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

Hemoglobin (g/dL)
14.0 22 11.0 - 14 11.0 - 15 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) Normocytic (80-100) Hgb content (MCHC) (%) Normochromic (32-36) Possible causes Bonemarrow failure, hemolytic anemia, chronic renal disease, leukemia, metastatic malignancy Megaloblastic and nonmegaloblastic macrocytic anemias (e.g.,liver disease, myelodysplasia) Iron deficiency, sideroblastic anemia, thalassemia, lead poisoning, chronic diseases, chronic infection or inflammation, unstable hemoglobins

Macrocytic (>100)

Normochromic (32-36)

Microcytic (<80)

Hypochromic (<32)

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
K3Fe(CN)6

Blood

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

MCH
15-25 pg

MCHC
22-30%

Macrocytic 100-120 anemia fL

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
Acute Myeloblastic Leukemia : -without cytologic maturation -With minimal maturation -With maturation Acute Promyelocytic Leukemia Acute Myelomonocytic Leukemia Acute Monocytic Leukemia Erythroleukemia

Abbrevation
AML M0 M1 M2 APL AMML AMoL AEL M3 M4 M5 M6

FAB*

Alternate Names
Acute Nonlymphoblastic Leukemia (ANLL) Hypergranular promyelocytic Naegeli-type leukemia Schilling-type leukemia Di Guglielmos syndrome. Eryhtremic myelosis

Acute Megakaryoblastic Leukemia

AMegL

M7

Classification of Acute Lymphoblastic Leukemia

Type of Leukemia Precursor B-cell ALL : -early-pre-B-cell ALL -Pre-B-cell ALL B-cell ALL T-cell ALL Abbrevation FAB Alternate Name

L1,L2 L1,L2
L3 L1,L2

Common ALL Common ALL

Burkitts leukemia

Classification of Chronic Myeloid Leukemia

Type of Leukemia Chronic Myelogenous Leukemia Chronic Eosinophilic Leukemia Chronic Basophilic Leukemia Abbrevation CML CEL CBL FAB Alternate Names Chronic Granulocytic Leukemia

Classification of Chronic Lymphocytic Leukemia

Type of leukemia Chronic Lymphocytic Leukemia -B-cell CLL -T-cell CLL Abbrevation CLL FAB Alternate Names

Prolymphocytic Leukemia
Hairy Cell Leukemia

PLL
HCL Leukemic reticuloendotheliosis

Sezary syndrome

Mycosis fungoides, leukemic phase

Etiology and Risk Factors

Host Factors :

Heredity Congenital Chromosomal Abnormalities Immunodeficiency Chronic Marrow Dysfunction Ionizing Radiation Chemicals and Drugs Viruses

Environmental Factors :

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 Age Clinical onset Course (untreated) Leukemic cells Anemia Thrombocytopenia White Blood Cell count Organomegaly All ages Sudden < 6 mo Immature Mild to severe Mild to severe Variable Mild Adults Insidious 2-6 yr Mature Mild Mild Increased Prominent CHRONIC

Clinical Features of Acute Leukemia

Pathogenesis Bone Marrow Failure Clinical Manifestation

Anemia
Thrombocytopenia Granulocytopenia Organ Infiltration Marrow expansion Spleen

Fatigue, malaise, pallor

Bruising, bleeding Fever, infections Bone or joint pain Splenomegaly

Liver
Lymph nodes Central Nervous system Gums,mouth

Hepatomegaly
Lymphadenopathy Neurologic symptoms 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 :

Mild to severe Normochrom normocytic

Platelet : decrease WBC count :

Highly variable : decrease markedly increase Reveals blast/other immature cells (incl.normoblast)

PBS :

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