90kg
(13-7) x 4 x 40
= 960mls
-Minimizes number of immunological unit of blood avoid wastage of donated blood
Thalassemia intermedia
-Clinical diagnosis presents with less severe anemia at more than 2 years age
-Symptom varies
-All mandatory blood investigation pre transfusion must be taken like transfusion dependent
anemia patients
Alpha thalassemia trait hb h disease
Transfuse only if hb less than 7g/dl or symptomatic
IRON CHELATION THERAPY
- To prevent iron overload in transfusion dependent thalassemia
-compliance to treatment may have better outcome, up till 6th decade

DESFERRIOXAMINE / DFO (DESFERAL) - SUBCUTANEOUS

DEFERIPRONE / DFP / L1 (FERRIPROX/KELFER) – PER ORAL
DEFERASIROX / DFX (EXJADE) – PER ORAL
 DESFERRIOXAMINE (DESFERAL)
When to start Age > 3 years old.
Serum ferritin reaches 1000 μg/L.
Usually this is after 10 – 20 blood transfusions.

Dosage and route

Average daily dose is 20 – 40mg/kg/day.
By subcutaneous (SC) continuous infusion using a portable pump over
8-10 hours daily, 5 - 7 nights a week.

Aim to maintain serum ferritin level below 1000 μg/L.

Is given together with Vitamin C, which augments iron excretion with Desferal®.
Severely iron overloaded patients require longer or continuous SC or IV infusion of
Desferal® (via central line if necessary).
Local skin reactions usually due to inadequately diluted Desferal® or infection
Yersinia infection: presents with fever, abdominal pain and diarrhoea.
Treatment:
◦ Withold Desferal®
◦ Treat with cotrimoxazole, aminoglycoside or 3rd generation cephalosporin.

Desferal® toxicity (if using high doses > 50mg/kg/day in the presence of low serum ferritin in children):
Ocular toxicity: reduced vision, visual field defects, night blindness; reversible
Auditory toxicity: high tone deafness. Not usually reversible
Skeletal lesions: pseudo rickets, metaphyseal changes, vertebral
growth retardation.
Oral iron chelator
DEFERIPRONE/ L1
(FERRIPROX/KELFER)
Is an alternative if iron chelation is ineffective/inadequate
despite optimal Desferal® use, or if Desferal® use is
contraindicated.

No formal evaluation in children < 10 years of age.

Deferiprone is given 75 – 100 mg/kg/day in 3 divided doses.

It can also be used in combination with Desferal®, using a lower
dose of 50mg/kg/day.

There are risks of GI disturbance, arthritis and rare occurrence

of idiopathic agranulocytosis.

Weekly full blood count monitoring is recommended. Stop if

neutropenic (<1,500/mm³).
Oral iron chelators
DEFERASIROX (EXJADE)
Can be used for transfusional iron overload in patients 2 years
or older.

Dose: 20-30 mg/kg/day in liquid dispersible tablet, taken once

daily.

Adverse effects: transient skin rash, GI disturbance and a

reversible rise in serum creatinine. Monthly monitoring of
renal function is required.
COMPLICATIONS OF CHRONIC
IRON OVERLOAD

ENDOCRINE CARDIAC HEPATIC

• Endocrine: growth retardation, impaired glucose tolerance, pubertal
delay, hypothyroidism, hypoparathyroidism and diabetes mellitus.

• Cardiac: arrhythmias, pericarditis, cardiac failure.

• Hepatic: liver cirrhosis (especially if with Hepatitis B/C infection).

 Monitoring thalassaemia patient
Pubertal and sexual
During admission Annually Infection screening Bone
development
• Clinical • Growth and • Tanner staging • Viral screening • Osteoporosis
assessment development • FSH,LH • vdrl • Skeletal
• Blood ix • Endocrine • Estradiol, abnormalities
testosterone

Cardiac assessment Evaluate iron status Liver iron

assessment
• annual • Serum ferritin • Liver T2* MRI
echo/ecg • Iron studies • Liver biopsy
• Cardiac T2* • Assessment of
MRI hepatitis
During admission for blood transfusion
• Clinical assessment: height, weight, liver & spleen size, any adverse side
effects of chelation therapy.
• Pre-transfusion Hb, platelet count and WBC (if on Deferiprone).
• Post transfusion Hb – ½ hour post transfusion.
• Calculate the volume of pure RBC transfused based on the haematocrit
(HCT) of packed red blood cells (PRBC) given (usually HCT of PRBC from
blood bank is > 50 - 55%).
• Volume of pure RBC transfused = volume of blood given x HCT of PRBC
given (e.g. 600 mls x 0.55 = 330 mls).
• Iron balance assessment.
• Review of current medications.
Every 3- 6 months
Evaluate growth and development.
Serum ferritin.
Liver function test.
6 monthly
Viral screening – Hepatitis B and C, HIV, VDRL
Every year or more frequent if indicated
• Evaluate growth and development
• Endocrine assessment – modified GTT, T4/TSH, Ca, PO4
(If Ca low - check PTH & Vit. D).
• Pubertal and sexual development from 10 years onwards.
• Tanner stage of breast and genitalia.
• Follicle stimulating hormone (FSH), luteinizing hormone (LH) levels,
oestradiol or testosterone hormone levels.
• Annual volume of pure red blood cell transfused/median body weight.
• Evaluate iron balance and overload status.
• Bone: osteoporosis & skeletal abnormalities.
Cardiac assessment at variable intervals and especially after 10 years of age

• Yearly ECG or Holter monitoring for arrhythmias.

• Annual cardiac echocardiography.

• Cardiac T2* MRI.

Liver iron assessment

• Liver T2* MRI for non-invasive assessment of liver iron.

• Liver biopsy for liver iron concentration
◦ Assessment of hepatitis, fibrosis or cirrhosis in selected cases
Splenectomy
Indicated when there is evidence of hypersplenism
◦ Defined by blood consumption of vol RBC > 1.5x normal or >200-220mls/kg/year in patients > 5years of
age to maintain average hb levels

Pneumococcal and HIB vaccine 4-6w prior to surgery

Meningococcal vaccine required in endemic areas
Penincillin prophylaxis for life after splenectomy
Low dose aspirin 75mg od if thrombocytosis > 800,000mm3 after splenectomy
Diet and supplements
Oral folate at minimum 1 mg daily may benefit most patients.
Low dose Vitamin C at 3 mg/kg augments iron excretion for those on Desferal only.
Dose: <10 yrs, 50mg daily; >10yrs, 100mg daily
Give only on Desferal days
Avoid iron rich food such as red meat and iron fortified cereals or milk.
Drinking tea is advised as it may help decrease intestinal iron absorption.
Dairy products are recommended as they are rich in calcium.
Vitamin E (antioxidant),Calcium and zinc supplement recommended
Bone marrow transplantation (BMT)
Potential curative option when there is an HLA-compatible sibling marrow donor.
The results from unrelated donor or cord blood transplant are inferior compared to matched
sibling bone marrow transplant with higher morbidity, mortality and rejection rates.
Classification of patients into Pesaro risk groups based on the presence of 3 risk factors:
◦ hepatomegaly > 2cm,
◦ irregular iron chelation
◦ presence of liver fibrosis.

Best results if performed at the earliest age possible in Class 1 patients

ANTENATAL DIAGNOSIS
THRU CHORIONIC VILLOUS SAMPLING AT 9-11 WEEKS GESTATION
PATIENTS/PARENTS SUPPORT
GROUP
SUPPORT AND EDUCATION FOR FAMILIES
CAMPAIGNS