An overview about approach to diagnosis of anemia for new learners. It is not all about approach to anemia, approach to anemia really needs a lot of knowledge about each groups of anemia such as microcytic, normocytic and macrocytic anemia.

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Approach to
Anemia
By: Merwais Azizyar
27.09.1398
Approach to Anemia

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Approach to
Anemia
 By the end of this session, we will be able to:
 Define Anemia and cause of Anemia
 The findings associated with anemia
 Approach to diagnosis
 Conclusion
General Objectives

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Approach to
Anemia
 A reduction in absolute number of circulating red blood cells as
represented by RBC count, hemoglobin concentration, and
hematocrit.
 Hb<-2SD (Age and Sex)
 Anemia is a major cause of morbidity and mortality worldwide.
 In the World Health Organization global database, anemia is
estimated to affect 1.6 billion people.
What is Anemia?

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Approach to
Anemia
 Anemia is not a diagnosis itself.
 Urban 55.9%, Rural 59.4% and Globally 58.4%.
What is Anemia?
Cutoffs for hemoglobin and hematocrit proposed by the WHO to define anemia
Hematocrit (%)Hemoglobin (g/dl)Age groups
<33<11.06 months – 5 years
<34<11.55 – 11 years
<36<12.012 – 13 years
<36<12.0Non pregnant women
<39<13.0Men
Source: WHO 1997

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Approach to
Anemia
What is Anemia?
Hemoglobin and hematocrit in infancy and childhood
Hematocrit (%)Hemoglobin (g/dl)
-2SDMean-2SDMeanAge
425113.516.5Birth (Cord blood)
455614.518.51 – 3 days (capillary)
425413.517.51 Week
395112.516.52 Weeks
314310.514.01 Month
28359.011.52 Months
29359.511.53 – 6 Months
333610.511.50.5 – 2 Years
343711.512.02 – 6 Years
354011.512.56 – 12 Years
364112.014.0Girls 12 – 18 Years
374313.014.5Boys 12 – 18 Years
Values two standard deviations below the mean (-2SD) indicate the lower limit of normal

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Approach to
Anemia
 Mild Anemia (9.5 – 11 g/dl) Asymptomatic, escapes
detection.
 Moderate Anemia (6 – 9.5 g/dl) timely management
to prevent long-term complications.
 Severe Anemia (<6g/dl) prompt management
Nature of Anemia

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Approach to
Anemia
 Decreased production of erythrocytes
-e.g. Iron deficiency, lead poisoning etc.
 Increased destruction of erythrocytes
-e.g. Erythrocyte membrane defects,
Hemoglobinpathies etc.
 Blood Loss
 -e.g. Acute and/or Chronic
Causes of Anemia

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Approach to
Anemia
Clinical Features
Pallor Failure to thrive Flow murmur Orthostatic
Tachycardia Hypotension Tachypnea Unresponsiveness

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Approach to
Anemia
Clinical Features
Decreased
energy
Fatigue Poor
appetite
Headaches Dizziness
Palpitations Shortness
of breath
Lethargy Unconsciousness

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Approach to
Anemia
 One can approach the problem of ANEMIA from three
angles i.e. based on:
1- Pathogenesis
2- Clinical presentation
3- Red cell morphology and indices
Classification of Anemia

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Approach to
Anemia
Pathogenic mechanisms:
1. Inadequate production
2. Excessive destruction (hemolysis)
3. Blood loss (bleeding)
Classification based on Pathogenesis
 Hypo-regenerative: Here blood production is decreased.
-lack of nutrients (iron, vitamin B12 or folic acid)
- defective marrow function or marrow infiltration
 Regenerative: Here marrow is normal and it responds
appropriately to anemia by increasing production of erythrocytes.

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Approach to
Anemia
Classification based on Clinical Presentation
 Acute (bleeding or hemolysis)
 Chronic (primary marrow disorders and various chronic diseases)

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Approach to
Anemia
Based on red cell morphology and indices
 In practice, chiefly mean corpuscular volume (MCV) is very useful.
1- Microcytic (MCV < 80 fl)
2- Normocytic (MCV : 80 – 100 fl)
3- Macrocytic (MCV > 100 fl)

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Approach to
Anemia
Diagnostic Approach to a patient with
suspected Anemia
 Is the patient anemic? If so
 What is the cause of anemia? and
 What is the type of anemia?

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Approach to
Anemia
Clinical approach to an anemic child
 History taking
 Physical examination
 Laboratory investigation

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Approach to
Anemia
History taking
 Any bleeding? Acute or chronic
 Evidence of hemolysis, urine color? if so acute or chronic?
 Age, sex, family history and history of transfusion
 Community and dietary history
 Iron, folate or vitamin B12 deficient
 Medication?
 Infections

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Approach to
Anemia
Physical examination
 Vital signs, Tachycardia, hypotension, fever
 Pallor
 Jaundice
 Lymphadenopathy, hepatosplenomegaly, and bone
tenderness
 Petechia, ecchymosis, and other signs of bleeding disorder
 Signs of nutritional deficiency

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Approach to
Anemia
Laboratory Investigation
 Complete blood count
 Peripheral blood smear
 Reticulocyte count
 Iron supply studies
 Marrow examination
Relative Anemia (CBC limitation)
Increased plasma volume
Pregnancy, HF, Athletes and post
flight astronauts.
Decreased plasma volume
Dehydration and burn

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Approach to
Anemia
Complete blood count
 Red cell parameters
 Absolute reticulocyte count
 WBC count and differential
 Platelet count

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Approach to
Anemia
Red cell parameters
 Direct measurement
- Erythrocyte concentration (RBC) x106/L
- Mean corpuscular volume (MCV) fl
- Hemoglobin g/dl

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Approach to
Anemia
Red cell parameters
 Indirect measurement
- Hematocrit (HCT) = RBC x MCV/10 %
- Mean corpuscular hemoglobin(MCH) = Hbx10/RBC pg
- Mean corpuscular hemoglobin conc.(MCHC)= Hb/Hctx100 g/dl
- Red cell distribution width (RDW) %

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Approach to
Anemia
RBC indices normal value
 MCV 80 – 100 fl
 MCH> 27 pg
 MCHC 32 – 36 g/dl
 RDW 11.5 – 14.5 %

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Approach to
Anemia
Hemoglobin concentration
 Erythrocytes contains a mixture of hemoglobin,
oxyhemoglobin, carboxyhemoglobin, methemoglobin, and
minor amounts of other forms of hemoglobin.
 Low Hb level Iron deficiency, Hemoglobinopathies,
pernicious anemia, hypothyroidism, hemorrhage,
hemolytic anemia, Hodgkin’s disease, leukemia.

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Approach to
Anemia
Hematocrit
 The word hematocrit, also called packed cell volume(PCV)
which means “to separate blood”.
 Increased Hct values are observed in erythrocytosis,
polycythemia vera, and shock.
 Severe dehydration from any cause falsely increase the
Hct value.

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Approach to
Anemia
Hematocrit
 Low Hct values are an indicator of ANEMIA.
 Hct ≤ 30% means that the patient is severely anemic.
 Decrease values also occur in leukemias, lymphomas,
Hodgkin’s disease, adrenal insufficiency, chronic diseases,
acute and chronic blood loss, and hemolytic reactions
(transfusions, chemical, drug reactions, etc.)

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Approach to
Anemia
Mean corpuscular volume (MCV)
 MCV results are the basis of the classification system used
to evaluate an anemia.
 Increased reticulocytes and marked leukocytosis can also
increase MCV.
 The mixed population of microcytes and macrocytes
results in normal MCV values. (Interfering factors)

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Approach to
Anemia
Mean corpuscular volume (MCV)
Cause of microcytic anemia(MCV<80 fl)
Iron deficiency anemia (IDA)
Thalassemia and Hemoglobinopathies
Anemia of chronic disease (ACD)
Sideroblastic anemia
Lead intoxication

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Approach to
Anemia
Mean corpuscular volume (MCV)
Cause of macrocytic anemia(MCV>100 fl)
Anemia with reitculosytosis
Megaloblastic anemia
Drug induced disorder
Alcohol related anemia
Primary marrow disorder
Liver disorders
Spurious macrocytosis

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Approach to
Anemia
Mean corpuscular volume (MCV)
Cause of normocytic anemia(MCV: 80-100 fl)
Dimorphic anemia
Anemia of renal insufficiency
Hemolytic anemia
Anemia of chronic disease (ACD)
Primary marrow disorder

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Approach to
Anemia
Mean corpuscular hemoglobin (MCH)
 The amount of hemoglobin per red blood cell.
 Significant reduction of MCH in patients with iron
deficiency or thalassemia. (Microcytic anemia)
 An increase of MCH is associated with macrocytic anemia.

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Approach to
Anemia
Mean corpuscular hemoglobin (MCH)
 Hyperlipidemia falsely increase MCH. (Interfering factor)
 High heparin concentrations also falsely elevate MCH
value.
 WBC counts > 50,000/mm3 also provide increased level for
MCV as well as for Hb.

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Approach to
Anemia
Mean corpuscular hemoglobin concentration (MCHC)
 Decreased MCHC indicates that packed RBCs contains less
Hb than normal.
 Decreased in iron deficiency, microcytic anemias, chronic
blood loss and some thalassemias.
 MCHC cannot be greater than 37 g/dl.
 Increased MCHC levels (RBCs cannot accommodate more
than 37 g/dl Hb) occur in spherocytosis, in newborns and
infants.

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Approach to
Anemia
Red blood cell distribution width (RDW)
 Increase in the RDW suggest the presence of a mixed
population of cells. Double populations, whether
microcytic cells + normal cells or macrocytic cells mixed
with normal cells.

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Approach to
Anemia
Red blood cell distribution width (RDW)
 Thalassemia (normal RDW)
 Iron deficiency anemia (high RDW)
 Chronic disease anemia (normal RDW)
 Vitamin B12 or folate deficiency (high RDW)
 Immune hemolytic anemia (high RDW)
 Post hemorrhagic anemia (high RDW)
 Marked reitculosytosis (high RDW)

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Approach to
Anemia
Peripheral blood smear
 It can provide important additional information about RBC
morphology.
 Done when the patient’s indices are abnormal.
 Visible changes in cell diameter, shape, and hemoglobin
content can be used to distinguish both microcytic and
macrocytic cells from normocytic RBCs.
 It is not only an indication of RBC abnormalities but also a
diagnosis of diseases.

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Approach to
Anemia
Reticulocyte count (Immature RBCs)
 A reticulocyte count gives an indication of the BM status
-decreased activity
- appropriate response to the anemia.
 A reticulocyte production index (RPI) provides a more
accurate representation of marrow activity.
% reticulocytes × (patient hematocrit/45) ÷ reticulocyte maturation
time (days) in peripheral blood

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Approach to
Anemia
Reticulocyte index
 The RPI for healthy individual = 1.0-2.0%
 RPI< 1% with anemia (Decreased production of reticulocytes)
 RPI > 2% with anemia (Loss of RBC e.g. destruction or bleeding)
Maturation time (days)
Hct≥40% 1 day
Hct: 30 – 40 % 1.5 day
Hct: 20 – 30 % 2 day
Hct < 20 % 2.5 day

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Approach to
Anemia
Reticulocyte index
 High reticulocyte count:
- Hemolysis
- Hemorrhage
- Splenic sequestration
- Sepsis
- Recovery from vitamin or iron deficiency.

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Approach to
Anemia
Reticulocyte index
 Low reticulocyte count:
- Congenital or acquired
- Aplastic / hypoplastic anemia
- Transient erythroblastopenia of childhood
- Pure red cell aplasia
- Bone marrow infiltration

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Approach to
Anemia
Pattern of RBCs in peripheral smear
 Microcytic hypochromic red cells  IDA, ACD, Thalassemia
 Oval macrocytes  Megaloblastic anemia
 Sickled red cells  Sickle cell disorders
 Spherocytes  Hereditary spherocytosis, A. Hemolytic A.
 Target cells  Thalassemia, Liver disease,

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Approach to
Anemia
Pattern of RBCs in peripheral smear
 Schistocytes  Microangiopathic hemolytic anemia
 Burr cells  Uremia
 Tear drop red cells  Myelophthisic anemia, myelofibrosis
 Bite Cells  G6PD deficiency

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Approach to
Anemia

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Approach to
Anemia

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Approach to
Anemia

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Approach to
Anemia

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Approach to
Anemia
Indications for RBC transfusion in children
 Infants
-Hematocrit<20 and asymptomatic with reti c< 100000/cu mm
-Hematocrit<30 and requiring oxygen
-Hematocrit<35 and mechanical ventilation;
H.R> 180/min or R.R> 80/min persisting for >24 hours;
weight gain< (10g/day) over 4 days while on >100Cal/kg/d

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Approach to
Anemia
Indications for RBC transfusion in children
 Children
 Hb ≤ 4 g/dl, Hct ≤ 12, irrespective of clinical condition
 Hb 4 – 6 g/dl, Hct 13 – 18, hypoxia, acidosis, dyspenea or
impaired consciousness
 Malaria with hyperparaseitemia > 20%
 Features of cardiac decompensation

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Approach to
Anemia
Conclusion
 Anemia is not a diagnosis itself.
 Initial approach to the diagnosis
- Perform complete history and physical examination.
- Review of the CBC with reticulocyte count
- Examination of peripheral smear
 There maybe more than one cause of ANEMIA.

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Approach to
Anemia
Reference
 Nelson
 Ghai
 Principles of Anemia evaluation 1st edition
- Bridges KP and Howard
 Lecturio
 Oxford handbook of Clinical Hematology
- Oxford University press UK, 2009.

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Approach to
Anemia