Diagnostic Approach to Anemia Prof. Dr. Teoman SOYSAL Definition of anemia Anemia: A reduction in – red cell mass – O2-carrying capacity of blood It is expressed.
Download ReportTranscript Diagnostic Approach to Anemia Prof. Dr. Teoman SOYSAL Definition of anemia Anemia: A reduction in – red cell mass – O2-carrying capacity of blood It is expressed.
Slide 1
Diagnostic Approach to
Anemia
Prof. Dr. Teoman SOYSAL
Slide 2
Definition of anemia
Anemia: A reduction in
– red cell mass
–
O2-carrying capacity of blood
It is expressed in terms of reduction
in the concentration of Hb (or RBC or
Hct%) compared to values obtained
from a reference population.
(2 SD below normal)
Slide 3
Reference values (adults) (I)
Parameter
Female
Male
RBC (x1012/L) 4.8+0.6 5.4+0.9
Hb (g/dL)
14+2
16+2
Htc (%)
42+5
47+5
Slide 4
Definition of anemia
Hb level of a patient which is below the normal
ranges of that age and sex.
For adults:
WHO criteria define anemia as
– hemoglobin
But:
<12 g/dL in women and
<13 g/dL in men
The reference values for red cells ,Hb or Hct may difer
according to
–
–
–
–
–
sex/age
Race
Altitude
Socioeconomical changes
Study/reference etc
Slide 5
BEUTLER andWAALEN BLOOD, 1 MARCH 2006 VOLUME 107, NUMBER 5
Slide 6
Age and blood count changes
Neutrophyls
Eos.
Baso
Lenfo
Mono
Hb
12 mo 6-17.5
1.5-8.5
0.05-0.7
0-0.20
4-10.5
0.05-1.1
11.1-14.1
4y
5.5-15
1.5-8.5
0.020.65
0-0.20
2-8
0-0.8
11.2-14.3
6y
5-14.5
1.5-8
0-0.65
0-0.20
1.5-7
0-0.8
11.4-14.5
10 y
4.5-13
1.8-8
0-0.60
0-0.20
1.5-6.5
0-0.8
11.8-15
21 y
4.5-11
1.8-7.7
0-0.45
0-0.20
1-4.8
0-0.8
E: 16
K: 14
age
WBC
WBC: x10E3/mm3 Hb:g/dL
Slide 7
Reference values (II)
Ret (% / n)
0.5-2.5 / 50-100x109/L
MCV (fl)
90+7
MCH (pg)
29+2
MCHc (g/dL)
34+2
RDW (%)
11.5-14.5
Slide 8
RBC
%
50
100
200
fl
Slide 9
RBC
RDW: Red cell distribution width
%
50
100
200
fl
Slide 10
RBC
%
50
100
200
fl
Slide 11
Reticulocyte
Normal Ranges
Male: % 0.8 - 2.5
Female: % 0.8 - 4.1
Increased counts
•Hemolysis
•Acute bleeding
•Response to treatment
Corrected Rtc: Patient Hb/Normal Hb x Rtc %
Reticulocytosis: > 100.000 /mm3
Slide 12
Diagnosis and investigation:
Is the patient anemic?
What is the type of anemia?
What is the cause of anemia?
Slide 13
Classification of anemia
Morphologic
– Normocytic: MCV= 80-100fL
– Macrocytic: MCV > 100 fL
– Microcytic : MCV < 80 fL
Pathogenic (underlying mechanism)
– Blood loss (bleeding)
– Decreased RBC production
– Increased RBC destruction/pooling
Slide 14
!!!!!
Plasma volume changes have to be
considered before determining a diagnosis
of anemia .
– Volume contraction:Underestimation of anemia
– Volume overload: Underestimation of Hb level
Slide 15
Volume changes/acute bleeding
and anemia
1
normal
Hct:Normal
2
Increased
plasma
volume
Hct: Low
3
Dehydration
Hct:Increased
4
5
Acute blood
loss(early)
Hct:unchanged
Chronic
anemia
Hct: Low
Slide 16
!!!!!
A normal Hb in a patient in whom an
elevated Hb level is expected may
represent anemia .(eg:COPD + Hb:N)
Slide 17
!!!!!!
Different red cell measures of a patient may
give discordant values in special conditions.
eg:Thalassemia trait
Low Hb, high RBC, low MCV,normal RDW
Hb: 10 g/dL (anemia)
RBC: 6.5 million/mm3 (erythrocytosis)
MVC : 65 fL
RDW: Normal
Slide 18
!!!!
Anemia is rarely a disease by itself,
It is mostly a manifestation or
consequence of an underlying
(genetic or acquired) disease.
The finding of anemia has to start
attempts to disclose an underlying
disease .
– What is the cause of anemia ?
Slide 19
Normocytic Anemias
Acute posthemorrhagic anemia
Hemolytic anemia
(except thalassemia
and some other Hb
disorders)
Aplastic anemia
Pure red cell aplasia
Bone marrow
infiltration
Endocrin diseases
Renal failure
Liver disease
Chronic disease anemia
Protein malnutrition
Hypovitaminosis C
Slide 20
Microcytic anemias
Iron deficiency anemia
Thalassemia
Sideroblastic anemia
Lead poisoning
Anemia of chronic diseases
(some cases)
Slide 21
Macrocytic anemias
Megaloblastic
– Oval macrocytes
Non-megaloblastic
Slide 22
Megaloblastic Macrocytic
Anemias
Vit B12 deficiency
Folic acid deficiency
Other.
Slide 23
Non-megaloblastic
Macrocytic Anemias
Anemia of acute
bleeding
Hemolytic anemias
Leukemias
(esp: acute)
Myelodysplastic
syndromes
Liver disease
Aplastic anemia
Diseases infiltrative
to the bone
marrow
Alcoholism
Hypothyroidism
Scurvy
Slide 24
Pathogenic classification
(Causes of anemia)
Relative (increased plasma volume)
Decreased RBC production
Blood loss
– Anemia due to acute bleeding
Increased RBC destruction
Slide 25
Pathogenic classification
(Causes of anemia)
Decreased RBC production
– Decreased Hb production
– Defective DNA synthesis
– Stem cell defects
Pluripotent stem cell
Erythroid stem cell(progenitors)
– Other less defined reasons
Blood loss
– Anemia due to acute bleeding
Increased RBC destruction
Relative(increased plasma volume)
Slide 26
Decreased Hb production
Iron deficiency anemia
Thalassemia
Sideroblastic anemia
Lead poisoning
Slide 27
Defective DNA synthesis
Vit B12 deficiency
Folic acid deficiency
Other.
Slide 28
Pluripotent stem cell defects
Aplastic anemia
Leukemia or myelodysplastic syndromes
Defective erythroid stem cell
Pure red cell aplasia
Anemia of chronic renal failure
Endocrin disease anemia
Congenital dyserythropoetic anemias
Slide 29
Decreased RBC production due to
multipl or undefined mechanisms
Anemia of chronic diseases
Bone marrow infiltration
Anemia due to nutritional defects
Slide 30
Anemias caused by
increased RBC destruction
(hemolytic anemias)
Can be classified as;
Hemolysis due to intracorpuscular defects
Hemolysis due to extracorpuscular defects
Or
Hereditary hemolytic diseases
Acquired hem. diseases
Or
Intravascular hemolysis
Extravascular hemolysis etc.
Slide 31
A Very Simple Classification of Hemolytic Anemias
1- Abnormalities of RBC interior
a. Enzyme defects
b. Hemoglobinopathies & Thalassemia M
Hereditary
2-RBC membrane abnormalities
a. Hereditary spherocytosis, elliptocytosis etc
b. Paroxysmal nocturnal hemoglobinuria
c. Spur cell anemia
3- Extrinsic factors
a. Hypersplenism
b. Antibody : immune hemolysis
c. Traumatic & Microangiopathic hemolysis
d. Infections , toxins , etc
Acquired
Slide 32
Is the patient anemic ?
RBC count
HB level
Hct level
Volume status
Slide 33
What is the type of
anemia?
History and physical exam.
RBC,HB,Hct ,
MCV, MCH,RDW
Red cell morphology ( peripheral smear)
Reticulocyte count
– Incresed ?
Other Lab. investigations
Slide 34
Lab. investigation of anemia(1)
WBC count and differential
Platelet count and morphology
ESR
Biochemistry, special tests and others
Bone marrow exam.(only when indicated)
Slide 35
Lab. investigation of anemia(2)
Serum values of
– Iron
– TIBC
– Ferritin
– Bilirubins
– Proteins / electrophoresis
– LDH
– Vit B12 and /or Folic acid
(None of these tests are routine screening tests)
Slide 36
Lab. Investigation of Anemia(3)
Liver, renal, endocrin functional tests
Urinalysis
– Hemosiderin
Occult GIS bleeding / parasites etc
(tests should be chosen individually-do not order routinly )
Tests to diagnose the type of hemolytic anemia
– If hemolytic anemia is considered
Slide 37
Normocytic
anemia
Retic. count
normal/low
Secondary anemia
Renal, Hepatic,
Endocrin , Chronic
disease
Retic. count
increased
• No sign of secondary anemia
• Other signs of bone marrow
disease may be +
Response to
treatment
Hemolytic
anemia
(Normal marrow)
Hypoplastic
Marrow
AA, pure red
cell aplasia
Bone marrow
infiltrative diseases
Leukemia ,
Myelofibrosis
Metastatic disease
Dysplastic
marrow: MDS
Acute
bleeding
Slide 38
Microcytic
anemia
Serum iron
high
Serum iron
normal /high
Serum iron
decreased
Bone marrow iron
content and
sideroblasts
Hemoglobin
studies
Ferritin low
Ferritin:
Normal or
increased
Sideroblastic
anemia
Thalassemia , HbC
, others
Iron
deficiency
Anemia of
chronic
diseases
Slide 39
Macrocytic anemia
Peripheral smear
Retic. count
Retic. count
Normal/ decreased
Retic. count
Increased
Hemolysis
Megaloblastic
Acute
bleeding
Deficiencies of
VitB12 ,Folic acid
or other causes
Non-Megaloblastic
Liver diseases
Myelodysplastic syndrome
Bone marrow infiltration
Acute leukemia
Aplastic Anemia,
Alcoholism
Hypothyoidism etc
Slide 40
Case I
38 years old, ♀
Tiredness, hair loss, nail changes
Slide 41
Microcytic
anemia
Serum iron
high
Serum iron
normal /high
Serum iron
decreased
Bone marrow iron
content and
sideroblasts
Hemoglobin
studies
Ferritin low
Ferritin:
Normal or
increased
Sideroblastic
anemia
Thalassemia , HbC
, others
Iron
deficiency
Anemia of
chronic
diseases
Slide 42
Microcytic anemias
Diagnosis
(type of
anemia)
MCV
RDW
Serum
Iron
Iron
binding
capacity
Iron
deficiency
Thalassemia
Chronic
disease
anemia
N
N
RBC count:
Thalassemia minor >Iron deficiency
N
Ferritin
ESR/acute
phase
signs
Hemogl.
changes
May
change
None
Normal
May be
diagnostic
Elevated
None
Slide 43
Case I
38 years old, ♀
Tiredness, hair loss, nail changes
Slide 44
What is your diagnosis?
What is the next step?
– Prove iron deficiency
Serum iron, TIBC, Ferritin
– Find out the cause of iron deficiency
Chronic blood loss / excessive need-inadequate
intake
– Menstruel bleeding, Pregnancy
– GI bleeding
– Inadequate intake or malabsorbtion etc
– Treat both iron deficiency and the cause
Slide 45
Case II
26 y o
Slight symptoms
•Decreased excercise
tolerence
•Paleness
•Long history of being
anemic on routine
CBC’s ,non responsive
to iron
RBC:5.500.000/mm3
Hb: 10 g/dL
MCV: 60 fL
RDW: 14.3
Retic: %2
WBC: 5000/mm3
Plt: 200.000/mm3
Name the blood picture.
Further questions to ask to the patient?
Further tests to do ?
Ferritin : slightly elevated
HbA2: slightly elevated, Hb F: normal
Final Diagnosis ?
Slide 46
Case III
• 70 y o, male
•Fatigue, weakness
•Sore tongue, poor taste
sensation
•Papill. atrophy-beefy tongue
•Paresthesias
•Loss of position sense, ataxia
•Decreased deepWBC:
tendon
reflexes
Hgb:
2.300/µl
11 g/dL
3 units of red cellHct:
transfusion
%33
made before admission
MCV: 122 fL
MCH: 39pg
MCHC: %34
RDW: 30.5
Plt: 100.000/µl
Retic: 1%
Macrocytosis
Anisocytosis,
neutrophyl
hypersegmentation,
oval macrocytes
Slide 47
Macrocytic anemia
Peripheral smear
Retic. count
Retic. count
Normal/ decreased
Retic. count
Increased
Hemolysis
Acute bleeding
Megaloblastic
Deficiencies of
VitB12 ,Folic acid
or other causes
Non-Megaloblastic
Liver diseases
Myelodysplastic syndrome
Bone marrow infiltration
Acute leukemia
Aplastic Anemia,
Alcoholism
Hypothyoidism etc
Slide 48
What is the blood picture ?
(The type of the disorder)
What is your diagnosis?
– Why?
Slide 49
Normocytic
anemia
Retic. count
normal/low
Secondary anemia
Renal, Hepatic,
Endocrin , Chronic
disease
Retic. count
increased
• No sign of secondary anemia
• Other signs of bone marrow
disease may be +
Response to
treatment
Hemolytic
anemia
(Normal marrow)
Hypoplastic
Marrow
AA, pure red
cell aplasia
Bone marrow
infiltrative diseases
Leukemia ,
Myelofibrosis
Metastatic disease
Dysplastic
marrow: MDS
Acute
bleeding
Slide 50
60 y o
Normocytic anemia
Reticulocytes: 1%
Pale, pruritus,
hypertension
Urea + creatinin
elevated
?
Hoarse voice
Lethargy
Hair loss
Dry skin
Weight gain
Poor memory
Bradycardia
?
Symmetric polyarthritis
Morning stiffness
Sc nodules
?
Slide 51
Case IV
• 65 y o , male
•One month history of fever, cough and hemoptysis
• ESR: 80mm/h; high CRP
•Sputum + for TBC bacteria; chest x-ray shows right apical infiltrate
Normocytic anemia, MCV normal,
RDW ↑,
What is the type of anemia?
What is the diagnosis?
•This case could also present as a
microcytic anemia .What would you
expect from the iron studies in that
Retic.: 2%
situation?
Low iron, Low TIBC, High Ferritin
Slide 52
Normocytic
anemia
Retic. count
normal/low
Secondary anemia
Renal, Hepatic,
Endocrin , Chronic
disease
Retic. count
increased
• No sign of secondary anemia
• Other signs of bone marrow
disease
Response to
treatment
Hemolytic
anemia
Acute
bleeding
(Normal marrow)
Hypoplastic
Marrow
AA, pure red
cell aplasia
Bone marrow
infiltrative diseases
Leukemia ,
Myelofibrosis
Metastatic disease
How to decide
the next step?
Dysplastic
marrow: MDS
History
PE
Smear
Other tests
Slide 53
Case IX
67 y o, male
•Anemia symptoms
•Severe bone pain
CBC
•Normocytic anemia
What is your possible diagnosis?
What is the next step?
•ESR:>100mm/h
•Hypercalcemia
•Hyperglobulinemia
•Renal failure
Slide 54
Morphologic abnormalities in hemolytic anemias
• Sickle cell:
Sickle cell anemia
• Target cels:
Thalassemia, HbC disease, liver disease,
splenectomy
• Schistocytes:
Microangiopathic hem anemia, uremia, DIC,
malignant hypertesion, eclampsia,
disseminated vasculitis or malignancy,
• Agglutination:
Cold agglutinin disease
• Heinz bodies:
Unstable Hb, G6PD deficiency and oxidant stress
Slide 55
Special Lab. Examinations
Coombs antiglobulin test - immune hemolysis
Osmotic fragility test - spherocytosis
Autohemolysis- G6PD,PK, spherocytosis
Red cell enzyme assays- RBC enzyme defects
Membrane protein analysis- membrane defects
Red cell sickling, HbS- sickle cell anemia
Hemoglobin electrophoresis and HbA2, Hb F , HHb,etc -
Hemoglobinopathies and thalassemias
HAM and sucrose lysis tests and GPI-linked protein
analysis by flow cytometry- PNH
Oxygen dissociation curve- High oxygen affinity Hb
Slide 56
Case V
18 y o , male
Weakness, paleness, slight
icterus, splenomegaly, bile stones
Family history +
WBC: 5600/µl
Hgb: 9,6 g/dL
MCHC: %37
Plt: 300.000/µl
Retic: %9
?
Ind Bil: slightly elevated
LDH: elevated
Haptoglobin : low
Red cell osmotic fragility increased
Normal RBC
spherocyte
?
Slide 57
Case VI
38 y o
Cough , fever
WBC: 12.000/µl
Hgb: 11 g/dL
Hct: 22 %
MCV: 130
MCH: 40
MCHC: 36
RDW:28
Plt: 160.000/µl
Slide 58
Slide 59
Case VII
34 y o, male
2-3 weeks history of
•Decreased exercise capacity
•Paleness
•Headache, sore throat
2 days history of
•Cough and fever
•Red spots on the skin
CBC
WBC: 33.000/mm3
Hb: 7 g/dL
Retic: 1%
Plt: 12.000/mm3
Slide 60
Case IX
60 y o, female
Sudden onset
Pallor, palpitation
Slight scleral icterus
splenomegaly
CBC
Hb: 8 g/dL
WBC: 10.000/mm3
Plt: 450.000/mm3
Retic: 10%
What is your diagnosis?
What is your next step?
Indirect bilirubin: high
LDH: high
Haptoglobin: low
D/I: Coombs +
Slide 61
Case X
70 y o , male
•Under examination for
prostat enlargement
+One month history of
•Bone pain
•Symptoms of anemia
WBC: 8000/mm3
Hb: 8 g/dL
MCV: 88 fL
RDW: 14
Retic: 2%
Plt: 220.000/mm3
Slide 62
Morphologic abnormalities in hemolytic anemias
Polychromasia: Reticulocytes
Spherocyte :
Hereditary spherocytosis, immune hem. anemia,
burns, chemical injury to RBC
Elliptocytes:
Hereditary ovalocytosis,
Stomatocytes: Hereditary stomatocytosis, alcoholism
Acanthocytes: Spur cell anemia with liver disease,
abetalipoproteinemia
Echinocytes:
Pyruvate kinase deficiency, uremia
Diagnostic Approach to
Anemia
Prof. Dr. Teoman SOYSAL
Slide 2
Definition of anemia
Anemia: A reduction in
– red cell mass
–
O2-carrying capacity of blood
It is expressed in terms of reduction
in the concentration of Hb (or RBC or
Hct%) compared to values obtained
from a reference population.
(2 SD below normal)
Slide 3
Reference values (adults) (I)
Parameter
Female
Male
RBC (x1012/L) 4.8+0.6 5.4+0.9
Hb (g/dL)
14+2
16+2
Htc (%)
42+5
47+5
Slide 4
Definition of anemia
Hb level of a patient which is below the normal
ranges of that age and sex.
For adults:
WHO criteria define anemia as
– hemoglobin
But:
<12 g/dL in women and
<13 g/dL in men
The reference values for red cells ,Hb or Hct may difer
according to
–
–
–
–
–
sex/age
Race
Altitude
Socioeconomical changes
Study/reference etc
Slide 5
BEUTLER andWAALEN BLOOD, 1 MARCH 2006 VOLUME 107, NUMBER 5
Slide 6
Age and blood count changes
Neutrophyls
Eos.
Baso
Lenfo
Mono
Hb
12 mo 6-17.5
1.5-8.5
0.05-0.7
0-0.20
4-10.5
0.05-1.1
11.1-14.1
4y
5.5-15
1.5-8.5
0.020.65
0-0.20
2-8
0-0.8
11.2-14.3
6y
5-14.5
1.5-8
0-0.65
0-0.20
1.5-7
0-0.8
11.4-14.5
10 y
4.5-13
1.8-8
0-0.60
0-0.20
1.5-6.5
0-0.8
11.8-15
21 y
4.5-11
1.8-7.7
0-0.45
0-0.20
1-4.8
0-0.8
E: 16
K: 14
age
WBC
WBC: x10E3/mm3 Hb:g/dL
Slide 7
Reference values (II)
Ret (% / n)
0.5-2.5 / 50-100x109/L
MCV (fl)
90+7
MCH (pg)
29+2
MCHc (g/dL)
34+2
RDW (%)
11.5-14.5
Slide 8
RBC
%
50
100
200
fl
Slide 9
RBC
RDW: Red cell distribution width
%
50
100
200
fl
Slide 10
RBC
%
50
100
200
fl
Slide 11
Reticulocyte
Normal Ranges
Male: % 0.8 - 2.5
Female: % 0.8 - 4.1
Increased counts
•Hemolysis
•Acute bleeding
•Response to treatment
Corrected Rtc: Patient Hb/Normal Hb x Rtc %
Reticulocytosis: > 100.000 /mm3
Slide 12
Diagnosis and investigation:
Is the patient anemic?
What is the type of anemia?
What is the cause of anemia?
Slide 13
Classification of anemia
Morphologic
– Normocytic: MCV= 80-100fL
– Macrocytic: MCV > 100 fL
– Microcytic : MCV < 80 fL
Pathogenic (underlying mechanism)
– Blood loss (bleeding)
– Decreased RBC production
– Increased RBC destruction/pooling
Slide 14
!!!!!
Plasma volume changes have to be
considered before determining a diagnosis
of anemia .
– Volume contraction:Underestimation of anemia
– Volume overload: Underestimation of Hb level
Slide 15
Volume changes/acute bleeding
and anemia
1
normal
Hct:Normal
2
Increased
plasma
volume
Hct: Low
3
Dehydration
Hct:Increased
4
5
Acute blood
loss(early)
Hct:unchanged
Chronic
anemia
Hct: Low
Slide 16
!!!!!
A normal Hb in a patient in whom an
elevated Hb level is expected may
represent anemia .(eg:COPD + Hb:N)
Slide 17
!!!!!!
Different red cell measures of a patient may
give discordant values in special conditions.
eg:Thalassemia trait
Low Hb, high RBC, low MCV,normal RDW
Hb: 10 g/dL (anemia)
RBC: 6.5 million/mm3 (erythrocytosis)
MVC : 65 fL
RDW: Normal
Slide 18
!!!!
Anemia is rarely a disease by itself,
It is mostly a manifestation or
consequence of an underlying
(genetic or acquired) disease.
The finding of anemia has to start
attempts to disclose an underlying
disease .
– What is the cause of anemia ?
Slide 19
Normocytic Anemias
Acute posthemorrhagic anemia
Hemolytic anemia
(except thalassemia
and some other Hb
disorders)
Aplastic anemia
Pure red cell aplasia
Bone marrow
infiltration
Endocrin diseases
Renal failure
Liver disease
Chronic disease anemia
Protein malnutrition
Hypovitaminosis C
Slide 20
Microcytic anemias
Iron deficiency anemia
Thalassemia
Sideroblastic anemia
Lead poisoning
Anemia of chronic diseases
(some cases)
Slide 21
Macrocytic anemias
Megaloblastic
– Oval macrocytes
Non-megaloblastic
Slide 22
Megaloblastic Macrocytic
Anemias
Vit B12 deficiency
Folic acid deficiency
Other.
Slide 23
Non-megaloblastic
Macrocytic Anemias
Anemia of acute
bleeding
Hemolytic anemias
Leukemias
(esp: acute)
Myelodysplastic
syndromes
Liver disease
Aplastic anemia
Diseases infiltrative
to the bone
marrow
Alcoholism
Hypothyroidism
Scurvy
Slide 24
Pathogenic classification
(Causes of anemia)
Relative (increased plasma volume)
Decreased RBC production
Blood loss
– Anemia due to acute bleeding
Increased RBC destruction
Slide 25
Pathogenic classification
(Causes of anemia)
Decreased RBC production
– Decreased Hb production
– Defective DNA synthesis
– Stem cell defects
Pluripotent stem cell
Erythroid stem cell(progenitors)
– Other less defined reasons
Blood loss
– Anemia due to acute bleeding
Increased RBC destruction
Relative(increased plasma volume)
Slide 26
Decreased Hb production
Iron deficiency anemia
Thalassemia
Sideroblastic anemia
Lead poisoning
Slide 27
Defective DNA synthesis
Vit B12 deficiency
Folic acid deficiency
Other.
Slide 28
Pluripotent stem cell defects
Aplastic anemia
Leukemia or myelodysplastic syndromes
Defective erythroid stem cell
Pure red cell aplasia
Anemia of chronic renal failure
Endocrin disease anemia
Congenital dyserythropoetic anemias
Slide 29
Decreased RBC production due to
multipl or undefined mechanisms
Anemia of chronic diseases
Bone marrow infiltration
Anemia due to nutritional defects
Slide 30
Anemias caused by
increased RBC destruction
(hemolytic anemias)
Can be classified as;
Hemolysis due to intracorpuscular defects
Hemolysis due to extracorpuscular defects
Or
Hereditary hemolytic diseases
Acquired hem. diseases
Or
Intravascular hemolysis
Extravascular hemolysis etc.
Slide 31
A Very Simple Classification of Hemolytic Anemias
1- Abnormalities of RBC interior
a. Enzyme defects
b. Hemoglobinopathies & Thalassemia M
Hereditary
2-RBC membrane abnormalities
a. Hereditary spherocytosis, elliptocytosis etc
b. Paroxysmal nocturnal hemoglobinuria
c. Spur cell anemia
3- Extrinsic factors
a. Hypersplenism
b. Antibody : immune hemolysis
c. Traumatic & Microangiopathic hemolysis
d. Infections , toxins , etc
Acquired
Slide 32
Is the patient anemic ?
RBC count
HB level
Hct level
Volume status
Slide 33
What is the type of
anemia?
History and physical exam.
RBC,HB,Hct ,
MCV, MCH,RDW
Red cell morphology ( peripheral smear)
Reticulocyte count
– Incresed ?
Other Lab. investigations
Slide 34
Lab. investigation of anemia(1)
WBC count and differential
Platelet count and morphology
ESR
Biochemistry, special tests and others
Bone marrow exam.(only when indicated)
Slide 35
Lab. investigation of anemia(2)
Serum values of
– Iron
– TIBC
– Ferritin
– Bilirubins
– Proteins / electrophoresis
– LDH
– Vit B12 and /or Folic acid
(None of these tests are routine screening tests)
Slide 36
Lab. Investigation of Anemia(3)
Liver, renal, endocrin functional tests
Urinalysis
– Hemosiderin
Occult GIS bleeding / parasites etc
(tests should be chosen individually-do not order routinly )
Tests to diagnose the type of hemolytic anemia
– If hemolytic anemia is considered
Slide 37
Normocytic
anemia
Retic. count
normal/low
Secondary anemia
Renal, Hepatic,
Endocrin , Chronic
disease
Retic. count
increased
• No sign of secondary anemia
• Other signs of bone marrow
disease may be +
Response to
treatment
Hemolytic
anemia
(Normal marrow)
Hypoplastic
Marrow
AA, pure red
cell aplasia
Bone marrow
infiltrative diseases
Leukemia ,
Myelofibrosis
Metastatic disease
Dysplastic
marrow: MDS
Acute
bleeding
Slide 38
Microcytic
anemia
Serum iron
high
Serum iron
normal /high
Serum iron
decreased
Bone marrow iron
content and
sideroblasts
Hemoglobin
studies
Ferritin low
Ferritin:
Normal or
increased
Sideroblastic
anemia
Thalassemia , HbC
, others
Iron
deficiency
Anemia of
chronic
diseases
Slide 39
Macrocytic anemia
Peripheral smear
Retic. count
Retic. count
Normal/ decreased
Retic. count
Increased
Hemolysis
Megaloblastic
Acute
bleeding
Deficiencies of
VitB12 ,Folic acid
or other causes
Non-Megaloblastic
Liver diseases
Myelodysplastic syndrome
Bone marrow infiltration
Acute leukemia
Aplastic Anemia,
Alcoholism
Hypothyoidism etc
Slide 40
Case I
38 years old, ♀
Tiredness, hair loss, nail changes
Slide 41
Microcytic
anemia
Serum iron
high
Serum iron
normal /high
Serum iron
decreased
Bone marrow iron
content and
sideroblasts
Hemoglobin
studies
Ferritin low
Ferritin:
Normal or
increased
Sideroblastic
anemia
Thalassemia , HbC
, others
Iron
deficiency
Anemia of
chronic
diseases
Slide 42
Microcytic anemias
Diagnosis
(type of
anemia)
MCV
RDW
Serum
Iron
Iron
binding
capacity
Iron
deficiency
Thalassemia
Chronic
disease
anemia
N
N
RBC count:
Thalassemia minor >Iron deficiency
N
Ferritin
ESR/acute
phase
signs
Hemogl.
changes
May
change
None
Normal
May be
diagnostic
Elevated
None
Slide 43
Case I
38 years old, ♀
Tiredness, hair loss, nail changes
Slide 44
What is your diagnosis?
What is the next step?
– Prove iron deficiency
Serum iron, TIBC, Ferritin
– Find out the cause of iron deficiency
Chronic blood loss / excessive need-inadequate
intake
– Menstruel bleeding, Pregnancy
– GI bleeding
– Inadequate intake or malabsorbtion etc
– Treat both iron deficiency and the cause
Slide 45
Case II
26 y o
Slight symptoms
•Decreased excercise
tolerence
•Paleness
•Long history of being
anemic on routine
CBC’s ,non responsive
to iron
RBC:5.500.000/mm3
Hb: 10 g/dL
MCV: 60 fL
RDW: 14.3
Retic: %2
WBC: 5000/mm3
Plt: 200.000/mm3
Name the blood picture.
Further questions to ask to the patient?
Further tests to do ?
Ferritin : slightly elevated
HbA2: slightly elevated, Hb F: normal
Final Diagnosis ?
Slide 46
Case III
• 70 y o, male
•Fatigue, weakness
•Sore tongue, poor taste
sensation
•Papill. atrophy-beefy tongue
•Paresthesias
•Loss of position sense, ataxia
•Decreased deepWBC:
tendon
reflexes
Hgb:
2.300/µl
11 g/dL
3 units of red cellHct:
transfusion
%33
made before admission
MCV: 122 fL
MCH: 39pg
MCHC: %34
RDW: 30.5
Plt: 100.000/µl
Retic: 1%
Macrocytosis
Anisocytosis,
neutrophyl
hypersegmentation,
oval macrocytes
Slide 47
Macrocytic anemia
Peripheral smear
Retic. count
Retic. count
Normal/ decreased
Retic. count
Increased
Hemolysis
Acute bleeding
Megaloblastic
Deficiencies of
VitB12 ,Folic acid
or other causes
Non-Megaloblastic
Liver diseases
Myelodysplastic syndrome
Bone marrow infiltration
Acute leukemia
Aplastic Anemia,
Alcoholism
Hypothyoidism etc
Slide 48
What is the blood picture ?
(The type of the disorder)
What is your diagnosis?
– Why?
Slide 49
Normocytic
anemia
Retic. count
normal/low
Secondary anemia
Renal, Hepatic,
Endocrin , Chronic
disease
Retic. count
increased
• No sign of secondary anemia
• Other signs of bone marrow
disease may be +
Response to
treatment
Hemolytic
anemia
(Normal marrow)
Hypoplastic
Marrow
AA, pure red
cell aplasia
Bone marrow
infiltrative diseases
Leukemia ,
Myelofibrosis
Metastatic disease
Dysplastic
marrow: MDS
Acute
bleeding
Slide 50
60 y o
Normocytic anemia
Reticulocytes: 1%
Pale, pruritus,
hypertension
Urea + creatinin
elevated
?
Hoarse voice
Lethargy
Hair loss
Dry skin
Weight gain
Poor memory
Bradycardia
?
Symmetric polyarthritis
Morning stiffness
Sc nodules
?
Slide 51
Case IV
• 65 y o , male
•One month history of fever, cough and hemoptysis
• ESR: 80mm/h; high CRP
•Sputum + for TBC bacteria; chest x-ray shows right apical infiltrate
Normocytic anemia, MCV normal,
RDW ↑,
What is the type of anemia?
What is the diagnosis?
•This case could also present as a
microcytic anemia .What would you
expect from the iron studies in that
Retic.: 2%
situation?
Low iron, Low TIBC, High Ferritin
Slide 52
Normocytic
anemia
Retic. count
normal/low
Secondary anemia
Renal, Hepatic,
Endocrin , Chronic
disease
Retic. count
increased
• No sign of secondary anemia
• Other signs of bone marrow
disease
Response to
treatment
Hemolytic
anemia
Acute
bleeding
(Normal marrow)
Hypoplastic
Marrow
AA, pure red
cell aplasia
Bone marrow
infiltrative diseases
Leukemia ,
Myelofibrosis
Metastatic disease
How to decide
the next step?
Dysplastic
marrow: MDS
History
PE
Smear
Other tests
Slide 53
Case IX
67 y o, male
•Anemia symptoms
•Severe bone pain
CBC
•Normocytic anemia
What is your possible diagnosis?
What is the next step?
•ESR:>100mm/h
•Hypercalcemia
•Hyperglobulinemia
•Renal failure
Slide 54
Morphologic abnormalities in hemolytic anemias
• Sickle cell:
Sickle cell anemia
• Target cels:
Thalassemia, HbC disease, liver disease,
splenectomy
• Schistocytes:
Microangiopathic hem anemia, uremia, DIC,
malignant hypertesion, eclampsia,
disseminated vasculitis or malignancy,
• Agglutination:
Cold agglutinin disease
• Heinz bodies:
Unstable Hb, G6PD deficiency and oxidant stress
Slide 55
Special Lab. Examinations
Coombs antiglobulin test - immune hemolysis
Osmotic fragility test - spherocytosis
Autohemolysis- G6PD,PK, spherocytosis
Red cell enzyme assays- RBC enzyme defects
Membrane protein analysis- membrane defects
Red cell sickling, HbS- sickle cell anemia
Hemoglobin electrophoresis and HbA2, Hb F , HHb,etc -
Hemoglobinopathies and thalassemias
HAM and sucrose lysis tests and GPI-linked protein
analysis by flow cytometry- PNH
Oxygen dissociation curve- High oxygen affinity Hb
Slide 56
Case V
18 y o , male
Weakness, paleness, slight
icterus, splenomegaly, bile stones
Family history +
WBC: 5600/µl
Hgb: 9,6 g/dL
MCHC: %37
Plt: 300.000/µl
Retic: %9
?
Ind Bil: slightly elevated
LDH: elevated
Haptoglobin : low
Red cell osmotic fragility increased
Normal RBC
spherocyte
?
Slide 57
Case VI
38 y o
Cough , fever
WBC: 12.000/µl
Hgb: 11 g/dL
Hct: 22 %
MCV: 130
MCH: 40
MCHC: 36
RDW:28
Plt: 160.000/µl
Slide 58
Slide 59
Case VII
34 y o, male
2-3 weeks history of
•Decreased exercise capacity
•Paleness
•Headache, sore throat
2 days history of
•Cough and fever
•Red spots on the skin
CBC
WBC: 33.000/mm3
Hb: 7 g/dL
Retic: 1%
Plt: 12.000/mm3
Slide 60
Case IX
60 y o, female
Sudden onset
Pallor, palpitation
Slight scleral icterus
splenomegaly
CBC
Hb: 8 g/dL
WBC: 10.000/mm3
Plt: 450.000/mm3
Retic: 10%
What is your diagnosis?
What is your next step?
Indirect bilirubin: high
LDH: high
Haptoglobin: low
D/I: Coombs +
Slide 61
Case X
70 y o , male
•Under examination for
prostat enlargement
+One month history of
•Bone pain
•Symptoms of anemia
WBC: 8000/mm3
Hb: 8 g/dL
MCV: 88 fL
RDW: 14
Retic: 2%
Plt: 220.000/mm3
Slide 62
Morphologic abnormalities in hemolytic anemias
Polychromasia: Reticulocytes
Spherocyte :
Hereditary spherocytosis, immune hem. anemia,
burns, chemical injury to RBC
Elliptocytes:
Hereditary ovalocytosis,
Stomatocytes: Hereditary stomatocytosis, alcoholism
Acanthocytes: Spur cell anemia with liver disease,
abetalipoproteinemia
Echinocytes:
Pyruvate kinase deficiency, uremia