Mitz

ANEMIA
Pedia II

Anemia diminution in the ff:

2SD below the mean
Circulating RBC
Hct
Red cell count
- occurs when erythropoeisis fails to compensate
Non-specific symptoms Anemia
Fatigue
Dyspnea
Exertional dyspnea
Dec. Exercise tolerance

If anemia develops rapidly, symptoms will be more pronounced

If anemia develops very slowly, symptoms may be minimal even
though the anemia may be profound.
Physical examination
Pallor of face, nailbeds, palms
Tachycardia
Flow murmurs
The initial diagnostic approach to the anemic patient includes a
detailed history and physical examination and a minimum of
essential laboratory tests
Historical Factors of Importance in Evaluating Patients with Anemia
Age
Double birthweight
Sex
x-linked disorders
Race
G6PD Asians & Filipinos
thalassemia genes may present with jaundice
Mediterranean
Ethnic
Neonatal
Diet
For hemoglobin production
Fe++, Folic Acid, Vit B12
Drugs
Chloramphenicol production
Cotrimoxazole destruction
Or any w/ sulfa
Infection
Malaria can cause hemolysis
Hepa B, C notorious for acquired aplastic
anemia
IM
Monocytosis & sometimes thrombocytopenia
Inheritance
G6PD
Thalassemia
Diarrhea
Malabsorption
Occult blood loss
Physical Findings as Clues to the Etiology of Anemia
Skin
Hyperpigmentation,
Fanconis aplastic anemia
petechiae
AIHA w/ thrombocytopenia
purpura
Hemolytic anemia
jaundice
Hepatitis
Facies
Frontal
bowing?, Congenital hemolytic
anemia
prominence of molar
& maxillary bone
Thalassemia major
Severe IDA
Mouth
Glossitis
Vit B12 def.
angular stomatitis
Iron deficiency
Hands
Triphalangeal
Red cell aplasia
thumbs
Fanconis aplastic anemia
hypoplasia of thenar IDA
eminence
spoon nails
Spleen Enlargement
Congenital hemolytic
anemia
Leukemia
Lymphoma
Acute infection
Portal hypertension
Initial Laboratory Tests
Hgb, Hct
Red cell indices
Platelet count
White cell count & differential
Reticulocyte count
Examination of Peripheral smear

Two Main Classifications of Anemia

I. Morphologic classification based on red cell size, MCV
Normochromic, normocytic
Hypochromic, microcytic
Macrocytic
II. Physiologic Classification
Anemias due to red cell underproduction
Anemias due to increase red cell destruction
Anemia of blood loss
Sequestration in spleen
Red Cell Values for Different Age
Age
Hgb g/dL
Hct%
Birth
13.5 20
42 60
3-6
9.5 13.5
28 42
months
0.5 2 yrs
10.5 13.5
33 39
6 12 yrs
11.5 15.5
35 45
12 18 yrs
M
13 16
37 49
F
12 16
36 46
18 49 yrs
M
13.5 17.5
41 53
F
12 16
36 46

MCV
98 118

Retic
1.8 4.6

74 108

0.4 1.0

70 86
77 95

0.2 1.8
0.2 1.8

78 98
78 102

0.2 1.8

80 100
80 100

0.2 1.8

RED CELL INDICES

Hematocrit x 10
RBC/ul
- directly derived from automated blood counter
- most reliable
- Average size of individual RBC

MCV (fl) =

Hemoglobin x 10
RBC/ul
- Expression of absolute units of hemoglobin contained in
rbcs

MCH (pg) =

Hemoglobin x 100
Hematocrit
- Express mean concentration of Hb

MCHC (g/dl) =

Anemia
MCV
Low
Iron deficiency
Thalassemia
Lead Poisoning
Chronic Disease

Normal

High
Folate Deficiency
Vit B12 deficiency
Aplastic anemia
Preleukemia
Immune Hemolysis
Liver Disease

Reticulocyte count
High

Low

High bilirubin

BM defect

Hemolytic Anemia
Maturation Time in Days
Hematocrit
Marrow normoblasts
%
& reticulocytes
45
3.5
35
3.0
25
2.5
15
1.5

Blood reticulocytes
1.0
1.5
2.0
2.5

Number of days for maturation of reticulocytes of the marrow &

blood. The duration of maturation in blood reticulocytes is taken as
is.
Corrected Reticulocyte count
Observed Hct
Retic count (%) X
Normal Hct for Age
Reticulocyte production index
Corrected Retic count (%) X

N: 2
1
Maturation time

*maturation time depends on Hct level (see Nelson)

The examination of the blood smear is the single most useful

procedure in the initial evaluation of patients with anemia.

Mitz
Hemolytic Anemia
Coombs Test
Negative
Corpuscular
Extracorpuscular
Hemoglobinopathies
Enzymopathies
Membrane defects
Morphology
Autohemolysis
Osmotic Fragility

Positive
Extracorpuscular
AUTOIMMUNE
HEMOLYTIC ANEMIA
Primary
Secondary (CT
disease, drugs,
infection)
Isoimmune
Hemolytic disease
Rh,
ABO,
mismatched
transfusion

HEMATOPOEISIS
Competent microenvironment BM failure/infiltration
Growth Factors EPO
Nutrients
Vitamin B12
Folic acid essential in the formation of thymidine
triphosphate for DNA synthesis
Porphyrin, globin, iron
ANEMIA OF INADEQUATE PRODUCTION
PURE RED CELL APLASIA
- Congenital (DBA)
 Intrinsic hematopoetic stem cell defect where erythroid
progenitors & precursors are highly sensitive to death by
apoptosis
 Dominant inheritance in majority of cases
- Acquired (TEC)
 Usually occurs after a non specific viral illness producing
serum (IgG) and cellular (mononuclears) inhibitors of
erythropoesis.
Difference between DBA & TEC
Features
DBA
Frequency
Rare (5-10/106 live
births)
Age at dx
90%, by 1yr
25%, at birth or w/n
2 mos
Etiology
Genetic
Familial
Antecedent Hx
Congenital
abnormality
Course

Transfer
dependence
MCV (for age)
Hb F (for age)
I Ag
Erythrocyte
adenosine
deaminase
Treatment

Yes (in 10-20% of

cases)
None
Present 50% cases
(heart,
kidneys,
musculoskeletal)
Prolonged,
20%
actuarial probability
of remission
Transfer or steroid
dependent
Macrocytic
Elevated chronic
Elevated
Elevated (dec 85%
of cases)
PRBC transfusion
Prednisone 2mkd &
taper
to
lowest
effective dose
Stem
cell
transplantation

TEC
Common
6 mo-4 yrs
Occas. older
Acquired
(viral, idiopathic)
No
Viral illness
Absent

Spontaneous
recovery in weeks to
months
Not dependent
Normocytic
Normal
Usually normal
Not elevated

PRBC transfusion, if
required

APLASTIC ANEMIA
- Congenital (Fanconi anemia)
 Hypersensitivity to chromosomal breakage
 Autosomal recessive, generally associated with multiply
congenital abnormalities
- Acquired
 Results from immunologically mediated, tissue-specific,
organ-destructive mechanism
 IFN messenger RNA and number of activated
cytotoxic lymphocytes

Difference between Fanconi Anemia & TAR

Features
Fanconi Anemia
Age of onset of
Median 7 yrs
hema sxs
Low birth weight
-10%
Stature
Short
Skel deform
66%
Absent rad?
0
LE deform
-40%
Anomalous
77%
pigmentation of skin
cafe au lait spots
Hemangiomas
0
Mental retardation
17%
Peripheral blood
Pancytopenia
Macrocytosis
BMA
Aplastic
Marrow
CFU-GM,
CPU-E
HbF
Chromosomal
breaks in leukocytes
Malignancy
Sex ratio (M/F)
Inheritance pattern
Associated
leukemia
Prognosis

Aquired AA
Infancy to adulthood
N/A
Normal
N/A
N/A
10%
7%
Dec. Platelet,
eosinophilia,
leukemoid reaction,
anemia
Absent
megakaryocyte
Normal myeloid &
erythroid precursors

Decreased

Normal

Increased

Normal

Present
Common
1:1
Autosomal
recessive
Yes
Poor

None
Rare N/A
1:1
Autosomal
recessive
Rare
Preleukemic stage
80% survival rate

Aquired Aplastic Anemia

- BM failure results from immunologically mediated, tissuespecific, organ-destructive mechanism
- IFN messenger RNA, undetectable in most patients with AA
- number of activated cytotoxic lymphocytes are present in the
blood and BM
- Tx w/ ATG & Cyclosporine cytotoxic cells
- Immunosuppressive tx improves pancytopenia
Causes
- Idiopathic (70%) or more of cases, 30% identifiable
- Secondary
Drugs.
Predictable, dose dependent, unpredictable, normal doses
rapidly reversible
6MP
antibiotics chloramphenicol,
MTX
sulfonamides
cyclophosphamide
anticonvulsants mephentoin,
hydantoin
busulfan
antirheumatics
chloramphenicol
phenybutazone, gold
antidiabetics tolbutamide,
chlorpropamide
antimalarial - quinacrine
Chemicals: insecticides
Toxins (benzene, carbon tetrachloride, glue)
Irradiation high dose (AA/radiation induced malignancy)
Infections: viral heap (a, b, c, etc), HIV, infectious mono,
measles, mumps, rubella, chronic parvovirus
Immunoopathologic dse
Malnutrition
Pregnancy
Clinical Findings
- Anemia pallor, easy fatigability, weakness
- Thrombocytopenia bleeding (fever)
- Leukopenia infections, oral ulcers
- Hepatosplenomegaly & lymphadenopathy do not occur
NO
ORGAN ENLARGEMENT IN AA
- Hyperplastic gingivitis is also a symptom of AA
(bec of some infection
AML M4, M5)
Lab findings
- pancytopenia (normochromic or macrocytic)
- reticulocytopenia
- fetal hgb maybe elevated
- BM replaced by fatty tx
- Chromosomal blockage assay: normal (to r/o FA)
Severe AA
- BM cellularity <25%
- And at least 2 of the ff
o Anc <500/mm3
o Pc < 20,000/mm3
o Retic count < 40,000/mm3

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Treatment
- supportive care
- for severe AA
o BM transplantation
o Immunosuppressive treatment
ANEMIA OF CHRONIC DISEASE AND RENAL DSE
- associated with infections, inflammation or tissue breakdown
(pyogenic inflammation)
 release of IL1 and TNF leading to production of IFN B
and IFN gamma
- s/sx those of underlying dse
- normocytic, normochromic (unless theres iron deficiency)
- lab: NNRBC, retic count normal or low
 leukocytosis common
 serum ferritin maybe elevated
does not mean you are replete with iron
 diagnostic feature: serum iron low, TIBC low to normal
- Anemia of Renal Dse
 Dec production of EPO
 Normocytic normochromic
 Microcytic hypochromic if there is concomitant IDA in Px
undergoing dialysis

MEGALOBLASTIC ANEMIAS
- folate green veggies, fruits, animal organs
- clinical manifestation: sign and symptoms of anemia
- Lab
 Macrocytic RBC
 Low retic count
 Nucleated RBC in PBS
 Hypersegmented neutrophils
 Low serum and RBC folate
 BMA erythroid hyperplasia
Vit B12 from animal sources
- older children sufficient stores 3-5 years
- infants born to mothers with low B12 4-5 months
- clinical manifestations
 signs and symptoms of anemia
 neurologic symptoms
- - laboratory
 similar to folic acid deficiency
 inc methylmalonic acid in the urine
- - Treatment
 Vit B12, IM

IRON DEFICIENCY ANEMIA

- 60% of iron is in the circulating hemoglobin
- 15 to 20% is stored in reticuloendothelial system
 if needed can be delivered into plasma -> bone marrow
- use only 1-2mg of iron per day
- same amt of iron is absorbed from the GIT
- increased blood loss / inc demand for iron -> IDA
- most common cause of anemia
- peak prev occurs in late infancy and early childhood
 period of rapid growth
 low levels of dietary iron
 complicating effect of cows milk (exudative enteropathy)
- second peak: adolescence
- causes:
 deficient intake
 increased demand
 blood loss
 impaired absorption

ANEMIA OF INCREASED DESTRUCTION

Areas of RBC important in normal function and survival
- membrane
- hemoglobin structure
Approach to Dx :
Clinical features suggesting hemolysis
Laboratory demonstration of hemolytic process
Determination of precise cause

Tissue effects of IDA

- GIT anorexia, pica, atrophic glossitis, leaky gut syndrome
(exudative enteropathy)
- CNS irritability, conduct disorder, dec cognitive function
- CVS inc HR and CO, cardiac hypertrophy, inc plasma
volume
- Immunologic inc propensity to infection







DX
- low Hb
- low RBC indices, high RDW
- retic count usually normal; if associated with bleeding, retic
count of 3-4% may occur
- platelet low in severe IDA, high if with GI bleeding
- free erythrocyte protoporphyrin high
- low serum ferritin (<12ng/ml)
- serum iron low, serum transferrin high
- therapeutic trial most reliable criterion
Stages
Iron depletion
- Storage iron is absent or decreased
- Normal serum Fe concentration & Hgb levels
Iron deficiency without anemia
- Decreased or absent storage iron
- Low serum iron concentration
- Low transferrin
- No frank anemia
Iron deficiency anemia
- Low Hgb/Hct values
Clinical consequences of Iron deposition
1. cardiac abnormalities
2. hepatic abnormalities
3. endocrine abnormalities
a. growth retardation
b. failure of sexual maturation
c. subclinical hypothryoidism
d. diabetes mellitus
e. hypoparathyroidism

Clinical Features
1. Ethnic factors Thalassemia Mediterreanean ancestry,
Asians
2. Age factors infants with ABO/Rh incompatibility setting
3. Hx of anemia, jaundice, gallstones in the family
4. persistent and recurrent anemia w/ reticulocytosis
5. anemia unresponsive to hematinics
6. splenomegaly
7. hemoglobinuria
Membrane defects - HS
Enzyme defects - G6PD deficiency
Hemoglobinopathies HbS, Thalassemia
AIHA
Fragmentation hemolysis px w/ heart valves, DIC

Membrane Composition and Structure

RBC Membrane Lipids
- bilayer of phospholipids interspersed with molecules of
unesterified cholesterol and glycolipids
- cholesterol composes 25% of RBC membrane lipid in 1:1
molar ratio with glycolipids
- accumulation of cholesterol target cells, acanthocytes,
chronic HA
Normal adult RBC contain the ff types of hemoglobin
- Hemoglobin A (alpha2, beta2) 95-97%
- Hemoglobin A2 (alpha2, delta2) 2-3.4%
- Hemoglobin F (alpha2, gamma2) 1-2%
Disorders of Hemoglobin Production
- Thalassemias decreased production of alpha or beta globin
- Hemoglobinopathies abnormal polypeptide chains are
produced
Hb S alpha chains are normal but in Beta chain, 1
glutamic residue was replaced by valine reside
Polymerizes at low O2 tension
RBC Metabolic Pathways
- necessary for the production of adequate ATP levels to
maintain
 Hb function
 Membrane integrity and deformability
 RBC volume
 Adequate amounts of reduced pyridine nucleotides
- Embden Mayerhoff Pathway
- Methemoglobin reductase pathway maintain iron in ferrous
state
- Phosphogluconate pathway

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THALASSEMIA
nRBC & polychromasia
ineffective erythropoeisis
hemolysis
thalassemias syndromes
Syndrome
Silent carrier

Thal. Trait

HbH disease

Hydrops fetalis

Clinical/Lab features
No anemia
N RBC
1-2% Hgb Barts @ birth
Mild anemia
Hypo micro RBC
10% Hgb Barts @ birth
Mod anemia
Hypo micro RBC
Inclusion bodies may be
demonstrated
5-30% HbH (?)
>
Golf ball cells ppt!
Incompatible to life Death
in utero caused by severe
anemia
Mainly Hgb Barts

-thalassemia
chains affected
1

Clinical Classification of -thalassemias

Silent carrier
Hematologically normal
Thal. Trait
Mild anemia w/ microcytosis & hypochromia
Severe anemia
Growth retardation
Severe beta thal.
Hepatosplenomegaly
(Cooleys anemia)
BM expansion
Bone deformities

G6PD DEFICIENCY
Sex-linked recessive inheritance (x chromosome)
Fully expressed in hemizygous male and homozygous female
3% of worlds population affected
Clinical Manifestations
1. Acute Hemolityc Anemia
- Within 6-24 hours after exposure to exudative challenge
- There may be passage of dark, brown or black urine
- With 24-28 hrs elevationof temperature, nausea,
abnominal pain, diarrhea
2. Neonatal jaundice
Diagnosis
Screening tests
- dye decolorization test
G6PD Enzyme Assay
Treatment
Prevention from exposure to agents that cause hemolysis
Blood transfusions
HEREDITARY SPHEROCYTOSIS
Autosomal dominant
Characterized osmotically fragile
Spherical red cells that are trapped by the spleen
Defect in spectrin
Clinical Features:
Anemia most frequent presenting complaint
Jaundice
Splenomegaly
(+) family history
Laboratory Features:
Peripheral smear microspherocytes
Reticulocyte count elevated
Osmotic Fragility test
Treatment
Splenectomy
Diseases associated with AIHA in childhood
Infections
Viral infections, especially respiratory infections
Infectious mononucleosis and cytomegalovirus
Mycoplasma, especially pneumonia
HIV infection
Disorders associated with antibody production
SLE
Thyroid disorders
Neonatal Lupus syndrome
Ulcerative colitis
Rheumatoid arthritis
Chronic active hepatitis

AIHA
Immunodeficiency syndromes
X-linked agammaglobulinemia
Dysgammaglobulinemia
Common variable hypogammaglobulinemia
IgA deficiency
Wiskott-Aldrich syndrome
HIV infection
Malignancies
Non-hodgkins lymphoma
Carcinoma
Hodgkins disease
Thymoma
Acute lymphocytic leukemia
Ovarian cysts & tumor
Clinical Features:
Pallor, jaundice, dark urine, abdominal pain, fever
Splenomegaly, hepatomegaly
Laboratory Features:
Anemia
Reticulocytosis
(+) Coombs test
PBS- spherocytes, polychromasia, nucleated RBC
May be associated with thrombocytopenia, leukopenia
Treatment:
1. Corticosteroid
2. Transfusion
3. Plasmapheresis
4. IVIG
5. Splenectomy
6. Immunosuppressives
HEMOLYTIC ANEMIA
Evidence of destruction
1. Anemia
2. Jaundice
3. Bilirubin (B1)
4. Hemoglobinuria
5. Urinary urobilinogen
6. Hepatosplenomegaly

Regeneration
1. Reticulocytosis
2. Normoblastemia
3. Erythroid hyperplasia

Laboratory anomalies in Hemolytic Anemia

Test
Abnormality
PBS
Spherocytes
Fragments
Blister cells
Agglutination
Macrocytes
Polychromatophilia
Sickle cells
Reticulocyte count
Usually elevated
Serum haptoglobin
Low
Serum LDH
Elevated
Red cell survival
Shortened
Bilirubin
Elevated indirect fraction
Laboratory Procedures:
1. Stool guiac test
2. Serum ferritin, iron, TIBC, transferrin saturation, FEP
3. Coombs test (direct & indirect)
4. Hemoglobin electrophoresis
5. Osmotic Fragility test
6. Hams test / Sucrose lysis test
7. RBC enzyme assay / G6PD screening test
Treatment:
Depends on the cause
Nutrient replacement
Ferrous sulfate
Folic acid/Vit B12
rhuEPO
 50-300 u/kg 3x a week
 indication: end stage renal dse
 other uses: cancer related anemia, post chemotherapy
or BMT, anemia in aplastic anemia, MDS and AIDS
Steroids
Blood transfusion

Transcribed by: Ann Mitzel Gawaran Mata-(?)