Approach To

Anemia
DR. BAHEEG ALMURAISI
 Topic

Definition
Definition

Epidemiology
Epidemiology

Clasification
Clasification

Clinical
ClinicalManifestations
Manifestations

diagnosis,
diagnosis,treatment
treatment
DEFINITION OF ANEMIA
From Greek meaning “without blood” •Condition where capacity of blood
to transport oxygen to tissues is reduced
Anemia is operationally defined as a reduction in one or more of the
major RBC measurements: Decreased hemoglobin, RBC count, and
hematocrit.
Hb level of a patient which is below the normal ranges of that age and
sex.
For adults:
WHO criteria define anemia as hemoglobin level lower than 12 g/dL in
women and 13 g/dL in men

Anemia is not a disease but a manifestation of disease

 BACKGROUND

• Iron deficiency is the most common form of malnutrition in the world. Iron deficiency
anemia is highly prevalent in less-developed countries but also remains a problem in
developed countries where other forms of malnutrition have already been virtually
eliminated.

• The prevalence of anemia, defined by low hemoglobin or hematocrit, is commonly used to

assess the severity of iron deficiency in a population
• Consecuence Of Anemia
• Reduced Levels Of Hb Results With Reduced Oxygen
Delivery To Tissues , Leading To Tissue Hypoxia.
• The Symptoms And Findings Of Anemia Concern Many
Different Systems/Organs Due To The Widespread Nature
Of Hypoxia.
Compensating mechanisms in anemia

 The rate of blood circulation and cardiac output increases.

 An increase in plasma volume maintains total blood volume
in normal or near normal ranges.
 Redistribution of blood flow.
Physiological Response
1. ↓oxygen carrying capacity

2. Shift to right

3. ↑ 2,3-DPG

4. ↑ Cardiac output

5. Circulation shifts to critical areas

6. ↑ RBC production

7. ↑ Erythropoietin

8. Left shift on blood smear

9. ↑ Reticulocyte count

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 Compensating Mechanisms İn
Anemia:
The release of oxygen to the tissues is increased (reduced
oxygen affinity of Hb)
Volume Changes/Acute Bleeding
And Anemia
1 2 3 4 5

Increased
normal Dehydration Acute blood Chronic
plasma
Hct:Increased loss(early) anemia
Hct (a/b%):Normal volume
Hct: Low Hct:unchanged Hct: Low
Etiopathogenic Classification Of Anemias
• Decreased RBC production( Hypoproliferative)
A. Defective hemoglobin synthesis
 Fe deficiency

 B12 deficiency

 Folate deficiency
B. Impaired bone marrow or stem cell function, as in leukemia Erythrocyte loss :

Increased RBC destruction e.g hemolytic anemia.

Bleeding

• Combination of the two (sometimes called “ineffective erythropoiesis”)

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MORPHOLOGICAL
CLASSIFICATION OF ANEMIAS

Morphological based on sizes and color of RBCs

• Normochromic Normocytic
• Hypochromic Microcytic
• hyperchromic Macrocytic

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 QUANTITATIVE
CLASSIFICATION OF ANEMIAS
Quantitatively by:
• Hematocrit
• Hemoglobin
• Blood cell indices
• Reticulocyte count

► On basis of H&H, anemia can be classified as mild, moderate, or severe.

► On basis of duration of onset, anemia can be classified as either chronic or
acute.
► Classified as moderate (Hb 7-10 g/dl) or severe (Hb <7g/dl).

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DİAGNOSİS AND İNVESTİGATİON:
Is the patient anemic?
What is the type of anemia?
What is the cause of anemia?
The symptoms and findings are related to anemia itself or to the underlying
. disease that causes anemia
CLINICAL DIAGNOSIS

• Made by combination of factors including: patient

history, physical signs and changes in hematologic
profile (CBC).
• Signs and symptoms usually non-specific: fatigue,
weakness, gastrointestinal symptoms (nausea,
constipation and diarrhea), shortness of breath -
especially after exertion.
• Physical signs of anemia are usually not specific for
the cause.

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SOME OTHER EXAMPLES FOR
HİSTORY AND PHYSİCAL
EXAMİNATİON

The duration of symptoms (acute/insidious)

Bleeding ? Nose/skin/urine/mens/stool etc
Family history
• Anemia, gall stones and splenectomy
• Bleeding disorder
Occupation, hobbies,dietary history,alcohol or drug
use,travel history etc (toxic/infectious contacts)
Ask for skin and hair/nail changes
CLİNİCAL SYMPTOMS AND
FİNDİNGS OF ANEMİA

Anemia leads to two symptom complexes

Tissue hypoxia
Compensatory attempts
Fatigue, weakness
• Tiredness, lassitude, reduced exercise tolerence
• Generalized muscular weakness
Pallor /skin or mucous membranes
Pallor (paleness):
Look at
• Mucous membranes of mouth and pharynx
• Conjunctivae,lips, nail beds,palms
• Creases of the palms lose their pink colour when the Hb < 7g/dL
In pernicious anemia there is a lemon yellow pallor.
Pallor + mild scleral icterus suggests hemolytic anemia.
Pallor+ petechiae suggests severe bone marrow failure
Some other skin/mucosal changes
• Premature graying of hair:pern.anemia
• Hair loss and fragility + spooning of the nails:iron
deficiency
• Chronic leg ulcers:Sickle cell or other hemolytic anemia
• Glossitis/burning sense :Pern. anemia, iron deficiency(rare)
• Chelitis(angular stomatitis):iron def.
• Siideropenic dysphagia: iron def.
• Painful ulcerative mouth lesions: aplastic anemia/leukemia
CLİNİCAL SYMPTOMS AND
FİNDİNGS OF ANEMİA
CARDİOVASCULAR SYSTEM(1)

• Palpitation and dyspnea (during activity)

• Angina pectoris
• Claudicatio intermittans

• Murmurs: Mid systolic (rarely diastolic) , mainly

pulmonary valvular or apical
• or over major peripheral arteries
• or jugulary veins
CLİNİCAL SYMPTOMS AND
FİNDİNGS OF ANEMİA
CENTRAL NERVOUS SYSTEM

1. Headache
2. Faintness
3. Giddiness
4. Tinnitus
5. Decreased concentration ability
6. Drowsiness,decreased muscle strength
7. Clouding of consciousness
8. Symptoms are more prominent in older patients
9. Paresthesias:Vitamin B12 deficiency (or other).
CLİNİCAL SYMPTOMS AND
FİNDİNGS OF ANEMİA

Reproductive system
Menstrual changes:
• Amenorrhea ,
• Menorrhagia(mostly a cause of anemia)
Loss of libido
Koilonychia - spoon shaped nail
 glossitis Angular stomatitis

Nutritional deficiency anemia

 BASIC HEMATOLOGIC LAB TESTS

• • Complete blood count (CBC) –

• Amount of hemoglobin – Number, size, and shape of red blood cells (RBCs) – Number of white
blood cells (WBCs) and platelets – +/- automated WBC differential
• • Manual differential/manual peripheral smear review
• • Abnormalities that fall outside of established parameters result in manual review
NORMALS

COMPONENT NORMAL RANGES

WBC 4.8-10.8 x 103/μL
RBC Male 4.7-6.1 x 106/μL; Female 4.2-5.4 x 106/μL
Hgb Male 14-18 g/dL; Female 12-16 g/dL
Hct Male 42-52%; Female 37-47%
MCV 80-100 fL
MCH 27-31 pg
MCHC 32-36%
RDW 11.5-14.5%
Plt 150,000-350,000/μL
Retic 0.5-2.0%

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HYPOPROLIFERATIVE
ANAEMIAS
Failure of cell
maturation
Nuclear Cytoplasmic
breakdown breakdown

Folate or B12 deficiency Haem defect Globin defect

Defective DNA synthesis Fe Phorph Sickle cell A

Megaloblastic Anaemia IDA, SA Thalassemia

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RETICULOCYTE
PRODUCTION INDEX
For example the RPI is calculated as
follows
Reticulocyte count 9%
Hb content 7.5 g%
1. Correction for Anaemia
= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %
2. Correction for increased life span
4.5 ÷ 2 = 2.25 %
3. Thus, the RPI is 2.25

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ANAEMIA

Hb% < 12, Hct < 38%

Hypoproliferative Hemolytic

RPI < 2 RPI > 2

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MEAN CELL VOLUME (MCV)

RBC volume (rather) is measured by

The Mean Cell Volume or MCV and RDW
MCV

Microcytic Normocytic Macrocytic

< 80 fl 80 -100 fl > 100 fl

< 6.5 µ 6.5 - 9 µ >9µ

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ANAEMIA WORKUP - MCV

MCV

Microcytic Normocytic Macrocytic

Iron Deficiency IDA Chronic disease Megaloblastic anemias
Chronic Infections Early IDA Liver disease/alcohol
Thalassemias Hemoglobinopathies Hemoglobinopathies
Hemoglobinopathies Primary marrow disorders Metabolic disorders
Sideroblastic Anemia Combined deficiencies Marrow disorders
Increased destruction Increased destruction
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MICROCYTIC ANAEMIAS

MCV < 80 fl Serum Iron TIBC BM Perls stain

Iron Def. Anemia ↓↓ ↑↑ 0
Chronic Infection ↓↓ ↓↓ ++
Thalassemia ↑↑ N ++++
Hemoglobinopathy N N ++
Lead poisoning N N ++
Sideroblastic ↑↑ N ++++
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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
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IDA SUMMARY

Microcytic MCV < 80 fl, RBC < 6 µ

RDW Widened and shift to left
Hypochromic MCH < 27 pg, MCHC < 30%
RPI <2
Retic. count May be > 2 %
Serum ferritin Very low < 30 (p mols/L)
TIBC Increased > 400 (µg/dL)
Serum Iron Very low < 30 (µg/dL)
BM Fe Stain Absent Fe
Response to Fe Rx. Excellent
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MACROCYTIC ANAEMIAS

A. Megaloblastic Macrocytic – B12 and

Folate↓
B. Non Megaloblastic Macrocytic Anaemias
1. Liver disease/alcohol
2. Hemoglobinopathies
3. Metabolic disorders, Hypothyroidism
4. Myelodystrophy, BM infiltration
5. Accelerated Erythropoesis - ↑destruction
6. Drugs (cytotoxics, immunosuppressants, AZT,
anticonvulsants)

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PERNICIOUS ANAEMIA -
TONGUE

Bald, smooth, lemon

yellowish red tongue

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• Non-specific signs and symptoms of anemia • Macrocytic anemia • Relatively low
reticulocyte count • Hypersegmentation of neutrophils • Mild thrombocytopenia and/or
neutropenia • Megaloblastic changes in marrow • Neurological findings (B12 deficiency
only): loss of position sense, ataxia, psychomotor retardation, seizures

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NORMOCYTIC ANAEMIAS

1. Chronic disease
2. Early IDA
3. Hemoglobinopathies
4. Primary marrow disorders
5. Combined deficiencies
6. Increased destruction
7. Anaemia of investigations -ICU

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 EVALUATION OF
NORMOCYTIC ANEMIA
PB smear, reticulocyte count
• Screen for liver, endocrine, renal disease
• Iron studies
• Bone marrow biopsy

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HEMOLYTIC ANAEMIA

Anemia of increased RBC destruction

– Normochromic, normocytic anemia
– Shortened RBC survival
– Reticulocytosis – due to ↑ RBC destruction
Will not be symptomatic until the RBC life span is
reduced to 20 days – BM compensates 6 times

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 HEMOLYTIC ANEMIA

• Inherited hemolytic anemia .

• Membrane defects (eg. hereditary spherocytosis)
• – Globin defects (eg. Sickle cell anemia)
• – Metabolic disorders • Glucose-6 phosphate deficiency Acquired hemolytic
anemia Immune mediated – Microangiopathic hemolytic anemia
• – Associated with infections
• – Paroxysmal nocturnal hemoglobinuria

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FINDINGS IN HEMOLYTIC
ANAEMIA
Reticulocyte count and RPI Increased
Serum Unconjugated Bilirubin Increased
Serum LDH 1: LDH 2 Increased
Serum Haptoglobin Decreased
Urine Hemoglobin Present
Urine Hemosiderin Present
Urine Urobilinogen Increased
Cr 51 labeled RBC life span Decreased
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 TESTS TO DEFINE
THE CAUSE OF HEMOLYSIS
1. Hemoglobin electrophoresis

2. Hemoglobin A2 (βeta-Thalassemia trait)

3. RBC enzymes (G6PD, PK, etc)
4. Direct & indirect antiglobulin tests (immune)
5. Cold agglutinins
6. Osmotic fragility (spherocytosis)
7. Acid hemolysis test (PNH)
8. Clotting profile (DIC), B12, Fe, TIBC, Folate Levels
9. Bone marrow aspirates and smear evaluation may also be needed

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PERIPHERAL BLOOD SMEAR
(IN THE DIAGNOSIS OF ANEMIA)
Very useful in diagnosing and classifying anemias
Look for:
• Neutropenia
• Thrombocytopenia
• Hypochromia
• Size and shape of RBCs
• Unusual leukocytes (hypersegmentation)
• Red cell inclusions: basophilic stippling, Howell-Jolly bodies…

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 ANAEMIA WORKUP -
PERIPHERAL SMEAR STUDY
• Are all RBC of the same size ?
• Are all RBC of the same normal discoid shape ?
• How is the colour (Hb content) saturation ?
• Are all the RBC of same colour/ multi coloured ?
• Are there any RBC inclusions ?
• Are intra RBC there any hemo-parasites ?
• Are leucocytes normal in number and D.C ?
• Is platelet distribution adequate ?
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 Anaemia Diagnosis -Algorithm

Anaemia Suspected

Thorough Clin, Bleed Hb%, RCC, Hct Decreased

Ca, Leukemia, Ulcer

RPI, Retic count <2 RPI, Retic count >2
Identify the cause

MCV, MCH, MCHC, PSE Hemolytic Anaemia

Microcytic hypochromic Macrocytic hypo/normo Coombs DAT, IDAT

Iron Def. Anaemia Megaloblastic Normoblastic Hb electrophoresis

Ferritin, TIBC, BM Fe Folate defici. ALD, CLD, Drug Osmotic fragility

Thalassemia, Hb pathy B12 def., PA Chr. Renal dis. Acid hemolysis

Sederoblastic Anaem. Hypothyroid Cold agglutinins

Chr. Infection, Lead BM infiltration Coagulopathy, DIC

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 ANAEMIA DIAGNOSIS -
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%
Thoroughly look for blood loss – acute / chronic / occult
Is it hypo-proliferative or hemolytic or hemorrhagic anaemia
If hypo proliferative – Microcytic or Macrocytic? (MCV, RDW)
If microcytic – IDA or others – Spl. Iron tests, BM Iron
If macrocytic – Megaloblastic (B12, FA) or Normoblastic BM
If normocytic – Anaemia of chr. Disease – Liver, MRD, Ca
Peripheral smear study for RBC size, shape, colouration etc.
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retic. count is ↑- HA work up; Hb EP, spl. tests
 TREATMENT OF ANEMIAS
• Treated according to cause; Should know cause before beginning treatment.
• Patient can have more than one cause of anemia.
• Must use diagnostic tests to determine cause(s).
• Do diagnostic tests before transfusions, because transfusions obscure and
confuse findings.

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IRON REPLACEMENT
STRATEGIES
• Dietary iron
• Oral iron
• Parenteral iron
• Blood transfusion
 IRON DEFICIENCY ANEMIA
• ORAL CURE
– 200 mg of iron daily 1 hour before meal (e.g. 100 mg twice daily)
 PARENTERAL IRON SUBSTITUTION

– Bad oral iron tolerance (nausea, diarrhoea)

– Negative oral iron absorption test
– Necessity of quick management (CHD, CHF)
– iron to be injected (mg) = (15 - Hb/g%/) x body weight (kg) x 3
– IM or IV ? (risk of anaphilactic reactions)

• Intramuscular iron — Mobilization of iron from intramuscular (IM) sites is slow and occasionally incomplete. As a result, the rise in the hemoglobin
concentration is only slightly faster than that which occurs following the use of oral iron preparations.

• Ferric carboxymaltose — is a novel stable iron complex for intravenous (IV) use which can be given at single doses of up to 1000 mg of elemental iron per week
over a recommended infusion time of 15 minutes. A number of trials have shown efficacy and safety of this agent in iron deficient patients
 B12 DEFICIENCY. TREATMENT

• Hydroxocobalamin dose of 1000 µg (1 mg) IM every day for one

week, followed by 1 mg every week for four weeks and then, if the
underlying disorder persists, as in PA, 1 mg every 3 months for life

• s/e allergic reactions; hypokalaemia

• high dose oral cobalamin is an alternative but requires much

greater patient compliance
 FOLATE DEFICIENCY
• Folic acid (1 to 5 mg/day PO) for one to four months, or until
complete hematologic recovery occurs. A dose of 1 mg/day is
usually sufficient, even if malabsorption is present.

• These doses are in excess of those recommended for disease

prevention (eg, recommended daily allowance in normal adults,
alcoholics, the elderly, prevention of neural tube defects) 200-
500mcg/day
 BLOOD TRANSFUSION

• In patients who are severely anemic at presentation, the decision

to transfuse can be a difficult one, particularly in elderly patients at
risk for congestive heart failure due to volume overload

• If the anemia is extreme and the patient is critically ill, one unit can
be given initially at a slow rate, in combination with a diuretic, if
fluid status is a concern

• In extreme circumstances, isovolemic exchange can be performed

ANAEMIA OF CHRONIC
DISEASE: ERYTHROPOIETIN

Chronic renal failure

Cytototic chemotherapy

autologous blood yield ↑

Prematurity
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