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

 Aplastic

Anemia  Pure red cell aplasia  Marrow replacement (Malignancy)  Osteopetrosis  Myelofibrosis
 Chronic

renal disease  Vitamin D deficiency
 Infection

(Tb)

Ineffective red cell production
 Impaired
 Chronic

erythropoietin production

renal disease  Hypothyroidism, Hypopituitarism  Chronic inflammation  Protein malnutrition  Hb mutants (decreased affinity for oxygen)

Ineffective red cell production
 Abnormalities
 Iron

of cytoplasmic maturation

deficiency  Thalassemia syndromes  Sideroblastic anemias  Lead poisoning

Ineffective red cell production
 Abnormalities
 Vit

of nuclear maturation

B12 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  Physical

examination  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
No lymphadenopathy/Hepatosplenomegaly No patechiae/ Echymosis With Patechiae With Patechiae LNpathy HepatoSplenomegaly With Hepato splenomegaly

Nutritional Iron def Megaloblastic Pure red cell aplasia Thal trait Red cell enzyme def Lead poisoning Renal disease

Aplastic anemia Bleeding disorder Coagulation disorder ITP DIC

Thal Hbpathies Liver disorders

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 4

synthesis
hemoglobinopathy

 Inherited

main D/Ds

 Iron

def  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 level

Sensitive indicator of Iron def

 Lead

Microcytic anemia D/D
 Free
N

Erythrocyte Protoporphyrine(FEP)

in Thal  Increased in Iron def and Lead poisoning
 LDH,  ESR
 Increased

Bilirubin
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 reticulocytosis Paucity of Reticulocytes (Decrease in DNA synthesis)

Hemorrhage Hemolysis Hypersplenism Recovery from TEC/Aplastic crisis in G6PD Def

Def/Disordered metab. of Folate / vit B12 Ineffective erythropoiesis or marrow failure Fanconi’s Diamond Blackphan Severe aplastic anemia Myelodysplasia Liver disease Hypothyroidism

Elevated MCV

Oval macrocytes Hypersegmented PMNs +/_ Giant platelets

Round macrocytes Absence of 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 PBS Disordered erythropoiesis (Anisopiikilocytosis Nucleated RBCs Immatured white cells Decreased platelets Pancytopenia absent Low retic count Anemia of Acute or chronic inflamation Acute viral illness Liver disease Renal insufficiency Endocrinopathy Nutritional anemia High retic count

Aplastic anemia Leukemia Infiltration Myelodysplasia Osteopetrosis Storage disorder

Hemorrhage 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

 Following

viral illness  Exposure to drug  Generalized autoimmune process like Lupus  Rh & ABO incompatibility in neonate
 Other

causes
(abnormal heart valves)

 Toxins  Mechanical  DIC

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