ANEMIA DISCUSSION

Lt col Ajay Kumar

What is Anaemia ?

Important to remember
 Anemia is a clinical sign of disease
 It is not a single disease by itself
 Need to look for the underlying cause !
 Anemia
 Anemia is generally defined as a
hemoglobin <13.5 g/dL in men or
hemoglobin <11.5 g/dL in women.
(WHO definition)
 The RBC Lineage

Let us meet the Grand

Parents !
 |Red cell precursors and the
Partners in Global Health Education sequence of erythropoiesis

marrow Pronormoblast: This is the earliest and largest cell with a

large nucleus and no haemoglobin.

Normoblasts Fundamentally they reduce in cell size

but increase the haemoglobin concentration in the
cytoplasm. The nucleus proportionally decreases until
it is extruded before the cell is released in to the blood.

3.4. Reticulocytes: Considered the “teenagers” of the

the life cycle! This is the FINAL stage of development
before full maturation , anucleate and contain
roughly 25% of the final haemoglobin total. They
reside mostly in the marrow

3.5 Erythrocyte: after 1 week the mature

blood erythrocyte emerges with no organelles and high
haemoglobin content.
Partners in Global Health Education | the erythrocyte: an overview

START HERE To achieve these functions the red Flexibility: t due to the
cell has several unique properties…. flexible membrane
Function and shedding of the
The primary function of the nucleus.
erythrocyte is the carriage of oxygen
from the lungs to the tissues and CO2
from the tissues to the lungs.

Lifespan: Because the fully developed

red blood cell has no nucleus the cell
cannot divide or repair itself. The
lifespan is therefore relatively short Strength: it has a
(120 days). FINISH HERE strong but flexible
membrane able to
withstand the
recurrent shear forces
Haemoglobin content: Oxygen involved in the
transport due to its affinity for O2. circulation of blood.
Biconcave shape: increases surface
area available for gaseous
exchange.
 | Erythropoiesis
Partners in Global Health Education

3. EPO
continues to
stimulate Erythroid
primitive precursors
erythroid cells Stem
Bone marrow
(red blood cells) cells
in the bone
marrow and
induce
maturation.

Red blood cells in

2. EPO stimulates erythropoietin circulation
stem cells within
the bone marrow
which differentiate
into erythroid
precursors.
Kidney
1: Erythropoietin (EPO),
4. There is no store of EPO. The production of
a growth factor, is
erythropoietin is triggered by tissue hypoxia
synthesized primarily
(oxygen tension sensed within the tubules of the
(90%) from peritubular
kidney) and stops when oxygen levels are normal.
cells of the kidneys (renal
cortex).
• List the key components of erythropoiesis (red cell production)
Partners in Global Health Education |haematinics
Erthropoiesis is also regulated by the availability of haematinics
• So what exactly are the haematinics? These are the key micronutrients that must be present if a red
blood cell and its haemogoblin are to develop in a normal fashion.

• These major micronutrients, provided in a balanced diet, are iron, vitamin B12 and folate

Iron:

. In iron deficiency, red cells undergo more divisions than normal and, as a result, are smaller
(microcytic) and have a reduced haemoglobin content (hypochromic). Iron deficiency is the leading
cause of anaemia worldwide.

Vitamin B12 (cobalamin) and folate (pteroylglutamic acid):

These are key building blocks for DNA synthesis and essential for cell mitosis. 2. In haematinic
deficiency, DNA replication is limited and hence the number of possible cell divisions is reduced leading
to larger red cells being discharged into the blood i.e. less DNA, less divisions and larger cells. This leads
to enlarged,cells or megaloblasts in the marrow and macrocytic red cells in the blood.
Partners in Global Health Education classification of anaemia
Essentially there are two ways to classify anaemia, by red
cell size (morphological classification) or by cause
(aetiological classification). Both have their purpose and
both need to be fully understood to gain a rounded
understanding of anaemia.

Morphological classification Aetiological classification

classification for establishing a This classification is based on cause
differential diagnosis of anaemia. and illuminates the pathological
process underlying anaemia.
It is done by examining red cells in a
blood stained smear and by
automated measurements of red cell
indices
Partners in Global Health Education | red cell indices
These are the key measures of red cell indices. They relate to the haemoglobin content and
size of the red blood cells.

MCV: Mean cell volume; the average volume of the red cells. MCV does not provide
an indicator of either haemoglobin concentration within the cells, or the number of red cells. It enables
us to categorize red cells into the following;

Microcytic (MCV <80fL) a small red blood cell.

Normocytic (MCV of 80-99fL) a normal size red blood cell.
Macrocytic (MCV > 99fL) a large red blood cell.

This is a key index that is used daily in medical settings across the world to categorize the type of
anaemia present.

MCH: Mean corpuscular haemoglobin ( normal range 26.7-32.5pg/cell): the

average haemoglobin content of red blood cells. Cells with a reduced haemoglobin content are
termed hypochromic and those with a normal level are termed normochromic (see below).

RDW: Red cell distribution width; an index of the variation in sizes of the red cell population
within an indiviual. This will be raised if two red cell populations are present. Occasionally useful if there
is doubt about multiple causes of anaemia. A common cause for an increased RDW is the presence of
reticulocytes.

Normochromic implies normal staining of the cells in a thin blood film. The central
area of pallor is normally about 1/3 of the cell diameter

Hypochromic indicates reduced staining with increase in the central area of pallor
Partners in Global Health Education |interpretation of red cell indices

Microcytosis & Normocytosis & Macrocytosis &

hypochromia normochromia megaloblastosis

Microcytic Normocytic normochromic Macrocytic megaloblastic

abnormally small red blood cells. anaemia develops when there is a red blood cells have an unusual misshapen
Microcytic anemia is not caused decrease in the production of normal appearance, which is due to defective
by reduced DNA synthesis. red blood cells. synthesis of DNA.

Hypochromic Normocytic In clinical practice megaloblastic anaemia is

hypochromic cells due to a Many processes causing anaemia do almost always caused by a deficiency of
not effect the cell size or haemoglobin vitamin B12 or folate which are key building
failure of haemoglobin concentration within cells. blocks in DNA synthesis.
synthesis.

Pathologies;
• Iron deficiency; i.
• thalassemia's.
• sickle cell disease
Pathologies;
• anemia of chronic disease (some)
• aplastic anemia
• Haemolysis: a increased destruction (some)
• Hemolysis ;or loss of red blood
• pregnancy/fluid overload: an inbalance or
an increase in plasma volume compared
to red cell production
 Peripheral Blood Smear
(In the Diagnosis of Anemia)

► Look for:
 Neutropenia
 Thrombocytopenia
 Hypochromia
 Size and shape of RBCs
 Unusual leukocytes (hypersegmentation)
 Red cell inclusions: basophilic stippling,
Howell-Jolly bodies…

12
 Reticulocyte Count
(In the Diagnosis of Anemia)

► Useful in determining response and potential of bone

marrow.
►
► Reticulocytes are non-nucleated RBCs that still contain RNA.
.
► Normal range is 0.5-2.0% of all erythrocytes.

► If bone marrow responding to anemia, should see increases

in retic count.

13
Bone Marrow
(In the Diagnosis of Anemia)

► Bone marrow aspiration and biopsy

are important diagnostic tools in the
determination of anemia.

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Partners in Global Health Education | morphological classification of anaemia

Anaemia type Microcytic Normocytic Macrocytic

hypochromic normochromic
Megaloblastic

Red cell MCV < 80 fl normal MCV > 98 fl

indices MCH < 27 pg/L

Iron deficiency Haemolysis

Common Folate deficiency
examples Thalassaemia Chronic disease
B12deficiency
Sideroblastic Marrow infiltration
 |
Partners in Global Health Education |classification of anaemia based on pathology

anaemia

Increased Dilution of red cells Failure of

destruction of red Loss of red cells by increased production of red
cells (haemolytic due to bleeding plasma volume (e.g. cells by the bone
anaemia hypersplenism) marrow

Reduced bone Nutritional Ineffective red cell

marrow erythroid (haematinic) formation
cells deficiency • Chronic inflam.
• aplastic anaemia • Iron • Thalassaemia
Acquired / Inherited / • Leukaemia or • vitamin B12 • renal disease
outside cell inside the cell malignancy • folate

Abnormal red Abnormal red

Non- Abnormal
immune cell cell
immune haemoglobin
membrane metabolism

• Autoimmune
warm
• Autoimmune • Malaria • Pyruvate
cold • Burns Thalassaemia
• Sperocytes kinase
• Adverse • Mechanical deficiency
drug heart valve • Sickle cell
• Elliptocytes • G6PD
reaction • Hypersplenism anaemia
deficiency
• Haemolytic • PNH
disease of
the newborn
CAUSES
 SIGNS OF ANAEMIA
 Brittle nails
 Koilonychia (spoon shaped nails)
 Atrophy of the papillae of the
tongue
 Angular stomatitis
 Brittle hair
 Dysphagia and Glossitis
 Plummer vinson/kelly patterson
Diagnostic Approach
 Diagnostic Approach
Diagnostic Approach-History
 Age : Iron def rare without blood loss before 6 months in term
infants.

 Family Hist &Genetics:

(1)X-linked: G6PD deficiency

(2)Aut dominant: Spherocytosis

(3)Aut recessive:Sickle cell,Fanconi anemia

(4)Family member with early age of

cholecystectomy/splenectomy

(5)G6PD def: (Greeks, Blacks, Middle eastern)

Diagnostic Approach-History
 Nutrition: (1)Cows milk diet:iron def.
(2)Strict vegetarian:Vit B12 def.
(3)Goats milk: Folate def.
(4)Pica: Iron def.

 Drugs: (1)G6PD: oxidants (sulfa, primaquine)

(2)Immune mediated hemolysis(penicillin) (3)Bone
marrow suppression(chemotherapy)
Diagnostic Approach-History
Diarrhoea-Malabsorption of VitB12/E/Fe.
Inflammatory bowel disease and anemia of chronic
disease with or without blood loss.
Milk protein intolerance induced blood loss
Intestinal resection

Infection: Giardia:iron malabsorption .

Intestinal bacterial overgrowth:Vit B12 def
Fish tapeworm:Vit B12 def
-EBV,CMV,Parvovirus:BMsuppression
Mycoplasma,Malaria:hemolysis
Physical exam reveals presence and
potential causes of anemia
 Fever-acute infection,intravascular disease,collagen
vascular disease
 Jaundice suggests hemolysis
 Petechia & Purpura—bleeding tendency
 Hypertension & edema-renal disease
 Hepatosplenomegaly and lymphadenopathy—infiltrative
disease
 Growth failure or poor wt. gain—Anemia of chronic
disease or organ failure
 Examine stool for blood
Laboratory Evaluation
 Hematology: Complete Blood Count, Retic count,
Peripheral smear, ESR, G6PD,
, BM aspiration
 Biochemistry: LFT, UE, RFT, S.Ferrtin, Iron, VitB12,
Folate,
 Urinalysis, microscopy, culture/sensitivity
 Stool exam. for ova, parasites, occult blood
 Endoscopy: upper and lower bowel
 Imaging: US Abdomen, Skeletal radiographs
 Tissue biopsy: skin, lymph node,
Iron Deficiency

 Can result from:

 Pregnancy/lactation
 Normal growth
 Blood loss
 Intravascular hemolysis
 Gastric bypass
 Malabsorption
 Iron is absorbed in proximal small bowel; decreased
abosrption in celiac disease, inflammatory bowel
disease
 May manifest as PICA
 Tendency to eat ice, clay, starch, crunchy materials
 May have pallor, koilonychia of the nails.
 Peripheral smear shows microcytic, hypochromic
red cells with marked anisopoikilocytosis.
IDA – Special Tests

Iron related tests Normal IDA

Serum Ferritin (pmo/L) 33-270 < 33
TIBC (µg/dL) 300-340 > 400
Serum Iron (µg/dL) 50-150 < 30
Saturation % 30-50 < 10
Bone marrow Iron ++ Absent
 Management
Care Objectives
 Determine the Cause of Iron
Deficiency
 Aim of Treatment
 Normalize hemoglobin levels and red
cell indices; replenish iron stores.
 Individualize disease-specific
management depending on
underlying cause.
 Lifestyle Management
It is recommended that patients with iron
deficiency receive dietary advice .
 management
Complimentary parasite control
measures
 Anti-helminthic therapy with 400 mg of single
dose of albendazole is given to eliminate hook
worms before the initiation of iron and folic acid
therapy.
 Child -
<2yrs-200mg/day single dose

 Pregnancy-
Albendazole is contraindicated in first
trimester,can be administered in second or third
trimester.
RECOMMENDED DIETARY Mg/DAY
ALLOWANCE
Men Adult 8 mg
Women Adult (age 50 on) 8 mg

Pregnant 27 mg

Lactating 9 mg to 10 mg

Adolescents (ages 9 to 18)

Girls 8 mg to 15 mg
Boys 8 mg to 11 mg

Children (birth to age 8) Ages 10 mg

4 to 8
Infants (7 months to 1 year) 11 mg
Infants (birth to 6 months) 0.27 mg
 TREATMENT OF MILD
&MODERATE
GROUP DOSAGE/day

Children 2-5 years 20-30 mg iron

Children 6-11 years 30-60 mg iron

Adolescents and adults 60 mg iron

 Anemia will correct within 2 to 4 months if appropriate iron

dosage.

 Continue iron therapy an additional 4 to 6 months (adults)

after the hemoglobin normalizes to replenish the iron stores.
TREATMENT OF PREGNANT
WOMEN
Prevalence of anemia in Dose Duration
pregnancy
>40 % in population 60 mg iron + 400 ug folic 6 months in pregnancy,
acid daily and continuing to 3
months postpartum
NON PHARMOCOLOGICAL
MANAGEMENT:
 Tea and coffee inhibit iron absorption when consumed with
a meal or shortly after a meal.

 Vitamin C (ascorbic acid) is also a powerful enhancer of

iron absorption

 Germination and fermentation of cereals and legumes

improve the bioavailability of iron by reducing the content
of phytate, a substance in food that inhibits iron
absorption.

 Promote and support exclusive breastfeeding for about 6

months
Vitamin B12 Deficiency

 Macrocytic anemia
 Cobalamin level < 200 pg/mL

 Vit. B12 is needed for DNA synthesis

 Binds to intrinsic factor in the small bowel in order to be

absorbed

 Deficiency can result in neuropsychiatric symptoms

 Spastic ataxia, psychosis, loss of vibratory sense,
dementia

 Smear shows macrocytosis with hypersegmentation of

polymorphonuclear cells.
Vitamin B12 Deficiency
Treatment of Vitamin B12
Deficiency
 Vitamin B12 – 1000 micrograms intramuscularly
monthly
-OR-
 Vitamin B12 – 1000-2000 micrograms po QDaily
Anemia of Chronic Disease

 Usually normocytic, normochromic (but

can become hypochromic, microcytic over
time)
 Occurs in people with inflammatory
conditions such as collage vascular disease,
malignancy or chronic infection.
 Iron replacement is not necessary
 May benefit from erythropoietin
supplementation.
Hemolysis

 Hemolysis is defined as the premature destruction

of red blood cells, from whatever cause.

The simplest tests are

(a) Raised reticulocyte count
(b) Raised indirect (unconjugated) bilirubin
(c) Raised serum LDH
.
Hemolysis

Principal causes
Inherited abnormalities
* Membrane (Hereditary Spherocytosis)
* Hemoglobin (Sickle Cell Anemia)
* Enzymes (Glucose-6-phosphate
dehydrogenase (G6PD) deficiency)
THALASSEMIA
 Normal Hb is a tetramer of 2 alpha and
2 beta chains
 Alpha-thalassemia:decrease or total lack
of alpha globin synthesis
 Beta-thalassemia:decrease or total lack
of beta globin synthesis
THALASSEMIA-therapy
 Red cell transfusion 3-4 weekly-Hb 9-10
 Chelation therapy with desferrioxamine
 Splenectomy if transfusion >200ml/kg/yr
 Folic acid 5mg daily
 Penicillin prophylaxis to all splenectomised
 Pneumococcal and Hib vaccine before sply.
 Bone marrow transplantation
SICKLE CELL DISEASE
 Anemia:,onset at 3-4 mo
 Aplastic crisis:parvo virus B12
 Dactylitis:Hand foot syndrome(infant)
 Painful crisis:muscle,bone,bone marrow,lung,
intestines
 Cerebrovascular accidents
 Acute chest syndrome:infection,infarction,emb
THERAPY
 Blood transfusion

 Pain crisis:IVF,analgesia with narcotics,NSAIDs

 Acute chest syndrome:O2,judicial use of

analgesics&fluids,antibiotics,PRBC

 Stroke:O2,fluids,exchange transfusion

 Hydroxyurea:decrease number&severity of Vasoclusive episode

 Bone marrow transplantation
Anaemia - Summary

 If Hb% is low – Do not start on Iron straight away

 Ask for RCC, Hematocrit – Derive MCV, MCH, MCHC
 Order for Reticulocyte count – Is RPI < 2 % or > 2

 If hypo proliferative – Microcytic or Macrocytic? (MCV, RDW)

 If microcytic – IDA or others – Spl. Iron tests, BM Iron
 If macrocytic – Megaloblastic (B12, FA)
 If normocytic – Anaemia of chr. Disease – Liver, , Ca
 Peripheral smear study for RBC size, shape, colouration etc.
 If retic. count is ↑- HA work up; Hb EP.
Well done!
You have come to the end of SESSION
A normal red blood cell has an average lifespan of 80 days

Erythropoietin is reduced in chronic hypoxia

An adult male with a haemoglobin concentraion (Hb) < 11.5 g/dl is anaemic.

The respiratory system is the main physiological compensator in anaemia.

Vitamin B12 is absorbed in the jejunum.

Folate and vitamin B12 are key building blocks of haemoglobin.

Chronic anaemia and malignancy prevent haem production.

Koilonychia, glossitis and angular stomatitis are all general signs of iron def. anaemia.

Microcytosis is MCV < 90fL

In vitamin B12 deficiency you would expect the MCV to be >99fL

Adult haemoglobin is composed of 2 alpha and 2 beta globin chains.

Increased reticulocytes is a key feature of a haemolysis.

Thank You