This document provides an overview of hematology and anemia. It discusses the components of blood, red blood cell development and indices, classifications of anemia, laboratory tests used in diagnosis, and the differential diagnosis of anemia types based on red blood cell morphology and etiology. Key points include that anemia is defined as low hemoglobin or red blood cell count, and anemias are caused by either inadequate red blood cell production or accelerated red blood cell destruction. Anemias can be classified as microcytic, normocytic, or macrocytic based on cell size, and have various potential underlying etiologies.
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Introduction to Hematology and Anemia
1. Introduction to Hematology
and Anemia
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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2. Blood
• Blood volume is about 8% of body weight
• 45 % is formed elements
• 55% plasma
4. FORMED ELEMENTS
• Three types:
Erythrocytes – red blood cells
Leukocytes – white blood cells
Thrombocytes – platelets – cell fragments
5. 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
6. 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
7. • 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
8. 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
9. 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
11. 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 %
12. 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
13. 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 .
14. Hgb and MCV Variability
Age Hgb mean MCV mean
birth 16.5 108
2 wk 16.5 105
2 mo 11.5 96
6mo-2yr 12.5 77
2-6 yr 12.7 80
10-12 yr 13.5 85
12-17 14 85
Adult 14-16 90
Contemporary Pediatrics, Vol 18, No. 9
15. GRANULOCYTES
• Neutrophils – phagocytes
• Eosinophils – red granules, associated with
allergic response and parasitic worms
• Basophils – deep blue granules - Release heparin
and histamine
22. 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.
23. 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
24. 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
25. 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
26. Mentzer index
• Calculated number to help differentiate
between iron deficiency vs. thalassemia if
having microcytic anemia
• MCV/RBC
• >13 iron deficiency
• <13 thal trait
27. 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) ×
28. Contd
• C. White blood cell count
• 1. Cell differential
• 2. Nuclear segmentation of neutrophils
• D. Platelet count
29. 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
31. LEPTOCYTE
Hypochromic cell with a
normal diameter and
decreased MCV
Thalassemia.
32. TARGET CELL
Hypochromic with
central "target" of
hemoglobin. Liver
disease, thalassemi
a, hemoglobin
D, postsplenectomy
33. TEAR DROP CELL
Drop-shaped erythrocyte, often microcytic.
Myelofibrosis and infiltration of marrow with tumor.
Thalassemia
34. ELLIPTOCYTE
Oval to cigar
shaped.
Hereditary
elliptocytosis,
certain anemias
(particularly
vitamin B-12 and
folate deficiency)
35. ECHINOCYTE (BURR CELL)
Evenly distributed
.
spicules on surface
of RBCs, usually 10-
30. Uremia, peptic
ulcer, gastric
carcinoma, pyruvic
kinase deficiency
36. ACANTHOCYTE
Five to 10 spicules of
various lengths and
at irregular interval
on surface of RBCs.
37. STOMATOCYTE
• Slitlike area of
central pallor in
erythrocyte. Liver
disease, acute
alcoholism, malignan
cies, hereditary
stomatocytosis, and
artifact
39. Microcytic and Hypochromic
Smaller than normal ( <7 µm
diameter
Less hemoglobin in cell.
Enlarged area of central
pallor.
40. Elongated cell with pointed ends.
Sickle cell 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 & variation in shape and variation in size
anisocytosis
41. Contd
• II. Reticulocyte count
• III. Iron supply studies
• A. Serum iron
• B. Total iron-binding capacity
• C. Serum ferritin, marrow iron stain
42. 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.
43. 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
46. 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
47. Anemia Basics
All anemias are either due to….
1. Ineffective RBC production
or
2. Accelerated destruction of the RBC
50. 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
51. Macrocytic anemia
• Megaloblastic Erythropoiesis
a) Nutritional - Folate deficiency, B12 deficiency
b) Toxic – Treatment with antifolate compound –
methotrexate,, and drugs that inhibit DNA
replication – zidovudine, phenytoin
c) Congenital disorders of DNA synthesis like
Orotic aciduria etc.
d) Malabsorption
- liver ds
- normal newborns, reticulocytosis
52. Macrocytic anemia
• Non - Megaloblastic Erythropoiesis
a) Chronic hemolytic anemia
b) Liver ds
c) Hypothyroidism
d) Diamond blackfan syndrome
53. Normocytic, Normochromic anemia
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,
osteopetrosis
2 Hemolytic anemia ( reticulocyte count high)
54. 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
55. 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
56. ETIOLOGICAL CLASSIFICATION OF 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.
57. Differential of Anemia
Hgb, indices, retic count and smear
Inadequate response (RPI<2) Adequate response (RPI>3)
r/o blood loss/hemolytic dis
Hypochromic, microcytic Normochromic,normocytic Macrocytic hemoglobinopathy
iron def chronic dis B12/folate def enzymopathy
thalssemia Ca/BM failure Liver disease membranopathy
chronic disease Transient erythroblastopenia Down Syndrome extrinsic factors
of childhood (DIC,HUS,TTP)
lead poisoning Renal disease Drugs (etoh) Immune Hemolytic anemia
58. 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
59. 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
60. 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.
61. D/D of microcytic anemia:
TIBC BM Iron Comment
Serum Iron
Iron deficiency D I 0 Responsive to iron
therapy
Chronic D D ++ Unresponsive to iron
inflammation therapy
Thalassemia I N ++++ Reticulocytosis and
major indirect
bilirubinemia
62. Serum iron TIBC BM Comment
Iron
Elevation of A of fetal
Thalassemia minor N N ++ hemoglobin, target cells,
and poikilocytosis
Lead poisoning N N ++ Basophilic stippling of RBCs
Sideroblastic I N ++++ Ring sideroblasts in marrow