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Anemia

Dr.Nadjwa Zamalek Dalimoenthe, SpPK

Anemia
Inability of the blood to supply the
tissue with adequate oxygen for
proper metabolic function.
Determining specific cause of
anemia is important appropriate
management.

Anemia :

Laboratory diagnostic of anemia


decrease level of :
Hemoglobin
Hematocrit
RBC count

Based on Hemoglobin level :


Anemia classified as :
Moderate (Hb 7-10 g/dL)
Severe (Hb < 7 g/dL)

Reference Range Values for


Hemoglobin
Age Group

Hemoglobin (g/dL)

Infants :
Newborns (<1 wk)
6 mo
Children (1-15 yo)

14.0 22
11.0 - 14
11.0 - 15

Adults :
Men
Women

14.0 18
12.0 - 16

Clinical symptoms of anemia :

Pallor
Weakness
Fatigue
Lethargy or malaise
Exercise dyspnea
Palpitation
Pica (consumption of
substance such as ice,
starch, or clay,
frequently found in
IDA)

Syncope (particularly
following exercise)
Dizziness
Headache
Tinnitus or vertigo
Irritability
Difficulty sleeping or
concentrating
Gastrointestinal
symptoms

Causes of anemia

Blood loss (hemorrhage)


Accelerated destruction of RBCs (immune and
nonimmune hemolytic)
Nutritional deficiency (folate or Vitamin B12)
Bonemarrow replacement (e.g., by cancer)
Infection
Toxicity
Hematopoietic stem cell arrest or damage
Hereditary or acquired defect
Unknown

Classification of anemia
Hemoglobin and Hematocrit
Red Blood Cell Indices
Red Blood Cell Indices and other
tests

Classification of anemia by
RBC Indices
Size (MCV)
(fL)

Hgb content
(MCHC) (%)

Possible causes

Normocytic
(80-100)

Normochromic
(32-36)

Bonemarrow failure, hemolytic anemia,


chronic renal disease, leukemia,
metastatic malignancy

Macrocytic
(>100)

Normochromic
(32-36)

Megaloblastic and nonmegaloblastic


macrocytic anemias (e.g.,liver disease,
myelodysplasia)

Microcytic
(<80)

Hypochromic
(<32)

Iron deficiency, sideroblastic anemia,


thalassemia, lead poisoning, chronic
diseases, chronic infection or
inflammation, unstable hemoglobins

Laboratory Tests in the


Diagnosis of Anemia
1.
2.
3.
4.
5.
6.

Hemoglobin
Hematocrit
Red Blood Cell Indices
Peripheral Blood Smear (PBS)
Reticulocyte Count
Bone Marrow Smear & Biopsy

1. Hemoglobin

3 methods for measuring hemoglobin :

Cyanmethemoglobin (*)
Oxyhemoglobin
Measured Iron content

Cyanmethemoglobin method :

Blood is diluted in a solution of Potassium ferricyanide and


potassium cyanide, which oxidizes the hemoglobin to form
methemoglobin.
Subsequently, methemoglobin forms cyanmethemoglobin in
the presence of potassium cyanide.
Because the absorption maximum occurs at a wavelength of
540 nm, the absorbance of solution is read in a
spectrophotometer at 540 nm, and compared with a standard
cyanmethemoglobin solution.

Cyanmethemoglobin
method

Blood

K3Fe(CN)6

methemoglobin

KCN

methemoglobin

cyanmethemoglobin
Read the solutions
absorbance with
spectrophotometer at 540 nm

Advantages of
Cyanmethemoglobin method
1.
2.
3.
4.

Most forms of hemoglobin are


measured
Sample can be directly compared
with a standard
The solutions are stable
Coefficient of variation < 2% at
physiologic ranges

Errors :
1.
2.
3.
4.

Improperly drawing or handling the


specimen
Poorly prepared or stored reagents
Faulty equipment
Operator error

2. Hematocrit
Problems in measurement :
Incorrect centrifuge calibration
Choice of sample site
Incorrect ratio of anticoagulant to
blood owing to improper amount of
blood drawn
Reading error

3. Red Blood Cell Indices


MCV
Microcytic
anemia

50-80 fL

Macrocytic 100-120
anemia
fL

MCH
15-25 pg

MCHC
22-30%

Increased if
N or
decreased spherocytosis
(+)

4. Peripheral Blood Smear

Much information concerning the cause of anemia can be


determined from a PBS.
Coexistent neutropenia, thrombocytopenia, and anemia :

bone marrow failure


Lack of a nutritional substance to provide adequate bone marrow
production

Excess lobulation of PMN (Hypersegmentation) macrocytic


anemia
Basophilic stippling in RBC :

increased bone marrow production and reticulocytosis


Remnants of RNA (lead poisoning, malignancy)

5. Reticulocyte Count

Useful in determining the response and potential


of the bone marrow
Reticulocytes are non-nucleated RBCs that still
contain RNA.
Reticulocytes maybe visualized after incubation
with supravital dyes (New Methylen Blue,
Brilliant Cresyl Blue)
Normal range : 0.5 2.0 % from RBCs

Leukemia

Definition

Leukemia is a malignant disease of


hematopoietic tissue, characterized
by replacement of normal bone
marrow elements with abnormal
(neoplastic) blood cells.

Classification of Leukemia
Acute Myeloid
Acute Lymphoblastic
Chronic Myeloid
Chronic Lymphoid

Classification of Acute
Myeloid Leukemia
Type of Leukemia

Abbrevation

FAB*

Alternate Names

Acute Myeloblastic Leukemia :


-without cytologic maturation
-With minimal maturation
-With maturation

AML

Acute Promyelocytic Leukemia

APL

M3

Hypergranular
promyelocytic

Acute Myelomonocytic Leukemia

AMML

M4

Naegeli-type
leukemia

Acute Monocytic Leukemia

AMoL

M5

Schilling-type
leukemia

Erythroleukemia

AEL

M6

Di Guglielmos
syndrome.
Eryhtremic myelosis

Acute Megakaryoblastic Leukemia

AMegL

M7

M0
M1
M2

Acute Nonlymphoblastic Leukemia


(ANLL)

Classification of Acute
Lymphoblastic Leukemia
Type of Leukemia

Abbrevation

FAB

Alternate Name

Precursor B-cell ALL :


-early-pre-B-cell ALL
-Pre-B-cell ALL

L1,L2
L1,L2

Common ALL
Common ALL

B-cell ALL

L3

Burkitts leukemia

T-cell ALL

L1,L2

Classification of Chronic
Myeloid Leukemia
Type of Leukemia

Abbrevation

Chronic Myelogenous Leukemia

CML

Chronic Eosinophilic Leukemia

CEL

Chronic Basophilic Leukemia

CBL

FAB

Alternate Names
Chronic Granulocytic Leukemia

Classification of Chronic
Lymphocytic Leukemia
Type of leukemia

Abbrevation

Chronic Lymphocytic Leukemia


-B-cell CLL
-T-cell CLL

CLL

Prolymphocytic Leukemia

PLL

Hairy Cell Leukemia

HCL

Sezary syndrome

FAB

Alternate Names

Leukemic reticuloendotheliosis
Mycosis fungoides,
leukemic phase

Etiology and Risk Factors

Host Factors :

Heredity
Congenital Chromosomal Abnormalities
Immunodeficiency
Chronic Marrow Dysfunction

Environmental Factors :

Ionizing Radiation
Chemicals and Drugs
Viruses

Incidence
In USA : 8-10 new cases/100.000
individuals/year.
Increases exponentially with age
Ratio adult : children = 10 : 1
Ratio males : females = 1-2 : 1
ALL more common in children, AML
more common in adults

Comparison of Acute and


Chronic Leukemia
ACUTE

CHRONIC

Age

All ages

Adults

Clinical onset

Sudden

Insidious

Course (untreated)

< 6 mo

2-6 yr

Leukemic cells

Immature

Mature

Anemia

Mild to severe

Mild

Thrombocytopenia

Mild to severe

Mild

White Blood Cell count

Variable

Increased

Organomegaly

Mild

Prominent

Clinical Features of Acute


Leukemia
Pathogenesis

Clinical Manifestation

Bone Marrow Failure


Anemia

Fatigue, malaise, pallor

Thrombocytopenia

Bruising, bleeding

Granulocytopenia

Fever, infections

Organ Infiltration
Marrow expansion

Bone or joint pain

Spleen

Splenomegaly

Liver

Hepatomegaly

Lymph nodes

Lymphadenopathy

Central Nervous system

Neurologic symptoms

Gums,mouth

Gingival hypertrophy, oral lessions

Laboratory Evaluation of
Acute Leukemia
1.
2.
3.
4.
5.

CBC/peripheral blood smear.


Cytochemistry
Immunologic marker studies
Cytogenetics
Molecular genetics

1. CBC/Peripheral Blood
Smear

Anemia :

Platelet : decrease
WBC count :

Mild to severe
Normochrom normocytic

Highly variable : decrease markedly


increase

PBS :

Reveals blast/other immature cells


(incl.normoblast)

2. Cytochemistry

Special stains to identify chemical components of


cells (enzymes, lipids) specific for certain cell
lines
Includes :

Myeloperoxidase
Sudan Black B
Specific Esterase
Nonspecific Esterase
Periodeic Acid Schiff (PAS)

3. Immunologic Marker
Studies
1.
2.
3.

Cell surface markers


Cytoplasmic markers
Terminal deoxynucleotidyl
Transferase (TdT)

Reference Book:
Denise M.Harmening
Clinical Hematology and Fundamentals
of Hemostasis, 4th edition, 2001
Anemia
Leukemia

: pp 74-83
: pp 272-300

Thank You

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