Medical Technology Department
Islamic University-Gaza
Practical of Clinical Hematology
Collected and prepared by
Mr. Mohammed O. Jaber
RBCs Abnormal morphology
Peripheral Blood Morphology
Abnormal erythrocyte morphology
Is found in pathological states that may be
abnormalities in
I. Red cell distribution.
II. Size (anisocytosis).
III. Hemoglobin content – Color Variation .
IV. Shape (poikilocytosis).
V. The presence of inclusion bodies in erythrocyte.

I.
Erythrocyte Distribution Abnormalities

Rouleaux formation
Stacking of RBCs due to
increased plasma proteins
coating RBCs

Agglutination
Antibody-mediated
clumping;
temperature dependent
I.
Erythrocyte Distribution Abnormalities
13- Rouleaux Formation:
Morphology:
Stacks of RBC's resembling a
stack of coins.
Found in:
- Hyperfibrinogenaemia
- Hyperglobulinaemia
I.
Erythrocyte Distribution Abnormalities
14- Red cell-agglutination:
Morphology:
Irregular clumps of red cells
Found in:
- Cold agglutinins
- Warm autoimmune hemolysis
Rouleaux Formation
Agglutination Reaction
Figure 2. The patient has autoimmune cold agglutinin disease and the
red blood cells (RBC) have clumped when placed on the cold slide
Schrier, S. ASH Image Bank 2002;2002:100344
II.

Variation in erythrocyte size (anisocytosis)
Normocyte: normal size of RBC, The average size
of an RBC is 7.2 μm with a range of 6.8 to 7.5 μm. The
nucleus of a small lymphocyte (± 8,µm) is a useful
guide to the size of a red blood cell.

Anisocytosis: Variations in size e.g.
Microcyte
2. Macrocyte
1.
A. Report RBC

size
• Microcytic: smaller than the normal RBC,(
<7.2 μm), and is associated with a decrease in
hemoglobin synthesis
Found in:
- Iron deficiency anemia.
- Thalassaemia.
- Sideroblastic anemia.
- Lead poisoning.
- Anemia of chronic disease.
II. Variation in erythrocyte size
(anisocytosis)

• Macrocyte: larger than the normal RBC (<8.2
μm) and is the result of a defect in nuclear maturation
or stimulated erythropoiesis. May be round or oval in
shape, the diagnostic significance being different.
Found in:
- Folate and B12 deficiencies (oval)
- Ethanol (round)
- Liver disease (round)
- Reticulocytosis (round)
Macrocytic Anemia: Macro-Ovalocytes
II. Variation in erythrocyte size
(anisocytosis)
Comment:
Most erythrocytes presented in the
picture are microcytes (compare
with the small lymphocyte). The
degree of hemoglobinization is
sufficient. Normal platelets and
single ovalocytes are present.
Staining: MGG
Magnification: x1000
1. microcyte 2. normocyte
III. Variation in erythrocyte

color
A normal erythrocyte has a pinkish-red color
with a slightly lighter-colored center (central pallor)
when stained with a blood stain, such as Wright.
 The color of the erythrocyte is representative of
hemoglobin concentration in the cell.

Under normal conditions, when the color, central
pallor, and hemoglobin are proportional, the
erythrocyte is referred to as normochromic.
III. Variation in hemoglobin content

• Hypochromia: increased central pallor and
decreased hemoglobin concentration, the central
pallor occupies more than the normal third of the
red cell diameter.
Found in:
o Iron deficiency
o Thalassaemia
any of the conditions leading to Microcytosis

III. Variation in hemoglobin content


• Polychromasia: Red cells
stain shades of blue-gray as a
consequence of uptake of both eosin
(by hemoglobin) and basic dyes (by
residual ribosomal RNA). Often
slightly larger than normal red cells
and round in shape - round
macrocytosis.
Found in:
Any situation with reticulocytosis for example bleeding, hemolysis or
response to heamatinic factor
replacement
Reticulocyte: Polychromasia
Polychromasia
Figure 2. Polychromasia may be seen in response to anemia
Maslak, P. ASH Image Bank 2004;2004:101122
IV. Shape Abnormalities of Erythrocytes

Poikilocytosis is the general term for mature
erythrocytes that have a shape other than the round,
biconcave disk.

Poikilocytes can be seen in many shapes.(e.g.
Acanthocyte, Spherocytosis,……)
Poikilocytosis
Figure 1. This is a periperal smear of a patient with
hereditary pyropoikilocytosis
Schrier, S. ASH Image Bank 2002;2002:100513
IV. Shape Abnormalities of Erythrocytes
Terminology
Description
Condition
Target cells
Central hemoglobin; target-shaped
Liver disease; thalassemia:
Abnormal Hgb; iron deficiency
Echinocyte
Short spicules, equally-spaced
Uremia, hypokalemia, artifact
Acanthocyte
Spiculated, irregular
Liver disease (alcohol),
Post-splenectomy
Spherocyte
Spherical, no central pallor
HS, Immune hemolytic anemia
Schistocyte
Fragmented RBC, helmet cells
MAHA, burns
Ovalocyte
Oval/elliptical shaped
Hereditary elliptocytosis,
Megaloblastic anemia
Sickle cell
bipolar spiculated shape
“banana” shaped
Hgb S-containing
hemoglobinopathy
Teardrop cell
single elongated extremity
Myelophthistic changes
Bite cells
Irregular gap in membrane
G6PD deficiency
III- Variation of red cells shape
(Poikilocytosis)
1.
Target cell: Red cell with a “target” or bull’seye appearance. The cell appears with a central
bull’s eye that is surrounded by a clear ring and
then an outer red ring.

Found in:
-Obstructive liver disease
- Severe iron deficiency
- Thalassaemia
- Haemoglobinopathies (S and C)
- Post splenectomy
Target Cells

Diagnostic possibilities
•
•
•
•
•
•
Liver disease
Hemoglobinopathy
Thalassemia
Iron deficiency
Post-splenectomy
Lipid disorders
IV. Abnormal
2.
Shape
Spherocytosis:
Morphology:
Red cells are more spherical. Lack the
central area of pallor on a stained
blood film.
Found in:
- Hereditary spherocytosis
- Immune haemolytic anemia
- Zieve's syndrome
- Microangiopathic haemolytic
Spherocytes
Spherocytes: Autoimmune Hemolytic Anemia
Spherocytes: Hereditary Spherocytosis
III- Variation of red cells shape
(Poikilocytosis)
8- Stomatocytosis:
Morphology:
Red cells with a central linear
slit or stoma. Seen as mouthshaped form in peripheral
smear.
Found in:
- Alcohol excess
- Alcoholic liver disease
- Hereditary stomatocytosis
- Hereditary spherocytosis
Stomatocyte
III- Variation of red cells shape
(Poikilocytosis)
 Ovalocyte : an elongated oval cell. They are a
result of a membrane defect.
Found in:
- Thalassaemia major.
- Hereditary ovalocytosis.
- Sickle cell anemia
III- Variation of red cells shape
(Poikilocytosis)
4- Elliptocytosis:
Morphology:
The red cells are oval or elliptical in shape. Long axis is twice the short
axis.
Found in:
- Hereditary elliptocytosis
- Megaloblastic anemia
- Iron deficiency
- Thalassaemia
- Myelofibrosis
Elliptocytes: Hereditary Elliptocytosis
III- Variation of red cells shape
(Poikilocytosis)
 Schistocyte: red cell fragments that are irregular
in shape and size. They are usually half the size of
the normal RBC; therefore, they have a deeper red
color.

Found in:
- Disseminated intravascular coagulation ( DIC )
- Micro angiopathic haemolytic anemia
- Mechanical haemolytic anemia
Schistocytes: Microangiopathic Hemolytic Anemia
schistocytes
Figure 1. Note the fragmented schistocytes, burr cells, and helmet cells
Schrier, S. ASH Image Bank 2001;2001:100249
III- Variation of red cells shape
(Poikilocytosis)
7- Schistocytosis:
Morphology:
Fragmentation of the red cells.
Found in:
- DIC
- Micro angiopathic haemolytic
anemia
- Mechanical haemolytic anemia
III- Variation of red cells shape
(Poikilocytosis)
6- Blister cell:prekeratocyte
Morphology:
Have accentric hallow area.
Resemble a women's handbag and may
be called pocket-book cell.
Found in:
Microangiopathic hemolytic anemia
Blister cell or prekratocyte
III- Variation of red cells shape
(Poikilocytosis)
10- Keratocytes (horn cell):
Morphology:
Part of the cell fuses back leaving
two or three horn-like projections.
The keratocyte is a fragile cell and
remains in circulation for only a
few hours.
Found in:
- Uraemia
- Severe burns
- EDTA artifact
- Liver disease
Keratocyte
Bite Cells
III- Variation of red cells shape
(Poikilocytosis)
12- Sickle Cells:
Morphology:
Sickle shaped red cells
Found in:
Hb-S disease
Sickle Cell Anemia: Hgb SS
III- Variation of red cells shape
(Poikilocytosis)
9- Burr (crenation ) cell:
Morphology:
Red cell with uniformly spaced,
pointed projections on their
surface.
Found in:
- hemolytic anemia
- Uremia.
- Megaloblastic anemia
Echinocytes (Burr Cells)
Hepatorenal Syndrome: Burr + Spur Cells
III- Variation of red cells shape
(Poikilocytosis)
11- Acanthocytosis:
Morphology:
are red blood cells with irregularly
spaced projections, these
projections very in width but usually
contain a rounded end
Found in:
- Liver disease
- Post splenectomy
- Anorexia nervosa and starvation
Acanthocytes (Spur Cells)
Figure 2. Higher magnification of the same smear showing the spur cells
( arrows), target cells, and polychromasia
Lazarchick, J. ASH Image Bank 2002;2002:100507
III- Variation of red cells shape
(Poikilocytosis)
 Teardrop: resembles a tear and usually smaller
than the normal RBC.
Found in:
- Bone marrow fibrosis
- Megaloblastic anemia
- Iron deficiency
- Thalassaemia
Figure 1. Dacryocytes (tear drop poikilocytes) are seen in the peripheral
blood of a patient with idiopathic myelofibrosis
Maslak, P. ASH Image Bank 2002;2002:100453
Envelope form cell
 Found in
– thalassemia
–Sickle cell anemia
V. Erythrocyte Inclusions with Wright’s Stain
Inclusion
Composition
Appearance
Basophilic
stippling
Precipitated
ribosomes
Evenly dispersed
Lead poisoning
fine or coarse granules thalassemia
other anemias
Howell-Jolly
bodies
DNA in origin
Nuclear fragment
Dense, round
blue granule
Post-splenectomy
Pappenheimer Iron-containing
bodies
granules
Small blue granules
in clusters
Anemias
Heinz bodies
round blue precipitates G6PD
Cabot Rings
Organism
Denatured
hemoglobin
remnants of
nuclear membrane
Condition
Reddish-blue threadlike Severe anemia,
rings
Lead poisoning
Small blue inclusion
Malaria
Babesiosis
V. Erythrocyte inclusion bodies
1- Howell-Jolly Bodies:
Morphology:
Small round cytoplasmic red
cell inclusion with same
staining characteristics as
nuclei
Found in:
- Post splenectomy
- Megaloblastic anemia
Howell-Jolly Body
Figure 1. Howell-Jolly bodies are small dense particles seen
in the cytoplasm of this erythroid precursor
Maslak, P. ASH Image Bank 2005;2005:101350
V. Erythrocyte inclusion bodies
2- Siderotic Granules
(Pappenheimer Bodies)
RBCs which contain no
hemoglobin iron granules. They
appear as dense blue, irregular
granules which are unevenly
distributed in Wright stained
RBCs. Pappenheimer bodies can
be increased in hemolytic
anemia, infections and postsplenectomy.
Figure 2. Multiple RBCs containing Pappenheimer bodies are
seen in htis view
Lazarchick, J. ASH Image Bank 2004;2004:101168
V. Erythrocyte inclusion bodies
3- Basophilic stippling:
Morphology:
Considerable numbers of small
basophilic inclusions in red cells.
Found in:
- Thalassaemia
- Megaloblastic anemia
- Hemolytic anemia
- Liver disease
- Heavy metal poisoning.
Tear Drop Cells
Figure 3. There is extensive course basophilic stippling of
the red blood cells (RBC) in this patient who has had
exposure to toxic levels of lead
Schrier, S. ASH Image Bank 2002;2002:100344
Basophilic Stippling
V. Erythrocyte inclusion bodies
4- Heinz Bodies:
Represent denatured hemoglobin
(methemoglobin - Fe+++) within a
cell. With a supravital stain like
crystal violet, Heinz bodies appear
as round blue precipitates.
Presence of Heinz bodies indicates
red cell injury and is usually
associated with G6PD-deficiency.
Heinz Bodies
Figure 2. Heinz Body Preparation. RBC are incubated
supravitally in new Methylene blue to identify precipitates of
oxidatively denatured hemoglobin.
IV -Erythrocyte inclusion bodies
5- Cabot Rings:
Reddish-blue threadlike rings in
RBCs of severe anemia's. These
are remnants of the nuclear
membrane or remnants of
microtubules and appear as a
ring or figure 8 pattern.
 Very rare finding in patients with
1. Megaloblastic anemia.
2. severe anemia's.
3. lead poisoning.
4. Dyserythropoiesis.
Cabot rings
V. Erythrocyte inclusion bodies
6- Parasites of Red Cell:

Two organisms are have a
tendency to invade the RBCs.
1.
All 4 species of the malaria
parasite will invade RBCs. We
will see the Plasmodium of
different species in RBCs.
2.
Bebesia microti
Malaria
RBCs Abnormal morphology
Depiction of red blood cell
morphologies that may
appear on a peripheral
smear, showing:
(A) basophilic stippling, (B)
Howell-Jolly bodies, (C)
Cabot's ring bodies and (D)
Heinz's bodies.
Normal Peripheral Smear
Reticulocyte Manual Count by Supravital
Stain: Normal Count
Reticulocytes: Elevated Count
RBC Inclusions: Composite
Hypochromic Microcytic RBC
Normal
Hypochromic microcytic
Severe Hypochromia: Iron Deficiency
Anemia
Mixed Population: Treated Iron Deficiency
Anemia
Microcytic Hypochromia: Alpha
Thalassemia (a-/--)
Morphologic Changes in Liver Disease
Target Cells
Spur Cells