Anaemia

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Anaemia
Prof. A. B. Skotnicki M.D. Ph.D.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia
Decreased haemoglobin
concentration and/or PCV
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Internal iron exchange.
Absorption - about
1 mg/d is required
from the diet in
men, 1.4 mg/d in
women
transferrin
saturation 20 to
60%
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Iron storage and transport
Tissue
ferritin
Serum transferin
20 umol/l
Bone
Marrow
Erythroblasts
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Classification of anaemia

Morphological

Based on red
cell
measurement

Aetiological

Based on cause
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Aetiological classification of anaemia
↓ Hb ↓ ER
Excessive
blood loss
-haemorrhage
Haemolitica
anaemias
Post –
haemorrhagic
anaemia
Inadequate
production
of red cells
Excessive red
cell destruction
- decreased
Aplastic anameia
Bone marrow infiltrattion
abnormal
-
Cytoplasmic
defect
↓ Fe
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
Nuclear
defect
↓ B12
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Morphological classification of anaemia
Acute blood loss
Haemolysis
Bone marrow aplasia
Bone marrow infiltration
↓ Fe
↓ MCV
↓ MCH
Microcytic
hypochromic
anaemia
Chronic
disease
MCV and
MCH normal
Normocytic
normochromic
anaemia
B12
↓ fol.ac.
↓
↑ MCV
↑ MCH
Macrocytic
hyperchromic
Megaloblastic
anaemia
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia – signs and symptoms


General signs and symptoms universal
for all anaemias
Signs and symptoms specific for a
particular cause
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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General symptoms of anaemia
↓ Hb
↓ O2 carrying capacity of blood
TISSUE HYPOXIA
Clinical manifestations
Palpitations
Tachycardia
Heart murmurs
dyspnoea
pallor
Compensatory mechanisms
mobilised to contract hypoxia
Cardiac overactivity
Cadiorespiratory
insufficiency
Skin vasoconstriction
redistribution
of blood flow
(brain, heart)
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia – general signs and symptoms
CSN:
Pale skin & mucous
membranes
CVS:
•Tachycardia
•Functional murmur
•Stenocardiac pain
•Headaches
•Tinnitus
General:
•Shortness of breath
•Fatigue
•Weakness
•Susceptibility to
infections
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia – major types
Iron deficiency anaemia Nutritional factor
deficiency
 Megaloblastic anaemia
 Haemolytic anaemia
 Aplastic anaemia
 Anaemia of chronic disease

Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Normal erythropoiesis
Fe
B12
haemoglobinisation
RBC production
HB N
=
N
E
MCV=90 fl
MCHC=32 g/l
MCH=32 pg
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Erythropoiesis in IDA or after bleeding
Fe
B12
haemoglobinisation
RBC production
HB <N
=
N/>N
E
MCV=70 fl
MCHC=28 g/l
MCH=25 pg
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Iron deficiency anaemia (IDA) - causes
Inadequate
intake
Increased
requirement
Chronic blood loss
Iron
malabsorbtion
• GI
• Urinary Tract
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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IDA – causes of chronic blood loss
Haematemesis
Haemoptysis
Gastrointestinal tract
bleeding:
•Hiatus hernia
•Gastritis haemorrhagica
•Peptic ulcer
•Gastric cancer
•Intestinal polyposis
•Colonic cancer
•Colitis ulcerosa
•Haemorrhoidal varices
Urinary tract
bleeding –
haematura:
•Renal disorders
•Inflammation
•Tumour
•Urinary tract
•Calculosis
•Polyps
•Urinary bladder
tumours
Genital tract bleeding:
•Menorrhagiae
•Metrorrhagiae
•Uterine myoma
•Melaena
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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IDA - signs and symptoms
General signs and
symptoms PLUS
tissue asiderosis
Hair:
•Fragility, coming out
•Early gray
Skin:
•Dry, cracked
•Cheilitis angularis
•rhagades
Eyes:
•Bluish sclera
Nails:
•Brittle, spoon nails
•Atrophic changes
Tongue
•Glossitis anaemica
Dysphagia
Plummer-Vinson syndrome
Neurovegetative dystonia
Pica
Gastric
troubles
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Moderately severe iron deficiency anaemia

This example of moderately
severe iron deficiency anaemia
shows anisocytosis,
anisochromasia, hypochromia,
microcytosis and poikilocytosis.
The poikilocytes include several
particularly long elliptocytes,
sometimes referred to as 'pencil
cells'. Elliptocytes are
characteristic of iron deficiency
but not pathognomonic.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Severe iron deficiency anaemia

Blood film from a
patient with severe
iron deficiency
anaemia. The film
shows anaemia,
microcytosis,
hypochromia,
anisocytosis,
anisochromasia and
poikilocytosis.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Pallor in iron deficiency anaemia

The hand of a patient
with iron deficiency
anaemia showing pallor.
The hand of a nonanaemic person is
pictured for comparison.
Pallor is a non-specific
feature of anaemia.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Pale conjunctiva in iron deficiency anaemia

The best places to
check for pallor that
may indicate anaemia
are the conjunctiva,
the nail beds and the
palms of the hands.
This patient with iron
deficiency anaemia
has conjunctival
pallor.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Pallor in iron deficiency anaemia

Pallor in a patient
with iron deficiency
anaemia. The
patient's hand is
pictured together
with the hand of a
healthy person.
(Courtesy of Dr D.
Samson.)
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Oral changes in iron deficiency anaemia

Angular cheilosis and
atrophic glossitis in iron
deficiency anaemia. These
features are typical of
moderately severe iron
deficiency anaemia and
indicate the effect of iron
deficiency on tissues other
than the bone marrow.
(Courtesy of Dr D.
Samson.)
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Cheilitis Angularis in IDA
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Koilonychia in iron deficiency anaemia

Koilonychia or spoonshaped nails in iron
deficiency anaemia.
Koilonychia has a high
degree of specificity for
iron deficiency but it is
a relatively uncommon
feature, occurring only
in severe chronic iron
deficiency.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Typical changes in blood count in IDA

Normal Blood Count









Hb
14 g/dl
RBC 4,50 x 10^12/l
PCV 40 %
MCV 90 fl
MCH 30 pg
Ret
0,5 %
WBC 7,5 x 10^9/l
Differential normal
Platelets
400x10^9/l

Blood Count in IDA









Hb
7,5 g/dl
RBC 4,05 x 10^12/l
PCV 26%
MCV 64 fl
MCH 18,5 pg
Ret
2,6%
WBC 7,5 x 10^9/l
Differential normal
Platelets
530x10^9/l
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Iron deficiency is NOT a
diagnosis but a symptom
Aetiology
?
Iron
Deficiency
anaemia
Clinical
& laboratory
findings
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Iron deficiency anaemia

53 old male






Tiredness
Hb 7 g/l
MCV 69 fl
Serum ferritin 8ug/l
Occult faecal blood test positive (+)
Colonoscopy
•Carcinoma of the colon
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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22 years old patient with ACD (Hodgkin’s lymphoma)
30
25
Fe (umol/l) - normal values
20
Hb (g/l)
15
Hb - norm al values
Fe (um ol/l)
10
5
0
XI 2000
XII 2000
IV 2001
V 2002
TIME
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Megaloblastic Anaemia

Abnormal changes in blood cell
formation leading to macrocytic
anaemia and varying degrees of
pancytopenia as a result of abnormal
DNA synthesis because of single or
combined deficiency of folate
and/or vitamin B12
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Normal erythropoiesis
Fe
B12
haemoglobinisation
RBC production
HB N
=
N
E
MCV=90 fl
MCHC=32 g/l
MCH=32 pg
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Erythropoiesis in B12 deficiency
Fe
B12
haemoglobinisation
RBC production
HB N
=
<N
E
MCV=100 fl
MCHC=32 g/l
MCH=40 pg
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Megaloblastic anaemia - causes
Inadequate
intake
Malabsorbtion
Increased
requirement
Disturbed
metabolism
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Megaloblastic anaemia - causes

COBALAMIN DEFICIENCY.
 Inadequate intake:
vegetarians (rare)
 Malabsorption: Defective
release of cobalamin from
food:Gastric achlorhydria,
Partial gastrectomy, Drugs
that block acid secretion
 Inadequate production of
intrinsic factor (IF): Pernicious
anemia; Total gastrectomy:
Congenital absence or
functional abnormality of IF
Disorders of terminal ileum
 Competition for cobalamin
 Other

FOLIC ACID DEFICIENCY



Inadequate intake:
unbalanced diet (common in
alcoholics, teenagers, some
infants)
Increased requirements:
Pregnancy, Infancy,
Malignancy, Increased
hematopoiesis, Chronic
exfoliative skin disorders
Malabsorption: Tropical sprue,
Nontropical sprue, others
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Megaloblastic anaemia - causes
Cause
1. Dietary deficiency:
2. Malabsorbtion:
•Atrophic gastritis
•Hipochlorchydria
•Lack of intrisinc factor
•Small bowel diseases
•Post gastrectomy
3. Increased demands:
•Pregnancy
B12 deficiency
Folic acid deficiency
rarely
often (alcohol abuse, parenteral
nutrition, age)
+++
+++
+
+
−
−
++
-
−
++
−
+
+
+
4. Disturbed metabolism:
•anticonvulsives
•cytostatics
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Megaloblastic anaemia– symptoms and signs
CSN:
•Headaches
•Tinnitus
•Visual disturbances
•Optic nerve disturbances
•Psychiatric disturbances
•Irritability
•Sleepiness
•Dementia
•Peripheral neuropathy
•Paresthesia
•Pins and needles
•Unsteady gait
•Reduced Sensation
•Imbalance
•Dysuria
•Reduced heat and cold
sensibility
Specific PLUS
General signs and
symptoms
•
Average age – 60
Often - women
•
•
•
•
•
•
•
Glossitis Hunteri
• smooth
• Reddened
• Burning
• Reduced in size
Loss of appetite
Loss of taste
Loss of body weight
Abdominal pains
Atrophic gastritis
Diarrhoea
Achlorchyrdia
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Blood film in megaloblastic anaemia

In megaloblastic anaemia
the most characteristic
features in the peripheral
blood film are
hypersegmented
neutrophils and
macrocytes, particularly
oval macrocytes [arrow].
The neutrophil shown
has six lobes and is
therefore classified as
hypersegmented
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Haemolytic anaemia
 Decrease
in the total number of
circulating erythrocytes that is
caused by premature
destruction or removal of red
cells from the circulation
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Haemolytic anaemia

Classifications of HA according to
 Type of defect
 Site of defect
 Site of haemolisis
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Classification of HA according to
Type of defect

Hereditary



Membrane defect
Metabolic defect
Hemoglobinopathies

Acquired






Immunologic defect
Mechanical defect
Intravascular coagulopathy
March hemoglobinuria
Infection
Membrane abnormality
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Classification of HA according to
Type of defect

Hereditary

Membrane defect

Acquired

• Drug-induced hemolysis
• Isoimmune and alloimniune
hemolysis (neonatal and delayed
transfusion reactions)
• HS
• Hereditary elliptocytosis

Metabolic defect
• GdPD deficiency
• PK deficiency


Mechanical defect
• Rapid turbulent flow of blood,
tumors, hypertension, aortic
stenosis, Prosthetic valve leaks
Hemoglobinopathies
• Thalassemias
• Sickle cell diseases
• Other
hemoglobinopathies
Immunologic defect




Intravascular coagulopathy
March hemoglobinuria
Infection
Membrane abnormality (stem
cell abnormality)
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Classifications of HA according to
Site of defect

Intracorpuscular factors



Red cell membrane
abnormalities (HS and
related abnormalities PNH)
Hemoglobinopathies
(Thalassemias, Sickle cell
disease and related
hemoglobinopathies,
Methemoglobinemia,
Unstable hemoglobin
diseases )
Enzymopathies (G6PD
deficiency Others)

Extracorpuscular factors




Antibodies (Autoimmune
hemolytic anaemia,
transfusion-related
haemolytic reactions, Drugrelated hemolytic reactions)
Mechanical or traumatic
factors (Prosthetic heart
valves, High-flow red cell
damage, Intravascular
coagulopathy)
Infections (Bacterial,
Parasitic)
Cell membrane lipids (Liver
disease, Lipid disorders)
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Classifications of HA according to
Site of Haemolysis

Intravascular
hemolysis



Traumatic hemolysis
Immune hemolysis
Infections

Extra vascular
hemolysis





Autoimmune hemolytic
anemia
Red cell membrane
defects
Spur cell anaemia
Red cell metabolism
defect
Unstable haemoglobin
diseases
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Clinical signs and symptoms
of haemolytic anaemia


General signs and symptoms universal
for all anaemia
Signs and symptoms specific
haemolysis



Jaundice
Increased billirubin (unbound)
Increased reticulocitosis
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Example of blood film in HA


Microangiopathic
haemolytic anaemia
Blood film showing the
features of
microangiopathic
haemolytic anaemia in
haemolytic uraemic
syndrome. There are
schistocytes including
one microspherocyte
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Aplastic anaemia

Acellular or hypocellular marrow that

Etiology:
causes bone marrow failure and lower
level of cell production, leading to
pancytopenia.


Idiopathic
Secondary
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Causes of Secondary Aplastic Anaemia

Drugs and toxins




Chloramphenicol
Cancer chmotherapy
Chemicals
Infections




Viral hepatitis
CMV
Infectious
mononucleosis
Parvovirus 19



Proleukaemic and
leukaemic
conditions
Paroxysmal
nocturnal
haemoglobinuria
Genetic or
constitutional
conditions
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Bone marrow in AA

Normal Bone
marrow
WBC
PLT

Bone marrow in
AA
Residual haemopoesis
RBC
Fat cells
Fat cells
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Signs and symptoms of AA
 The



results of pancytopenia
Anaemia (general signs)
Thrombocytopenia (bleeding
tendency)
Granulocytopenia
(infections)
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Normal bone marrow (right) and in aplastic anaemia (left) trephine
biopsies
normal
AA
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia of chronic disease (ACD)
 Common
type of anaemia
that occurs in patients who
present with any of several
chronic inflammatory and
malignant diseases
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia of chronic disease (ACD)

Anaemia of chronic disease


caused by a defect in incorporation of iron
into haemoglobin as a consequence of
infection, inflammation or malignant
disease.
Bone marrow iron stores are usually normal
or increased. The anaemia is initially
normocytic and normochromic but when it
becomes severe is hypochromic and
microcytic.
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Signs and symptoms of ACD
 General
signs and symptoms of
anaemia
 Blood film as in IDA
 No tissue asiderosis
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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ACD & IDA: clinical & laboratory differences
Feature
ACD
IDA
Severity
+
++
Tissue asiderosis
-
+++
Chronic disorder
+++
+
++
-
Serum iron
↓
↓↓
Serum ferritin
↑
↓
Serum transferin
↓
↑
TIBC
↓
↑
↑ ESR: fever; ↑WBC; ↑PLT; pain;
lymph nodes ↑
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Signs and symptoms in anaemia
Anaemia
Signs and symptoms
Aplastic
Marrow failure
Iron deficiency
Tissue asiderosis
B12 &
follic acid deficiency
Neuro & gastrointestinal
Chronic disease
Without tissue asiderosis
Haemolytic
Haemolysis
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Anaemia of chronic disease bone marrow
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Comparison of blood films in anaemias
Normal
Macrocytic
IDA
Haemolytic
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Fe, TIBC and UIBC
TIBC
60 umol/l
Fe
20 umol/l
UIBC
NORMAL
Fe overload
IDA,
pregnancy
Infections
cancers
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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Oral iron absorbtion test
Fe serum concentration
(umol/l)
50
upper limit of the
normal value
lower limit of the
normal value
impaired absorbtion
(flat curve)
iron deficiency with
increased absorbtion
40
30
20
10
0
1
3
6
hours
Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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MCV in anaemia
Microcytic (MCV<N)
Iron deficiency
Fe<N, Ferritin<N, TIBC>N

Chronic disease
Fe>N, Ferritin=,>N

Talasemia
Fe >N, Ferritin >N

Normocytic
(MCV=N)
Aplastic
Reticulocytes < N
Macrocytic
(MCV>N)
B12 <N

Haemolytic
Reticulocytes > N
Folic acid <N

Acute blood loss
Reticulocytes > N

Department of Haematology, Collegium Medicum Jagiellonian University, Kraków, Poland
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