Anemia : Diagnostic

MOHAMAD YANUAR
approach ANGGARA
 • Anemia:
• The most common
problem in children
(80%)
Introduction • Most commonly,
incidental finding
• Asymptomatic 
found on routine
screening
• Consequences:
impaired growth and
development
• It is a sign, not a final
diagnosis
• Key historical points,
findings on physical
examination and
laboratory evaluation
can reveal the
underlying cause of the • Irwin, 2001
anemia
• Hermiston,Mentzer,
2002
 • For practical purposes, any of the three
concentration measurements are used to
establish the presence of anemia :
• Hemoglobin (Hb ) level (g/dl)
• Hematocrit (%)
• RBC number (1012/L)
Definition

• Wintrobe’s 2004
 Anemia Age Hb below Ht
(g/dL) below
(%)
• Reduction in the 6 mos-5 11 33
hemoglobin
concentration, yrs
hematocrit, or number
of RBC per cubic 5 yrs – 11 11.5 34
milimeter.
yrs
• WHO criteria:
12 – 18 yrs 12 36
Normal Erythropoiesis
 Increased
destruction

Decreased
Blood loss
production

Etiology
of
anemia
 Decreased production

• Drugs : TMP-sulfamethoxazole, amphotericin

B, ganciclovir, dapsone
• Deficiencies : Erythropoietin, iron, folate,
vitamin B-12
• Infection: HIV, Parvovirus B-19, Histoplasma
capsulatum
• Marrow failure/replacement: Aplastic
anemia, pure red cell aplasia, malignancy
Etiology of • Anemia of chronic disease
anemia Increased destruction or loss

• Hemolysis : TTP, G6PD, AIH

• Defect of hemoglobin : hemoglobinopathy,
thalassemia
• Defect of the red cell membrane
(spherocytosis)
• Hypersplenisme
• Acute or chronic blood loss
 Diagnostic approach

Anamnesis

Physical examination

Laboratory evaluation

Korones D, 1999
Irwin JJ, 2007
 Anamnesis

Mostly asymptomatic

Good anamnesis  to yield important clue

Korones D, 1999
Anamnesis... • Pallor
• Acute:
• Aplastic anemia
• Leukemia
• Hemolysis
• Chronic:
• Deficiency
• Thalassemia
• AIHA
• Travelling to malaria or other
infection area

• Glader B, 2004
 • Infection
• Hepatitis virus
Anamnesis...
• Severe or chronic infection  IDA,
• hemolysis, aplastic anemia

• Chronic diarrhea: Fe, folic acid, B12

absorption 

• Occult blood loss: amoeba, hook

worm

• Glader B, 2004
 Anamnesis…
 Age
Neonatal: clinically hyperbilirubinemia
Acute or chronic blood loss
Isoimunization: ABO, Rh,
Congenital infection (TORCH)
Premature or gemelli  IDA
 Baby < 6 mos:
Indonesia : IDA (38,8%)
Congenital disorder of Hb synthesis  thalassemia
 Toddler and adolescents: rapid growth,
poor intake, excessive blood loss (girl)  IDA

Korones D, 1999
Nathan-Oski, 2003
Ringo-Ringo, 2006
 Anamnesis…..

Drugs, Chemicals, Radiation

Drugs:
Sulfonamide  hemolysis
Chloramphenicol  aplastic anemia
Epileptic agent: fenitoin
Herbal

Chemical substrate or solvent

Benzene
Organophosphate HEMOLYSIS
Napthalene

Radiation  leukemia
Patients occupation, hobbies  aplastic anemia
Environmental
Glader B, 2004
Nathan oski, 2003
 Anamnesis…

 Dietary history:

1. A critical to analysis

2. Question : must be specific (meal by meal) 

quantitative information

3. PICA or dysphagia  IDA

Glader B, 2004
 Anamnesis...

 Neuromuscular feature, joint and bone pain

 Severe anemia: headache, vertigo, tinnitus, muscular
weakness, lack of concentration, etc.
 Pernicious anemia: Paresthesias with other sign of
peripheral neurophaty
 Leukemia: unexplained joint pain
 Infiltration of Neuroblastoma to medullaspinalis:
 Acute paresis or paralysis
 Gait disturbances
 Incontinencia alvi/urine

Lanzkowsky P, 1995
Glader B, 2004
 Anamnesis…..

 Bleeding:

Mucosal bleeding, petechiae, eecyhimosis, hematom or

hemarthrosis, GI track

Menometrorarghia in adolescent women

Nathan oski, 2003

Glader B, 2004
 • Mild: often not detected
on physical exam.
• Pallor :
• Hb < 7 g/dl or Ht < 25
vol %
• Difficult variations of
normal skin color
• Best detected: lips,
palmar, nail beds
Physical examination
• Attention! 3 major
symptoms:
• Pallor or anemia
• Bleeding
• Organomegaly

• Nathan-oski, 2003
• Glader B., 2004
 Physical examination...

Facies
 Frontal bossing or facies Cooley  Hemolytic anemia

Eyes
 Microcornea  Congenital aplastic anemia

 Proptosis bulbi with periorbital hematom 

Neuroblastoma
 Aniridia: Wilms tumor

 Icteric: Hemolysis or inefective erythropoesis

 Subconjunctival hemorrhage: Thrombocytopenia

Oski FA, Brugnara C, Nathan DG, 2003.

Lanzkowsky P., 1995
Proptosis bulbi with
periorbital hematom
 Physical examination...

 Skin, nail and mucosal changes

Jaundice and hyperpigmentation  Congenital aplastic anemia or

iron overload
Thinning, loss of luster, early graying hair

Stomatitis angularis, glossitis

Papil athrophy of the tounge Fe,vit B12

def.
Spoon nail, brittle and break easily

Salmon pink seborrhoic dermatitis  Langerhans cells histiocytosis

Nathan-oski, 2003
Glader B., 2004
 Papillae athrophy

Spoon nail
Salmon pink seborrhoic dermatitis
 Physical examination...

Neuromuscular feature

Severe anemia: Headache, vertigo, tinnitus, lack of

mental concentration, muscular weakness

Pernicious anemia: Paresthesias with peripheral

neuropathy

Glader B., 2004

Lanzkawsky, 1995
 Physical examination...

Gastrointestinal changes

Glossitis, papillae athrophy of the tongue  IDA or

Pernicious anemia

Ulcerative ulcer, necrotic lesions  Aplastic anemia,

acute leukemia

Dysphagia  IDA

Glader B., 2004

Lanzkawsky, 1995
 Initial evaluation

Other cell lines (ie. WBC, PLT)

decreased

Yes No

Depending on history physical + blood Evaluate by

smear indicies
Consider bone marrow exam

Microcytic Normocytic Macrocytic

Wintrobe’s 2007
Laboratory

Refining the differential diagnosis of anemia:

Use of the
CBC
RBC indices (MCV,MCH,MCHC, RDW)
Reticulocyte count
Blood smear
History and physical examination

to guide selection of further diagnostic test

Reticulocyte
 Type of Anemia
Based on the MCV
Microcytic
Microcytic Anemia (MCV< 80fl)

• Defect in the production of hemoglobin

• Differential diagnosis in pediatrics:

iron deficiency anemia (most common)
thalassemia
lead poisoning
anemia of inflammation
sideroblastic anemia (rare)

Irwin 2001
Rossbach 2005
Wintrobe’s 2007
 IDA:
• Peak prevalence: late infancy, early
childhood, adolescence
• Etiology: rapid body growth, low
levels of dietary iron, menstrual
blood loss (females)
• Th/ trial of oral iron  initial
diagnostic test  evaluation :
microcytic ▫ Response (+)
 Reticulocyte count ↑ in 5-10
anemia.... days
 Hb ↑ by 1 g/dl/month
▫ Response (-)
 Poor compliance, poor
absorption, incorrect
diagnosis, etiology still
persist
Additional test

Ferritin
Free erythrocyte protoporphyrin (FEP)
Serum iron
Iron binding capacity

To screen for IDA

Ferritin can be elevated in :

• Infection
• Inflammation
• Malignancy
Thalassemia dan Hemoglobinopati
• Most common hereditary  autosomal recessive
• Disturbance globin chain abnormal erythrocyte
• Need lifetime transfusion
• Morbidity : hemosiderosis
• Medical and social impact

WHO/Thalassemia International Federation,1994

Whetherall, Bull WHO,2001
Higgs.,Thalassemia Syndrome,2001
Modell B, Bull WHO,2008
Clinical Manifestation

Thalassemia mayor
• Severe manifestation, early onset (mostly <1 year)
• Pallor weak
• Growth and development disturbance
• Hepar and spleen enlargement
• Facies Cooley:
• Lifetime transfusion (depends on transfusion)
 Clinical Manifestation

Thalassemia intermedia
• Less Severe
• Onset later usually >2 years
• May or may not require occasional tranfusion
 Clinical Manifestation

Thalassemia minor/trait/carrier
• No clinical sign mild anemia
• No organomegaly
• Not required tranfusion
• Lab: mild anemia and hemolytic process
 Microcytic anemia...

Thalassemia minor
Difficult to differentiate with IDA

Mentzer index: (MCV / RBC)

sensitivity: 85%

< 13 : thalassemia minor

> 13 : IDA

High risk IDA adequate therapy but no improvement 

thalassemia minor, and check hemoglobin analysis

Irwin JJ., 2007

Andrews, 2004
Smith, 1996
Qurtom HA., 2004
Thalassemia trait Iron Deficiency
Normal peripheral
blood

Iron
deficiency
Thalassemia trait Thalassemia major
Normocytic
Normocytic anemia (MCV 82-97 fL)

Hemolysis :
Blood smear
Increased
Blood loss
Reticulocyte
No
count Anemia of
Bi-/
chronic
pancytopenia disease
Yes BMA Decreased
infection
(parvo-
virus,HIV)
Macrocytic
 Macrocytic anemia (MCV > 97 fL)
Evaluate smear for oval macrocytes and
hypersegmented neutrophils

absent present

Reticulocyte Decreased Megaloblastic anemia

count or normal
Check B-12/folate

increased
low normal
Medication
Liver/thyroid disease
Hemolysis
Hemorrhage idiopathic
deficiency
Hyperslenisme No Aplastic
anemia BMA
Wintrobe’s 2007
Management approach

• Depend on the underlying disease

• IDA/Thalasemia transfusion indication different

• Emergency: Hb ≤ 5 g/dl  give PRC transfusion 5

ml/kg/BW/X, then 10-15 ml/kg BW/X
• The rules: ∆ Hb X BW X 4
• Transfusion are given in multiple small volumes,
separated by several hours

• Suggested to collect blood sample before transfusion

for further laboratory examination
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