4. Anemia & Leukemia

7/27/2019 4. Anemia & Leukemia

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AnemiaDr.Nadjwa Zamalek Dalimoenthe, SpPK


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Anemia

Inability of the blood to supply thetissue with adequate oxygen for

proper metabolic function. Determining specific cause of

anemia is important appropriate

management.


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Anemia :

Laboratory diagnostic of anemia decrease level of :

Hemoglobin Hematocrit

RBC count


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Based on Hemoglobin level :

Anemia classified as :

Moderate (Hb 7-10 g/dL)

Severe (Hb < 7 g/dL)


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Reference Range Values forHemoglobin

Age Group Hemoglobin (g/dL)

Infants :

Newborns (


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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 inIDA)

Syncope (particularlyfollowing exercise)

Dizziness

Headache

Tinnitus or vertigo

Irritability

Difficulty sleeping orconcentrating

Gastrointestinalsymptoms


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Causes of anemia

Blood loss (hemorrhage)

Accelerated destruction of RBCs (immune andnonimmune 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


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Classification of anemia

Hemoglobin and Hematocrit

Red Blood Cell Indices

Red Blood Cell Indices and othertests


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Classification of anemia byRBC 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 nonmegaloblasticmacrocytic anemias (e.g.,liver disease,myelodysplasia)

Microcytic(


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Laboratory Tests in theDiagnosis of Anemia

1. Hemoglobin

2. Hematocrit

3. Red Blood Cell Indices

4. Peripheral Blood Smear (PBS)

5. Reticulocyte Count

6. Bone Marrow Smear & Biopsy


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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 formmethemoglobin.

Subsequently, methemoglobin forms cyanmethemoglobin inthe presence of potassium cyanide.

Because the absorption maximum occurs at a wavelength of540 nm, the absorbance of solution is read in aspectrophotometer at 540 nm, and compared with a standardcyanmethemoglobin solution.


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Blood methemoglobinK3Fe(CN)6

methemoglobin cyanmethemoglobin

KCN

Read the solutionsabsorbance with

spectrophotometer at 540 nm

Cyanmethemoglobinmethod


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Advantages ofCyanmethemoglobin method

1. Most forms of hemoglobin aremeasured

2. Sample can be directly comparedwith a standard

3. The solutions are stable

4. Coefficient of variation < 2% atphysiologic ranges


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Errors :

1. Improperly drawing or handling thespecimen

2. Poorly prepared or stored reagents3. Faulty equipment

4. Operator error


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2. Hematocrit

Problems in measurement :

Incorrect centrifuge calibration

Choice of sample site

Incorrect ratio of anticoagulant toblood owing to improper amount of

blood drawn

Reading error


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3. Red Blood Cell Indices

MCV MCH MCHC

Microcytic

anemia

50-80 fL 15-25 pg 22-30%

Macrocytic

anemia

100-120

fL

N or

decreased

Increased ifspherocytosis

(+)


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4. Peripheral Blood Smear

Much information concerning the cause of anemia can bedetermined 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) macrocyticanemia

Basophilic stippling in RBC : increased bone marrow production and reticulocytosis

Remnants of RNA (lead poisoning, malignancy)


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5. Reticulocyte Count

Useful in determining the response and potentialof the bone marrow

Reticulocytes are non-nucleated RBCs that still

contain RNA.

Reticulocytes maybe visualized after incubationwith supravital dyes (New Methylen Blue,Brilliant Cresyl Blue)

Normal range : 0.5 2.0 % from RBCs


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Leukemia


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Definition

Leukemia is a malignant disease ofhematopoietic tissue, characterized

by replacement of normal bonemarrow elements with abnormal(neoplastic) blood cells.


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Classification of Leukemia

Acute Myeloid

Acute Lymphoblastic

Chronic Myeloid

Chronic Lymphoid


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Classification of AcuteMyeloid Leukemia

Type of Leukemia Abbrevation FAB* Alternate Names

Acute Myeloblastic Leukemia :

-without cytologic maturation

-With minimal maturation-With maturation

AML

M0

M1M2

Acute Nonlympho-blastic Leukemia(ANLL)

Acute Promyelocytic Leukemia APL M3 Hypergranularpromyelocytic

Acute Myelomonocytic Leukemia AMML M4 Naegeli-typeleukemia

Acute Monocytic Leukemia AMoL M5 Schilling-typeleukemia

Erythroleukemia AEL M6 Di Guglielmossyndrome. Eryhtremicmyelosis

Acute Megakaryoblastic Leukemia AMegL M7


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Classification of AcuteLymphoblastic 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


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Classification of ChronicMyeloid Leukemia

Type of Leukemia Abbrevation FAB Alternate Names

Chronic Myelogenous Leukemia CML Chronic Granulo-cytic Leukemia

Chronic Eosinophilic Leukemia CEL

Chronic Basophilic Leukemia CBL


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Classification of ChronicLymphocytic Leukemia

Type of leukemia Abbrevation FAB Alternate Names

Chronic Lymphocytic Leukemia

-B-cell CLL

-T-cell CLL

CLL

Prolymphocytic Leukemia PLL

Hairy Cell Leukemia HCL Leukemic reticulo-endotheliosis

Sezary syndrome Mycosis fungoides,leukemic phase


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Etiology and Risk Factors

Host Factors :

Heredity

Congenital Chromosomal Abnormalities

Immunodeficiency

Chronic Marrow Dysfunction

Environmental Factors :

Ionizing Radiation Chemicals and Drugs

Viruses


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Incidence

In USA : 8-10 new cases/100.000individuals/year.

Increases exponentially with age Ratio adult : children = 10 : 1

Ratio males : females = 1-2 : 1

ALL more common in children, AMLmore common in adults


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Comparison of Acute andChronic 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


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Clinical Features of AcuteLeukemia

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


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Laboratory Evaluation ofAcute Leukemia

1. CBC/peripheral blood smear.

2. Cytochemistry

3. Immunologic marker studies

4. Cytogenetics

5. Molecular genetics


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1. CBC/Peripheral BloodSmear

Anemia : Mild to severe

Normochrom normocytic

Platelet : decrease

WBC count : Highly variable : decrease markedly

increase

PBS : Reveals blast/other immature cells

(incl.normoblast)


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2. Cytochemistry

Special stains to identify chemical components ofcells (enzymes, lipids) specific for certain celllines

Includes : Myeloperoxidase

Sudan Black B

Specific Esterase

Nonspecific Esterase Periodeic Acid Schiff (PAS)


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3. Immunologic MarkerStudies

1. Cell surface markers

2. Cytoplasmic markers

3. Terminal deoxynucleotidylTransferase (TdT)


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Reference Book:

Denise M.Harmening

Clinical Hematology and Fundamentals

of Hemostasis, 4th edition, 2001

Anemia : pp 74-83

Leukemia : pp 272-300


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