APPROACH TO

ANEMIA

Moderator: Lt col Madhuri Kanitkar

Introduction
 Defined as reduction in Hemoglobin
concentration, hematocrit or number of red
blood cells per cubic mm
 Lower limit of normal range at 2 sd below
the mean for normal population
 2.5 % of normal population mistakenly
classified as anemic.

Nathan and Oski,s Hematology of Infancy and Childhood, 5th Edn

Physiological Classification
 1. Disorders of effective red cell
production
 2. Disorders of increased red cell
destruction or loss
Ineffective red cell production
 Marrow failure
 AplasticAnemia
 Pure red cell aplasia
 Marrow replacement (Malignancy)
 Osteopetrosis
 Myelofibrosis
 Chronic renal disease
 Vitamin D deficiency

 Infection (Tb)
Ineffective red cell production
 Impaired erythropoietin production
 Chronic renal disease
 Hypothyroidism, Hypopituitarism

 Chronic inflammation

 Protein malnutrition

 Hb mutants (decreased affinity for oxygen)

Ineffective red cell production
 Abnormalities of cytoplasmic maturation
 Irondeficiency
 Thalassemia syndromes

 Sideroblastic anemias

 Lead poisoning
Ineffective red cell production
 Abnormalities of nuclear maturation
 VitB12 def
 Folic acid def

 Thiamine responsive megaloblastic anemia

 Hereditary abnormalities in folate metabolism

 Orotic aciduria
Ineffective red cell production
 Primary dyserythropoietic anemias
 Erythropoietic Protoporphyria
 Refractory sideroblastic anemia
Increased red cell destruction/loss
 Defects of hemoglobin
 Structural
mutant (HbSS, HbSC)
 Diminished globin production (Thalessemia)

 Defects of red cell membrane

 Defects of red cell metabolism
 Antibody mediated
 Mechanical injury to RBC
 HUS

 TTP

 DIC
Increased red cell destruction/loss

 Thermal Injury
 Oxidant induced red cell injury
 PNH
 Hypersplenism
 Acute/Chronic blood loss
 Plasma lipid induced abnormalities of red
cell membrane
D/D of Anemia
 History
 Physicalexamination
 CBC including retic count
 PBS
History
 Relative frequency of various causes of anemia
with age
 Maternal History
 Pregnancy/delivery complications, drug ingestion, Pica
or anemia
 Family History
 Ethnicity, Anemia, Jaundice, Splenomegaly, Gallstones,
Bleeding disorder, Cancer, Transfusions
 Patient history
 Hyperbilirubinemia, Prematurity, Diet history,
Medications, Activity level, Acute infection, Chronic
disease, Endocrinopathy, Liver disease, Easy
bruising/blood loss
Physical examination
 Heart rate
 Pallor, Cyanosis, Pedal edema,
Lymphadenopathy, Icterus
 Patechial/Echymotic spots
 Hepatosplenomegaly
 Evidence of failure
 Anemia
With Patechiae
LNpathy
No lymphadenopathy/Hepatosplenomegaly
HepatoSplenomegaly
No patechiae/ With
Echymosis With Patechiae Hepato
splenomegaly

Aplastic anemia
Nutritional
Bleeding disorder
Iron def
Coagulation disorder Thal
Megaloblastic
ITP Hbpathies
Pure red cell aplasia
DIC Liver disorders
Thal trait
Red cell enzyme def
Lead poisoning
Renal disease Leukemias
Myeloproliferative disorders
Infectios
Infiltrative disorders
DIC
CBC & PBS
 1. Compare Patients Hb and hematocrit
with normal values for age and sex
 2. Evaluate red cell indices, MCV most
important (only red cell index measured by
electronic counter)
 In < 10 yr, lower limit of MCV 70fL + age
in yrs, Upper limit 84 + 0.6 fL/Yr
 3. MCHC >35g/dl (Spherocytosis),
 Low value mostly Iron def
 4. RDW
 5. RBC count
 6. WBC count/ Platelets
 7. Leucoerytroblastic blood picture
 8. Central pallor
 Absent in Spherocytosis
 9.Distinct shape of RBCs
 10. Presence of inclusions and nucleated
RBCs
 Basophilic stippling in Thal and lead poisoning
Microcytic anemia
 Defect
in Heme / globin synthesis
 Heme synhesis
 Inadequate quantity of substrate
 Inability to use substrate

 Globin synthesis
 Inherited hemoglobinopathy
4 main D/Ds
 Irondef
 Lead poisoning
 Thalassemia
 Anemia of inflammation
 Iron def Anemia
 Age of Pt
 Diet history
 Therapeutic trial of oral iron appropriate
diagnostic test
 Iron dose 6mg/kg/d
 Fe Sulphate most bioavailable but Fe gluconate
more palatable
 Retic count should rise in 5 to 10 days
 Hb should rise by 1gm/dl/wk thereafter

PCNA,Pediatric hematology/Oncology. Part I, Oct 2002, 877-891

Clues of D/Ds other than Iron def

 No history suspicious of Iron deficiency

anemia
 Severe anemia
 Atypical hematological findings
 Age < 6 mo or >18 Mo
 No response to initial trial of Iron therapy
 Microcytic anemia D/D
 Ethnicity
 RBC count >5 lakh/dl in Thal, < 1.5 in Iron def
 RDW : High in Iron def, N in Thal trait
 Mentzer index <13 in thal trait, >14 in Iron def
 For same level of anemia
 Greater poikilocytosis, target cells and basophilic
stippling in thal
 Greater anisocytosis and more decline in MCV in Iron
def
Retic count
 Normal absolute reticulocyte count 50000 to 100000
 Retic count decreased in disorders of heme synthesis
 Iron def, Lead poisoning, anemia of chronic inflammation
 Retic count increased in disorders of globin synthesis
 Hemoglobinopathies
Microcytic anemia D/D
 Ferritin
 Low in iron def (<10 microgram/dl)
 N in thal

 N to high in lead poisoning

 High in anemia of chronic inflammation

 Retic Hb content
 Sensitive indicator of Iron def
 Lead level
Microcytic anemia D/D

 Free Erythrocyte Protoporphyrine(FEP)

N in Thal
 Increased in Iron def and Lead poisoning

 LDH, Bilirubin
 ESR
 Increased in anemia of chronic inflammation
 Hb Electophoresis
 Should not be Iron deficient at the time of
electrophoresis as Iron def depresses delta
globin synthesis obscuring a rise in HbA2
 Elevated MCV
Inceased Paucity of
reticulocytosis Reticulocytes
(Decrease in
DNA synthesis)

Hemorrhage
Hemolysis
Hypersplenism Def/Disordered metab.
of Folate / vit B12
Recovery from TEC/Aplastic
Ineffective erythropoiesis
crisis in G6PD Def or marrow failure
Fanconi’s
Diamond Blackphan
Severe aplastic anemia
Myelodysplasia
Liver disease
Hypothyroidism
 Elevated MCV

Oval macrocytes Round macrocytes

Hypersegmented PMNs Absence of
+/_ Giant platelets hypersegmented PMNs

Folate/Vit B12 def

Inborn error of folate metabolism

Myelodysplasia
Bone marrow failure
 Folate def
 Consumption of goat’s milk
 Malabsorption
 Increased utilisation (Chronic hemolytic
anemia)
 Genetic diseases of impaired metabolism
 Drugs – Methotrexate, mercaptopurine,
Phenytoin, Trimethoprim – sulpha
 Glossitis
 Evidence of mucosal atrophy
 Vit B12 def
 Extremely rare except in strict vegans
 Malabsorption
 Pernicious anemia
 Inherited disorders of transport or
metabolism
 Paresthesia, Ataxia, Spastic weakness of
legs more than arms
Macrocytic anemia D/D
 In <6 Mo : Diamond Blackfan anemia
 Typical facies : Fanconi’s anemia, DBA
 Liver disease
 Hypothyroidism
 Bone marrow studies
in case myelodysplasia or bone
marrow failure is suspected
 Normocytic anemia
Pancytopenia absent
Pancytopenia

PBS Low retic count High

Disordered erythropoiesis retic count
(Anisopiikilocytosis Anemia of
Nucleated RBCs Acute or
Immatured white cells chronic
Decreased platelets inflamation
Acute viral illness
Aplastic anemia Liver disease
Leukemia Renal insufficiency
Infiltration Endocrinopathy
Myelodysplasia Nutritional anemia
Osteopetrosis Hemorrhage
Storage disorder Hemolysis
Hemolytic anemia
 Family history of anemia,
splenomegaly,jaundice, gallstones
 Ethnic background
 Increase in plasma Hb, decrease in serum
haptoglobin, presence of hemoglobinuria
suggest intravascular hemolysis
 MCHC > 35, RDW > 14, Spherocytosis
suggest hereditory spherocytosis
G6PD Def
 Mediterranean or African descent
 Acute intravascular hemolysis after
infection or oxidant stress
 PBS : Schistocytes and spherocytes
initially, N after enzyme def cells are
hemolysed
Acquired hemolytic anemia
 Coomb’s test + : Immune mediated
 Followingviral illness
 Exposure to drug
 Generalized autoimmune process like Lupus
 Rh & ABO incompatibility in neonate

 Other causes
 Toxins
 Mechanical (abnormal heart valves)
 DIC