Introduction to Hematology and Anemia
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Transcript of Introduction to Hematology and Anemia
Introduction to Hematology and Anemia
Download more documents and slide shows on The Medical Post [ www.themedicalpost.net ]
Dr. Kalpana MallaMD Pediatrics
Manipal Teaching Hospital
Blood
• Blood volume is about 8% of body weight• 45 % is formed elements• 55% plasma
PLASMA
90 % Water10 % Solutes - Plasma proteins –
Albumins(58 %) - maintain osmotic (oncotic) pressure
Globulins (38 %) - antibodies synthesized by plasma cells
Clotting factors – fibrinogen – 4 %
FORMED ELEMENTS
• Three types:Erythrocytes – red blood cellsLeukocytes – white blood cellsThrombocytes – platelets – cell fragments
Development of hemopoietic system:3 anatomic stages:
Mesoblastic: in extraembryyonic structures - yolk sac (10- 14 days of gestation till 10-12 wks)
Hepatic: liver 6-8wks gestation - 20-24wks-primary site
of blood cell production (continues till remainder of gestation)
Myeloid: bone marrow (10-12 weeks)
Exception: lymphocytes –bone marrow+ other organs
Developmental changes:
• 2nd to 3rd trimester: circulating erythrocytes and granulocytes increase
• 2nd trimester - Haematocrit levels rise 30-40 % & at term rise is 50-63 % • Platelet concentration remains constant from 18th
wks till term • Life-span of RBCs ~60- 90 days in newborns vs 120
days
• Fetal bone marrow space develops - 8th wk of gestation • Neutrophils first observed ~ 5 wks of gestation • 14th wk to term: most common cell found in bone
marrow is neutrophil • Red marrow:• Newborns- in all cavities of bones• Older children & adults - in upper shaft of femur,
humerus, pelvis, spine, skull and bones of thorax• Erythropoiesis: - In-utero controlled by erythroid growth factors
produced by monocyte-macrophages of fetal liver - After birth controlled by erythropoietin from kidneys
The Red Cell
• Average life span = 120 days (60-90 days NB)• Cleared by RES (spleen, liver primarily)• Homeostasis daily loss = daily production• Otherwise anemia
Hemoglobin:
• Is complex protein - Made up of heme which contains an atom of iron and 4 polypeptide globin chains – reversible transport of Oxygen without expenditure of metabolic energy– Oxygen binds to iron in heme (also CO)– 23 % of CO2 is bound to globin portion
• If there is a problem with any part of the molecule it may not be functional
Types of Hb:
• Embryonic Hb: Gower-1: ζ2 ε2
Gower-2: α2 ε2
Portland: ζ2 2ץ
• Fetal Hb: Hb F: α2 2ץ
• Adult Hb:
Hb A : α2 β2
Hb A1: α2 δ2
Developmental changes in Hb:
• 4-8 wks gestation: Gower Hb predominates; disappears by 3rd month
• > 8th wk of gestation- Hb F predominant Hb• ~ 24 wks gestation 90 % of total Hb• At birth declines to 70 %• 6-12 months postnatal life < 2 %
Developmental changes in Hb:
• 16-20 wks gestation- some Hb A detectable• 24th wk gestation: 5-10 % , At term ~ 30 %Hb A
present• Hb A2 - < 1 % - At birth
- 2-3.4 % At 12 months (normal level)• Throughout life ratio of Hb A: Hb A2 is ~ 30:1
Hgb Norms• Normal values vary by age and gender
– High at Birth 20g/dl since HbF has high affinity for oxygen , by 3 months HbA replaces HbF
– Falls to lower-than-adult values by 3-6 months – Rises gradually to adult value by the early teenage
years– On average, Adult male Hb 2g/dl > female
counterpart due to effect of androgen .
Hgb and MCV VariabilityAge Hgb mean MCV mean
birth 16.5 1082 wk 16.5 1052 mo 11.5 96
6mo-2yr 12.5 772-6 yr 12.7 80
10-12 yr 13.5 8512-17 14 85Adult 14-16 90
Contemporary Pediatrics, Vol 18, No. 9
GRANULOCYTES
• Neutrophils – phagocytes• Eosinophils – red granules, associated with
allergic response and parasitic worms• Basophils – deep blue granules - Release heparin
and histamine
Neutrophil
Eosinophil
Basophil
AGRANULOCYTES
• Granules too small to be visible• Monocytes – become macrophages• Lymphocytes – B cells and T cells = immune
functions
Monocyte
Lymphocyte
Lab Investigation
• Table: Laboratory Tests in Anemia Diagnosis• i. Complete blood count (CBC)• A. Red blood cell count• 1. Hemoglobin• 2. Hematocrit• B. Red blood cell indices• 1. Mean cell volume (MCV)• 2. Mean cell hemoglobin (MCH)• 3. Mean cell hemoglobin concentration (MCHC]• 4. Red cell distribution width (RDW)C.
RBC indices
• Part of the (CBC) - • Mean cell volume(MCV) – Quantifies average red blood
cell size • Mean cell hemoglobin (MCH) –Hb amount per red
blood cell• Mean cell hemoglobin concentration (MCHC) - The
amount of hemoglobin relative to the size of the cell (hemoglobin concentration) per red blood cell
Contd -Red Blood Cell Indices Index Normal Value• MCV = 90 ± 8 hematocrit /red cell count (80 – 100) femtoliter • (MCH) = 30 ± 3 pg
Hb /red cell count (27 - 31)picograms/cell
• (MCHC)= 33 ± 2 Hb/hematocrit or MCH/MCV (32 – 36) gm/dl
Anemias - based on cell size (MCV) and amount of Hgb (MCH)
• MCV < lower limit of normal: microcytic anemia
• MCV normal range: normocytic anemia• MCV > upper limit of normal: macrocytic
anemia• MCH < lower limit of normal: hypochromic
anemia• MCH within normal range: normochromic
anemia• MCH > upper limit of normal: hyperchromic
anemia
Mentzer index
• Calculated number to help differentiate between iron deficiency vs. thalassemia if having microcytic anemia
• MCV/RBC• >13 iron deficiency• <13 thal trait
Red Cell Volume Distribution Width (RDW)• Reflects the variability in cell size
• Aids in further differentiating between specific etiologies of microcytic, normocytic, and macrocytic
• RDW = (Standard deviation of MCV ÷ mean MCV) ×
100
Contd
• C. White blood cell count• 1. Cell differential• 2. Nuclear segmentation of neutrophils• D. Platelet count
Blood smear
• Assess the size, color, and shape of red cells– Look for abnormalities – macrocyte, leptocyte, target cell, Tear drop,
Elliptocytosis,burr cell,acanthocyte, Schistocytes,Spherocytosis,Sickle cells,Poikilocytes– Anisocytosis, Polychromasia
MACROCYTE
Larger than normal >8.5 µm diameter
LEPTOCYTE
Hypochromic cell with a normal diameter and decreased MCV
Thalassemia.
TARGET CELL
Hypochromic with central "target" of hemoglobin. Liver disease, thalassemia, hemoglobin D, postsplenectomy
TEAR DROP CELL
Drop-shaped erythrocyte, often microcytic. Myelofibrosis and infiltration of marrow with tumor. Thalassemia
ELLIPTOCYTE
Oval to cigar shaped. Hereditary elliptocytosis, certain anemias (particularly vitamin B-12 and folate deficiency)
ECHINOCYTE (BURR CELL)
Evenly distributed spicules on surface of RBCs, usually 10-30. Uremia, peptic ulcer, gastric carcinoma, pyruvic kinase deficiency
.
ACANTHOCYTE
Five to 10 spicules of various lengths and at irregular interval on surface of RBCs.
STOMATOCYTE
• Slitlike area of central pallor in erythrocyte. Liver disease, acute alcoholism, malignancies, hereditary stomatocytosis, and artifact
SCHISTOCYTE
Fragmented helmet- or triangular-shaped RBCs. Microangiopathic anemia, artificial heart valves, uremia, malignant hypertension
Microcytic and Hypochromic
Smaller than normal ( <7 µm diameter
Less hemoglobin in cell. Enlarged area of central pallor.
Sickle cellElongated cell with pointed ends.
Hemoglobin S and certain types of hemoglobin C
Spherocyte Loss of central pallor, stains more densely, often microcytic. Hereditary spherocytosis and
certain acquired hemolytic anemias.poikilocytosis &
anisocytosisvariation in shape and variation in size
Contd
• II. Reticulocyte count• III. Iron supply studies• A. Serum iron• B. Total iron-binding capacity• C. Serum ferritin, marrow iron stain
Contd
• IV. Marrow examination• A. Aspirate• 1. E/G ratio• 2. Cell morphology• 3. Iron stain• B. Biopsy• 1. Cellularity• 2. Morphology E/G ratio, ratio of erythroid to
granulocytic precursors.
Reticulocyte Count
• Reticulocyte production index • RPI= Retic ct x Hb(obsv)/ Hb(normal)
x0.5• Indicates whether the BM is
appropriately responding to anemia• RPI >3 : inc prod = blood
loss/hemolysis• RPI <2 : dec prod / ineffective prod
CLASSIFICATION
INADEQUATE RESPONSE (RPI <2)• Hypochromic, microcytic• Normocytic normochromic• Macrocytic
ADEQUATE RESPONSE (RPI >3)• Hemolytic anemia• Blood loss
ANEMIA
What is Anemia?
• Anemia is defined as a reduction of the red blood cell (RBC) volume or hemoglobin concentration below reference level for the age and sex of the individual
• Hb < - 2SD or 95th centile for age and sex
Anemia Basics
All anemias are either due to….
1. Ineffective RBC productionor
2. Accelerated destruction of the RBC
• By RBC morphology and By Etiological factors responsible for anemia
Classification
Microcytic hypochromic anemia
1. Iron deficiency anemia – nutritional, posthemohragic2. Ineffective Erythropoiesis - Abnormal hemoglobinopathies, Thalassemia
syndrome, - Lead poisoning, Cu deficiency,
- Pyridoxine responsive -chronic ds - infection, inflammations , renal ds
MICROCYTIC
TAILS P: • T - Thalassemia
A - Anemia of chronic disease • I - Iron deficiency anemia • L - Lead toxicity associated anemia • S - Sideroblastic anemia • P – Pyridoxine deficiency
• Megaloblastic Erythropoiesis a) Nutritional - Folate deficiency, B12 deficiencyb) Toxic – Treatment with antifolate compound – methotrexate,, and drugs that inhibit DNA
replication – zidovudine, phenytoinc) Congenital disorders of DNA synthesis like Orotic aciduria etc. d) Malabsorption - liver ds - normal newborns, reticulocytosis
Macrocytic anemia
Macrocytic anemia• Non - Megaloblastic Erythropoiesisa) Chronic hemolytic anemia b) Liver dsc) Hypothyroidismd) Diamond blackfan syndrome
1. Impaired cell production (low reticulocyte count) - aplastic anemia - pure red cell aplasia - physiological anemia of infancy - infections - Systemic diseases like endocrinal, renal and hepatic diseases - bone marrow replacement – leukemia, tumors, starage ds, myelofibrosis, osteopetrosis2 Hemolytic anemia ( reticulocyte count high)
Normocytic, Normochromic anemia
DIMORPHIC ANEMIA
• When two causes of anemia act simultaneously, e.g : macrocytic hypochromic due to hookworm infestation leading to deficiency of both iron and vitamin B12 or folic acid
• following a blood transfusion
ETIOLOGICAL CLASSIFICATION OF ANEMIA • Blood loss Acute
Chronic
• Decreased iron assimilation - Nutritional deficiency - Hypoplastic or aplastic anemia - Bone marrow infiltration like leukemia & other malignancies, - Myelodysplastic syndrome
- Dyserythropoietic anemia
• Increased physiologic requirement - Extracorpscular - alloimmune & isoimmune hemolytic
anemia, microangiopathic anemias, infections, hypersplenism,
- Intracorpsular defect – Red cell membranopathy i.e. congenital
spherocytosis,elliptocytosis
– Hemoglobinopathy like HbS, C,D,E etc. Thalassemia syndrome
– RBC enzymopathies like G6PD deficiency, PK deficiency etc.
ETIOLOGICAL CLASSIFICATION OF ANEMIA
Differential of Anemia
lead poisoning
chronic d isease
thalssem ia
iron def
Hypochrom ic, m icrocytic
Renal d isease
Transient erythroblastopeniaof childhood
Ca/BM failure
chronic d is
Norm ochrom ic,norm ocytic
Drugs (etoh)
Down Syndrom e
Liver d isease
B12/fo late def
Macrocytic
Inadequate response (RPI<2)
Im m une Hem olytic anem ia
extrinsic factors(D IC ,HUS,TTP)
m em branopathy
enzym opathy
hem oglobinopathy
Adequate response (RPI>3)r/o b lood loss/hem olytic d is
Hgb, ind ices, retic count and sm ear
Follow-up
• Re-check CBC 4-6 weeks (to confirm response)• Continue iron 3-4 months (to replace stores)• Generally, should not need treatment for more than
5 months unless there are ongoing losses• If no improvement on adequate iron therapy,
consider evaluating the child for lead poisoning or thalassemia
PHYSIOLOGIC ADJUSTMENTS
• increased cardiac output • increased oxygen extraction (increased
arteriovenous oxygen difference)• shunting of blood flow toward vital organs
and tissues• the concentration of 2,3-
diphosphoglycerate (2,3-DPG) increases within the RBC
• The resultant “shift to the right” of the oxygen dissociation curve, reducing the affinity of hemoglobin for oxygen, results in more complete transfer of oxygen to the tissues
CLINICAL FATURES
• weakness • tachypnea • shortness of breath on exertion• tachycardia• cardiac dilatation• congestive heart failure • ultimately result from increasingly severe
anemia, regardless of its cause.
Serum Iron TIBC BM Iron Comment
Iron deficiency D I 0 Responsive to iron therapy
Chronic inflammatio
n
D D ++ Unresponsive to iron therapy
Thalassemia major
I N ++++ Reticulocytosis and indirect bilirubinemia
D/D of microcytic anemia:
Thalassemia minor N N ++
Elevation of A of fetal hemoglobin, target cells, and poikilocytosis
Lead poisoning N N ++ Basophilic stippling of RBCs
Sideroblastic I N ++++
Ring sideroblasts in marrow
Serum iron
TIBC BM Iron
Comment
PYROPOIKILOCYTE
• RBCs w/c are extremely sensitive to heat
HEMOLYTIC ANEMIA- INTRACORPUSCULAR
Hereditary spherocytosisHereditary elliptocytosisHemoglobinopathiesThalassemiasCongenital dyserythropoietic anemiasHereditary RBC enzymatic deficienciesParoxysmal nocturnal hemoglobinuriaSevere iron deficiency
HEMOLYTIC ANEMIA- EXTRACORPUSCULAR
Physical agents: Burns, cold exposureTraumatic: Prosthetic heart valves, graft rejectionChemicals: Drugs and venomsInfectious agents: Malaria, toxoplasmosis, leishmaniasisHepatic and renal diseaseCollagen vascular diseaseMalignanciesTransfusion of incompatible bloodHemolytic disease of the newbornCold hemagglutinin d/sAutoimmune hemolytic anemia
Thrombotic thrombocytopenic purpura (TTP)Hemolytic uremic syndrome (HUS)
DIC
Alterations of Hbs by disease:• Gower Hb in few newborns: Trisomy 13/15• Hb Portland: stillborns with homozygous α-thalassemia• Elevated HbF (>2 %): β-thalassemia trait homozygous thalassemia Hb SS, Hb SC preterm infants treated with human recombinant
EPO others: hemolytic anemias leukemia aplastic anemia
• Hb A2 > 3.4 %: β-thalassemia trait
megaloblastic anemia• Decreased Hb A2 :IDA
α-thalassemia
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