APPROACH TO ANEMIA

Lecturer. Dr. Joel Solórzano Romero

 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
 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
 ↓oxygen carrying capacity
 Shift to right
 ↑ 2,3-DPG
 ↑ Cardiac output
 Circulation shifts to critical areas
 ↑ RBC production
 ↑ Erythropoietin
 Left shift on blood smear
 ↑ Reticulocyte count
8
 Compensating mechanisms in
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
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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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 Diagnosis and investigation:

 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 history and physical
examination

 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
Clinical symptoms and findings of anemia

 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
Clinical symptoms and findings of anemia
Cardiovascular 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
Clinical symptoms and findings of anemia
Central nervous system

 Headache
 Faintness
 Giddiness
 Tinnitus
 Decreased concentration ability
 Drowsiness,decreased muscle strength
 Clouding of consciousness
 Symptoms are more prominent in older patients
 Paresthesias:Vitamin B12 deficiency (or other).
Clinical symptoms and findings of anemia

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 RPIwww.drsarma.in
is 2.25
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 6.5www.drsarma.in

-9µ >9µ
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)
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 BM Fe Stain Absent Fe
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 www.drsarma.in

– Associated with infections

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 spanwww.drsarma.in Decreased
 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 www.drsarma.in
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… 46
 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 ?
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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.
 If retic. count is ↑- HA work up; Hb EP, spl. tests
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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
CURE
ORAL
– 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
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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