Differential diagnosis of hypochromic anemia.ppt

Discuss hypochromic anemia

1. Differential diagnosis of
hypochromic
anaemia

2. Definition of Anemia
Anaemia is the most common hematological
disorder by far.
It is critical to know how to evaluate /
determine its cause / treat.

3. Normal Red Cells
No nucleus
Biconcave discs
Center 1/3 pallor
Pink cytoplasm (Hb filled)
Cell size 7- 8 µ -
Negative charge –
100-120 days life span

4. Screening Tests – Anemia
Clinical Signs and symptoms of Anemia
Look for bleeding – all possible sites
Look for the causes for anemia
Routine Hemoglobin examination

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The Three Primary Measures
Measurement Normal
Range
A.RBC count (RCC) 5 million
B.Hemoglobin 15 g/dl
C. (PCV) 45
A x 3 = B x 3 = C - This is the rule of thumb
Check whether this holds good in a given result
If not -indicates micro or macrocytosis or hypochro.

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The Three Derived Indicies
Measurement Normal
Range
A.RBCs 5 million
B.Hemoglobin 15 g/dl
C.Hematocrit 45 %
MCV C ÷ A x 10 =90 fl
MCH B ÷ A x 10 =30 pg
MCHC (%)B ÷ C x 100=33%

7. Causes of Anemia
1.Decreased production of Red Cells
- Hypo proliferative, marrow failure
2.Increased destruction of Red Cells
- Hemolysis (decreased survival of RBC)
3.Loss of Red Cells due to bleeding
- Acute / chronic blood loss
(hemorrhagic)

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Hypoproliferative Anemias
Failure of cell
maturation
Nuclear
breakdown
Cytoplasmic
breakdown
Megaloblastic Anemia
Defective DNA synthesis
Folate or B
12
deficiencyHaem defectGlobin defect
Thalassemia
Sickle cell AFePhorph
IDA, SA

9. RETICULOCYTE COUNT %
Normal
0.2- 2%
• ‘RBC to be’ or Apprentice RBC
• Fragments of nuclear material
• RNA strands which stain blue

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Reticulocyte
No definite nucleus
Reticulum of RNA
Deep blue staining
Light blue cytoplasm
Cell size about 10 µ

11. Reticulocytes
Leishman’sSupravital

12. Reticulocyte Production
Index
For example, the RPI is calculated as
follows
Reticulocyte count 9%
Hb content 7.5 g%
1.Correction for Anemia
= 9 x (7.5 ÷ 15) = 9 x 0.5 = 4.5 %
2.Correction for life span
4.5 ÷ 2 = 2.25 %
3.Thus, the RPI is 2.25

13. Anemia
Hypoproliferative Hemolytic
RPI < 2 RPI > 2
Hb% < 12, Hct < 38%

14. Workup – Third Test
The next step is ‘What is the size of RBC’ ?
MCV indicates the Red cell volume (size)
Both the MCH & MCHC tell Hb content of RBC
We are dealing with either
Hypoproliferative Anemia (lack of raw material)
Maturation defect with less production
Bone marrow suppression (primary/ secondary)

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Red Cell Size

16. Mean Cell Volume (MCV)
RBC size is measured indirectly by
The Mean Cell Volume (MCV) and RDW
Microcytic
< 80 fl
MCV
Normocytic Macrocytic
80 -100 fl > 100 fl
< 6.5 µ 6.5 - 9 µ > 9 µ

17. MCV
Microcytic
MCV
Normocytic Macrocytic
Iron Deficiency (IDA)
Chronic Infections
Thalassemias
Hemoglobinopathies
Sideroblastic Anemia
Chronic diseases, CKD
Early IDA
Hemoglobinopathies
Primary marrow disorders
Combined deficiencies
Increased destruction
Megaloblastic anemias
Liver disease/alcohol
Hemoglobinopathies
Metabolic disorders
Marrow disorders
Increased destruction

18. 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 there any hemo-parasites in the RBC ?
platelet distribution adequate ?

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IDA -CBC

20. Severe Hypochromia

21. Microcytic Hypochromic -
IDA

22. IDA Summary
Microcytic MCV < 80 fl, RBC < 6 µ
Hypochromic MCH < 27 pg, MCHC <
30%
Retic. count May be > 2 %
Serum ferritin Very low
TIBC Increased > 340 (µg/dL)
BM Iron stain Iron is Absent

23. Ringed Sideroblasts in BM
Prussian Blue Stain

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Anemia - 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%
look for blood loss – acute / chronic / occult
Is it hypo-proliferative or hemolytic or hemorrhagic Anemia
If hypo proliferative – Microcytic or Macrocytic? (MCV, RDW)
If microcytic – IDA or others – Sr Ferritin TIBC, BM Iron
If macrocytic – Megaloblastic (B12, FA) or Normoblastic BM
If normocytic – Anemia of chr. Disease –
Peripheral smear study for RBC size, shape, colouration etc.
If retic. count is -
↑
; Hb EP, spl. tests

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RBC Size – Anisocytosis
Different sizes of RBC

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Poikilocytosis
Different Shapes of RBC

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Definition of Anemia
Inability of blood to supply tissues with
adequate oxygen for proper metabolic function.
Diagnosis made by patient history, physical
examination, signs and symptoms, and
hematological laboratory findings.

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In healthy individuals, about 1% of RBCs lost
daily.
 Bone marrow continuously produces RBCs to
equal daily loss.
 Reticulocyte count is a lab measurement of
this loss.

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MCV
Mean cell volume
MCV is average size of RBC
MCV = Hct x 10
RBC (millions)
If 80-100 fL, normal range, RBCs considered
normocytic
If < 80 fL are microcytic
If > 100 fL are macrocytic
Not reliable when have marked anisocytosis

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MCH
MCH is average weight of hemoglobin
per RBC.
MCH = Hgb x 10
RBC (millions)

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MCHC
MCHC is average hemoglobin concentration per
RBC
MCHC = Hgb x 100
Hct (%)
If MCHC is normal, cell described as
normochromic
If MCHC is less than normal, cell described as
hypochromic
There are no hyperchromic RBCs

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RDW
Most automated instruments now provide an
RBC Distribution Width (RDW)
An index of RBC size variation
May be used to quantitate the amount of
anisocytosis on peripheral blood smear
Normal range is 11.5% to 14.5% for both men
and women

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Other Tests
(In the Diagnosis of Anemia)
Hemoglobin Electrophoresis
Antiglobulin Testing
Osmotic Fragility
Sugar Water Test
Ham’s Test
RBC Enzymes
B12, Fe, TIBC, Folate Levels

34. Introduction
Anemia is defined as a decrease in
erythrocytes and hemoglobin, resulting in
decreased oxygen delivery to the tissues.

35. Relative (pseudo) anemia

 RBC mass is normal, but plasma volume is
increased.
Secondary to an unrelated condition and
can be transient in nature
 Causes include conditions that result in
hemodilution, such as pregnancy and volume
overload.

36. Reticulocyte count normal;
normocytic/normochromic anemia

37. Absolute anemia
RBC mass is decreased, but plasma volume is
normal. This is indicative of a true decrease in
erythrocytes and hemoglobin.
 Mechanisms involved include:
1) Decreased delivery of red cells into
circulation
a) Caused by impaired or defective production
b) Bone marrow fails to respond;
reticulocytopenia

38. 2) Increased loss of red cells from the
circulation
a) Caused by acute bleeding or
accelerated destruction (hemolytic)
b) Bone marrow can respond;
reticulocytosis

39. Impaired or Defective Production Anemia
Iron-deficiency anemia
Most common form of anemia in the United
States
Prevalent in infants and children, pregnancy,
excessive menstrual flow, elderly with poor
diets, malabsorption syndromes, chronic blood
loss (GI blood loss, hookworm infection)

40. Anemia of chronic disease
(ACD)
Due to an inability to use available iron for
hemoglobin production.
Impaired release of storage iron associated
with increased hepcidin levels
Hepcidin is a liver hormone and a positive
acute-phase reactant.
It plays a major role in body iron regulation
by influencing intestinal iron absorption and
release of storage iron from macrophages.

41. Inflammation and infection cause hepcidin
levels to increase; this decreases release
of iron from stores.
Laboratory: Normocytic/normochromic
anemia, or slightly
microcytic/hypochromic anemia;
increased ESR; normal to increased
ferritin; low serum iron and TIBC

42. Associated with persistent infections,
chronic inflammatory disorders (SLE,
rheumatoid arthritis, Hodgkin lymphorna,
cancer).

43. Sideroblastic anemia
Caused by blocks in the protoporphyrin
pathway resulting in defective hemoglobin
synthesis and iron overload.
Excess iron accumulates in the mitochondrial
region of the immature erythrocyte in the bone
marrow and encircles the nucleus; cells are
called ringed sideroblasts.
Inclusions are siderotic granules (Pappenheimer
bodies on Wright's stained smears).

44. Lead poisoning
Multiple blocks in the protoporphyrin
pathway affect heme synthesis.
Seen mostly in children exposed to lead-
based paint

45. Laboratory: Normocytic/normochromic
anemia with characteristic coarse
basophilic stippling

46. IDA
Red cell indices and blood film
Even before anaemia occurs, the red cell
indices fall and they fall progressively as the
anaemia becomes more severe.
The blood film shows hypochromic, microcytic
cells with occasional target cells and pencil
‐
shaped poikilocytes .

47. The reticulocyte count is low in relation to
the degree of anaemia.
 When iron deficiency is associated with
severe folate or vitamin B12 deficiency, a
‘dimorphic’ film occurs with a dual population
of red cells of which one is macrocytic and
the other microcytic and hypochromic; the
indices may be normal.

48. A dimorphic blood film is also seen in patients
with iron deficiency anaemia who have
received recent iron therapy and produced a
population of new haemoglobinized normal
‐
sized red cells and when the patient has been
transfused.
The platelet count is often moderately raised
in iron deficiency, particularly when
haemorrhage is continuing.

49. Bone marrow iron
Bone marrow examination is not essential to
assess iron stores except in complicated
cases.
In iron deficiency anaemia there is a complete
absence of iron from stores (macrophages)
and from developing erythroblasts .

50. Serum iron and total iron
‐
binding capacity
The serum iron falls and total ironbinding
‐
capacity (TIBC) rises so that the TIBC is less
than 20% saturated .
This contrasts both with the anaemia of chronic
disorders.
It also contrasts with other hypochromic
anaemias where the serum iron isnormal or even
raised.

51. Serum ferritin
A small fraction of body ferritin circulates in
the serum, the concentration being related to
tissue, particularly reticuloendothelial, iron
stores.
The normal range in men is higher than in
women .
In iron deficiency anaemia the serum ferritin
is very low .

52. A raised serum ferritin indicates:
Iron overload .
Excess release of ferritin from damaged
tissues.
An inflammation.
- The serum ferritin is normal or raised in the
anaemia of chronic disorders.

53. Anaemia of chronic disorders
One of the most common anaemias occurs in
patients with a variety of chronic inflammatory
and malignant diseases
The characteristic features are:
Normochromic, normocytic or mildly hypochromic
(MCV rarely <75 fL) indices and red cell
morphology.
Mild and nonprogressive anaemia (haemoglobin
‐
rarely <90 g/L) – the severity being related to
the severity of the disease.

54. Both the serum iron and TIBC are reduced.
The serum ferritin is normal or raised.
Bone marrow storage (reticuloendothelial)
iron is normal but erythroblast iron is reduced
.

55. The pathogenesis of this anaemia appears to
be related to decreased release of iron from
macrophages to plasma because of raised
serum hepcidin levels, reduced red cell
lifespan and an inadequate erythropoietin
response to anaemia caused by the effects of
cytokines such as IL1 and tumour necrosis
‐
factor (TNF) on erythropoiesis.

56. The anaemia is corrected by successful
treatment of the underlying disease.

57. Sideroblastic anaemia
This is a refractory anaemia defined by the
presence of many pathological ring
sideroblasts in the bone marrow.
These are abnormal erythroblasts containing
numerous iron granules arranged in a ring or
collar around the nucleus instead of the few
randomly distributed iron granules seen when
normal erythroblasts are stained for iron.

58. Sideroblastic anaemia is diagnosed when 15%
or more of marrow erythroblasts are ring
sideroblasts.

59. IDA Chronic
inflammatory
of malignancy
thalassaemiaSideroblastic
anaemia
MCV/MCH Reduced in
relation
to severity of
Anaemia
Normal or mild
reduction
Reduced; very
low for
degree of
anaemia
Usually low in
congenital
type but MCV
usually
raised in
acquired type
SERUM IRON Reduced Reduced normal raised
TIBC Raised Reduced Normal Normal
S. FERRITIN Reduced Normal or
raised
Normal Raised
BONE
MARROW
IRON
STORES
Absent Present Present Present
ERYTHROBLA
STS IRON
Absent Absent Present Ring forms
HB
ELECTROPH
ORESIS
Normal Normal Hb A2 raised
in β form
Normal