M06 - Blood Cell Anomalies

MODULE 6
BLOOD CELL ANOMALIES

At the end of the module, students should be able to:
1. Recall the normal morphologic presentations of erythrocytes and leukocytes.

2. Discuss the preparation of a stained peripheral blood smear for the microscopic
evaluation of blood cells.
3. Compare the normal and abnormal morphologies of blood cells.
4. Determine disease correlations that lead to such anomalies
UNIT 1: RED CELL ANOMALIES
Recall the appearance of a normal red cells. Provide the

expected values of the indices below to characterize a
ENGAGE normocyte.
INDICES NORMAL VALUES

MCV
MCH
MCHC
VI
CI
SI
MCAT
Being able to fully understand the normal morphologic appearance of a red cell is
crucial in the evaluation of abnormalities that may affect both the structure and function of
the red cell. Any variation in the normal appearance, that can be reflected by any deviation
in the red cell indices is termed as an ANOMALY. Red cell anomalies have different
categories, each indicating different disorders or disease correlations.
In the hematology laboratory, examination of a peripheral blood smear is conducted
to evaluate cellular morphology, determine the presence of anomalies and to validate the
results released by an automated analyzer. The procedures for peripheral blood smear
preparation and evaluation are detailed as follows:
MATERIALS
Blood collection set Modified Wright stain set
Slides Compound microscopes
Immersion Oil Coplin Jars
Filter paper or tissue paper Distilled water
SAINT LOUIS UNIVERSITY
SCHOOL OF NATURAL SCIENCES
DEPARTMENT OF MEDICAL LABORATORY SCIENCE
Name: _______________________________ Rating: _______________

Instructor: ___________________________ Date: _________________
EXPERIMENT 11
STAINED RED CELL EXAMINATION
OBJECTIVES
1. Describe the morphological features of a normal RBC.
2. Discuss the different abnormalities in RBC morphology.
3. Correlate morphological abnormalities to different physiologic and pathologic
processes.
MATERIALS
Compound Microscope
Immersion oil
Stained blood smear from previous experiments.
Charts and atlas
PROCEDURE
1. Focus the stained smear under LPO and locate an area where cells are evenly distributed
and do not overlap.
2. Transfer to oil immersion objective and examine the RBC paying particular attention to
red cell size, shape and staining reactions. Take note of the presence of inclusion bodies
in the RBC.
3. Report all abnormalities noted.
DRAWINGS:
1. Types of anisocytes compared to a normocyte.

2. Staining properties compared to a normochromic RBC
3. Types of poikilocytosis
4. RBC inclusion bodies
QUESTIONS FOR RESEARCH:

1. How do you describe the microscopic appearance of blood cells in a stained smear?
2. What is meant by zone of morphology? Why is it important in the red cell examination?
3. What are manual errors that could falsely distort the morphology of a red cell? Explain.
PROCEDURE
1. Smear preparation (Fig. 6-1):
Blood sample: Freshly collected blood (capillary puncture or EDTA-blood)
A. Place a drop of blood approximately 2 mm in diameter at one end of the slide.
B. A smooth spreader slide is placed at an angle of 40 o touching the drop of blood.
C. Allow the blood to spread along the narrow edge of the spreader.
D. With even force, push the spreader quickly and with single stroke away from the
blood drop, covering the length of the slide.
E. Air-dry the smear and label on the thick portion.
Figure 6-1. Peripheral Blood Smear Preparation

2. Staining:
A. Place the slide directly in a coplin jar containing fixative solution and dip 2-3X.
B. Directly transfer the slide to the next coplin jar containing Eosin and dip 5 times.
C. Blot all excess stains in filter paper or tissue paper.
D. Dip the slide 5 times into a coplin jar containing Methylene Blue.
E. Wash briefly in distilled water and allow to dry.
Figure 6-2. Wright Stain: 95% Methanol, Eosin, Methylene Blue. Distilled Water
Figure 6-3. Appearance of a properly stained PBS

3. Evaluation of the Peripheral Blood Smear
A. Focus the stained smear (Fig. 6-3) under LPO and locate an area where cells are
evenly distributed and do not overlap.
B. Transfer to oil immersion objective and examine the RBC paying particular attention
to red cell size, shape and staining reactions. Take note of the presence of inclusion
bodies in the RBC.
C. Report all abnormalities noted.
Figure 6-4. Microscopic appearance of a stained PBS
Figure 6-5. Microscopic appearance of blood cells stained with Wright’s
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ACTIVITY 1 (PBS PREPARATION): ANSWER THE FOLLOWING QUESTIONS TO ENHANCE YOUR
KNOWLEDGE ON PROPER PBS PREPARATION:
1. How do you describe a properly made peripheral blood smear? (5 POINTS)
2. How do you describe a properly stained smear? (5 POINTS)
3. What are the causes of too thin or too thick blood smears? (5 POINTS)
4. What causes too red or too blue staining of a blood film? (5 POINTS)
THE RED BLOOD CELL ANOMALIES
A. VARIATION IN SIZE: ANISOCYTOSIS
Indicators of normal cell size:

i. Cell diameter: 6-8 µm
ii. Mean Corpuscular Volume (MCV): 80-100 fL
iii. Red Cell Distribution Width: 11-14%
1. MICROCYTE
A microcyte (Fig. 6-6R) is a red cell with a diameter of <6 um and an MCV of <80 fL.
The small size is usually associated with failure of hemoglobin synthesis as seen in conditions
like Anemia of Chronic Disease, Thalassemia, Iron Deficiency Anemia and Sideroblastic
Anemia.
I
Figure 6-6. Normocytic (Left) and Microcytic (Right) red blood cells in a smear
2. MACROCYTE
A macrocyte (Fig. 6-7R) has an average diameter >8 um and MCV >100fL. Conditions
such as impaired DNA synthesis, stress erythropoiesis and excess surface membrane cause
the formation of macrocytes. The presence of macrocytes is usually associated with
megaloblastic anemia and liver disease.
Figure 6-7. Normocytic (Left) and Macrocytic (Right) red blood cells in a smear
B. VARIATION IN COLOR (HEMOGLOBIN CONTENT): ANISOCHROMIA
Indicators of normal red cell color:

i. MCHC: 32-36 g/dL
ii. Central pallor: 1/3 of the red cell diameter
1. HYPOCHROMIA
Hypochromic red cells (Fig. 6-8R) have decreased MCHC and present with a central
pallor that is >1/3 of the total cell diameter. Hypochromia is associated with iron deficiency
and thalassemia.
NORMOCHROMIC
Figure 6-8. Normochromic (Left) and Hypochromic (Right) red blood cells in a smear.
2. HYPERCHROMIA
Although this term is not generally accepted in Hematology, it is describing a red
cell with increased MCHC and no central pallor. Spherocytosis and macrocytosis are
conditions associated with hyperchromia.
3. POLYCHROMASIA/POLYCHROMIA
Poly- indicates the presence of more than one color. Polychromasia or polychromia
(Fig. 6-9R)is pertaining to the blue-gray discoloration of a red cell owing to the presence of
RNA remnants inside the red cells that absorbs the alkaline stain. It is an indication of
increased erythropoietic activity associated with hemolytic anemia or physiologic need.
NORMOCHROMIC
Figure 6-9. Normochromic (Left) and Polychromatophilic (Right) red blood cells in a smear
C. VARIATION IN CELL SHAPE: POIKILOCYTOSIS
Indication of a normal shape: biconcave disc-shape
1. Poikilocytes secondary to membrane abnormalities
a. Acanthocytes (Fig. 6-10L) are also known as sour cells or thorn cells. These are
spheroid in shape with 3-12 irregular spikes/spicules caused by abnormal ratios
of membrane lecithin and sphingomyelin or increased ratio of cholesterol to
lecithin. Acanthocytes are seen in end-stage liver disease, alcoholic cirrhosis
with hemolytic anemia, severe hemolytic anemia with cirrhosis and metastatic
liver disease, hepatitis of the new born, malabsorption states, post-
splenectomy states, pyruvate kinase deficiency and abetalipoproteinemia.
Figure 6-10. Acanthocytes (LEFT), Echinocytes (RIGHT)
b. Echinocytes (Fig. 6-10R) or burr cells, crenated cells or sea urchin cells are red
cells with regular 10-30 scalloped short projections. These occur due to
depletion of ATP and exposure to hypertonic salt solution. Sometimes, they also
appear as artifacts in air drying. Clinically, burr cells are associated with uremia,
chronic renal disease, cirrhosis and hepatitis.
c. Target cells or Codocytes (Fig. 6-11L); also termed as target cells or Mexican
hat cells appear as bell or tall hat shaped cells on scanning electron
microscope. The cells show a peripheral rim of hemoglobin surrounded by a
clear area and central hemoglobinized area (resembling a bull’s eye
appearance). Formation of codocytes is due to excess surface membrane to
volume ratio or increased cholesterol and phospholipids. Hemoglobinopathies
SS, CC, DD, EE and disorders such as thalassemias, obstructive liver disease,
post-splenectomy states and iron deficiency anemias cause the formation of
codocytes.
Figure 6-11. Target cells (LEFT); Elliptocytes and Ovalocytes (RIGHT)
d. Elliptocytes (Fig. 6-11R) are rod or cigar shaped cells, that are narrower than
ovalocytes. Defects in the polymerization of hemoglobin that cause defects in
the cytoskeleton or decreased membrane protein band 4.1 lead to a
condition known as Hereditary Elliptocytosis.
e. Ovalocytes (Fig. 6-11R) are egg-like or oval-shaped cells that are wider than
elliptocytes. The change in shape is due to a bipolar arrangement of
hemoglobin or reduction of membrane cholesterol. Disorders exhibiting
ovalocytes include megaloblastic anemia, myelodysplasia or Sickle Cell
Anemia.
f. Spherocytes (Fig. 6-12) are smaller red cells with concentrated hemoglobin
and no visible central pallor. Defective membrane (spectrin deficiency) that
cause the lowest surface area to volume ratio cause the formation of
spherocytes. They are seen in cases of Hereditary Spherocytosis, isoimmune
and autoimmune hemolytic anemia and in severe burns. Banked blood stored
for a long time can also show spherocytes due to storage lesions.
Figure 6-12. Spherocytes (Note absence of central pallor)
g. Stomatocytes (Fig. 6-13) are otherwise known as mouth cells or hydrocytes.

These cells have mouth or slit-like pallor and are bowl-shaped. Stomatocytes
are seen in Hereditary stomatocytosis, alcoholism, cirrhosis, obstructive liver
disease and in Rh null individuals.
Figure 6-13. Stomatocytes
2. Poikilocytes secondary to trauma
a. Schistocytes/Schizocytes (Fig. 6-14) (from the Greek derivation schistos

meaning cloven or schizo that means split) are fragmented red cells varying in
size and shape. There are two (2) variants of schistocytes – the
keratocytes/helmet cells which have hornlike projections and the knizocytes
which are triangular in shape with two (2) pallor areas. Extreme fragmentation
of red cells is caused by presence of fibrin in the blood vessels; altered vessel
walls; or prosthetic heart valves. The occurrence of schistocytes may be
indicative of disseminated intravascular coagulation (DIC); thrombocytopenic
purpura, burns and microangiopathic hemolytic anemia.
Figure 6-14. Schistocytes
b. Dacrocytes (Fig. 6-15) are also known as tear-drop cells. These are pear-
shaped cells with elongated point or tail. The morphological change happens
during squeezing or fragmentation of the red cells during splenic passage.
Associated conditions in the appearance of tear drop cells are myeloid
metaplasia and hypersplenism.
Figure 6-15. Dacrocytes
c. Microspherocytes (Fig. 6-16) or pyropoikilocytes are red blood cells with smaller
diameter that ruptures at a much lower temperature (450C) than a normal red
cell (fragments at 490C). Aside from Hereditary pyropoikilocytosis, severe burns
cause the formation of microspherocytes.
Figure 6-16. Microspherocytes (note small cells without central pallor)
d. Semi-lunar bodies (fig. 6-17), which are known as half-moon/crescent cells, are
large, pale pink staining ghosts of the red cells. They form when the red cell
membrane is disrupted causing the release of its content.
Figure 6-17. Semilunar bodies
3. Poikilocytes secondary to abnormal hemoglobin content
a. Drepanocyte, also known as sickle cells (Fig. 6-18) or menisocytes are cresent-
shaped cells that lack the central pallor. The defect lies in the abnormal
polymerization of deoxygenated hemoglobin due to the presence of an
abnormal hemoglobin compound. This type of poikilocyte is seen in Sickle Cell
Anemia and Hemoglobin SC disease.
Figure 6-18. Sickle cells
D. RED CELL INCLUSIONS
1. Howell-Jolly Bodies
Howell-Jolly bodies (Fig. 6-19) are coarse, round densely stained purple granules
approximately 1-2 um in size that are eccentrically located on the periphery of the red cell
membrane. They may be found singly or in twos in a singular red cell. They are nuclear
remnants that contain DNA and are seen in conditions like megaloblastic anemia,
accelerated erythropoiesis, severe hemolytic process and thalassemia.
Figure 6-19. Howell-Jolly bodies (note dot like inclusions inside red cells)
2. Basophilic Stippling (Fig. 6-20)
Causing punctuate basophilia in the red cell, these are round, dark blue granules that
are uniformly distributed. These are caused by precipitation of ribosomes and RNA in the cell
and are representing impaired erythropoiesis. Fine stippling can be seen in increased
polychromatophilia indicating increased production of red cells while coarse stippling can
be caused by instability of RNA in a young cell which is observed in diseases with impaired
hemoglobin synthesis and severe forms of anemia. Other clinical associations of basophilic
stippling include lead poisoning, pyrimidine-5-nucleotidase deficiency, and heavy metal
poisoning.
Figure 6-20. Basophilic stippling on red cells
3. Cabot Rings
Cabot rings (Fig. 6-21) may present as rings, loops, or figures of eight that are red to
purple in color. They are remnants of the microtubules of the mitotic spindle and are
oftentimes seen in dyserythropoiesis brought about by megaloblastic or severe anemia of
any kind.
Figure 6-21. Cabot rings (note thread-like structure inside red cell)
4. Heinz Bodies (Fig. 6-22, inset)
The precipitation of denatured hemoglobin due to oxidative injury leads to formation
of Heinz bodies. These are inclusions that are 2-3 um in size and deep purple in color found
on the inner surface of the cell membrane. Multiple Heinz bodies can give a pitted golf-ball
appearance to a cell. Only seen supravitally, these are seen in hereditary defects in the
Hexose Monophosohate Shunt, G6PD deficiency, unstable Hemoglobin (Hemoglobin H),
Thalassemia and in patients post-splenectomy.
Figure 6-22. Ruptured red cell (pointed), Heinz bodies (inset)
5. Hb H Inclusions (Fig. 6-23)

Precipitation of Hb H is caused by Alpha-thalassemia otherwise known as Hb H
disease. These are only seen supravitally.
Figure 6-23. Hemoglobin H inclusions
6. Hb CC Crystals
Hb CC crystals (Fig. 6-24) appear as clam shells. They are darkly staining hexagonal
crystals with blunt ends. They manifest in Homozygous C (Hb CC) disease.
Figure 6-24. Hemoglobin CC crystals
7. Hb SC Crystals
Hb SC crystals (Fig. 6-25) are dark-hued crystals of condensed Hb that distort the red
cell membrane. A crystal can create a projection that is often straight with parallel sides and
one blunt end, while the other is a pointed protruding end. They resemble a Washington
monument shape. They are seen in Hb SC disease.
Figure 6-25. Hemoglobin SC crystals
8. Pappenheimer Bodies
Pappenheimer bodies (Fig. 6-26) are also known as siderotic granules. They represent
the unused iron deposits in the body due to defects in heme synthesis. They are 2 to 3 um in
size, irregular blue inclusions that aggregate in small clusters near the periphery of the cell.
Conditions leading to the formation of pappenheimer bodies are Sideroblastic Anemia,
myelodysplastic syndrome, thalassemia, hemolytic anemia and defective erythropoiesis.
Figure 6-26. Pappenheimer bodies (Note dot -like structure inside red cells)
9. Parasites (Fig. 6-27 for sample)

The parasites that can be seen in blood include the hemoflagellates (Leishmania
species and Trypanosoma species); malaria (Plasmodium species) and Babesia species.
Depending on the stages of these parasites, they can be distinctly identified when they are
present inside the red cells.
Figure 6-27. Example of parasite in red cells
E. MISCELLANEOUS
1. Autoagglutination (Fig. 6-28)

This is a phenomenon when red cells aggregate into random clusters or masses due
to exposure to various cell antibodies. Typically, red cells agglutinate in the body’s own
plasma or serum that contains no specific known agglutinins. Associated conditions include
Autoimmune Hemolytic Anemia and Cold Agglutinin Disease such as atypical pneumonia.
Figure 6-28. Autoagglutination of red cells on a smear
2. Rouleaux Formation (Fig. 6-29)

Red cells can have stack of coin arrangement because of the altered zeta potential
among them when plasma proteins are increased. Disorders that lead to hyperproteinemia
like Multiple Myeloma and Waldenstrom’s Macroglobulinemia lead to rouleaux formation.
Figure 6-29. Rouleaux formation
PCQACL Guidelines for Reporting Red Cell Morphology
Requisites:
• A properly made and stained peripheral blood smear that shows an ideal zone
of morphology.
• Examinations done at 40X and 100X magnification.
A. RBC Distribution and Size
1. Agglutination: Report “presence of agglutination”; “cold agglutination present” if

agglutination disappears after warming the sample; or “RBC agglutination present” if
agglutination persists after warming.
2. Rouleaux Formation: Using 40X magnification, rouleaux formation can be reported as:
Slight: intermittent stacks of 4-8 RBCs
Moderate: Frequent stacks of 4-8 RBCs
Marked: Many stacks of RBCs
3. More than 50% microcytosis seen in an oil immersion field (in reference to MCV)
Slight: 76 fL to 79 fL
Moderate: 66 fL to 75 fL
Marked: <66 fL
4. More than 50% macrocytosis in an oil immersion field (in reference to MCV)
Slight: 101 fL to 108 fL
Moderate: 109 fL to 120 fL
Marked: >120 fL
5. Less than 50% microcytes or macrocytes in an oil immersion field (in reference to RDW)
* Report Anisocytosis
Slight: 16 to 18
Moderate: 18 to 22
Marked: >22
B. RBC QUALITATIVE ABNORMALITIES
1. Hypochromia
REPORT MCH MCHC % on PBS
Slight 25-26 pg >30 % 6-15 %
Moderate 21-24 pg >30% 16-30%
Marked <21 pg 25-30% >30#
2. Polychromia
Slight: 2-5%
Moderate: 6-15%
Marked: >15%
3. Large Number of Poikilocytes (Pertaining to the occurrence of a single type of

poikilocyte)
Few: <5%
Moderate: 6-25%
Many: >25%
4. Small Number of poikilocytes (Different types are present, with a total of 6% or more; but
each variant is too small a percentage to quantitate separately)
Slight: 6-10%
Moderate: 11-15%
Marked: >15%
C. DIAGNOSTIC ABNORMALITIES and INCLUSIONS
1. Basophilic Stippling
Slight: 1-5%
Moderate: 6-10%
Marked: >10%
2. Howell-Jolly and Pappenheimer Bodies

Few: 1-2%
Moderate: 3-5%
Many: >5%
3. Nucleated RBCs
a. Report number/100 WBCs or 1000 RBCs
b. If >10 nRBCs/100 WBCs or 1000 RBCs, perform WBC correction
4. Malarial Parasites
Report presence, identifying the genus, species and stage.
UNIT 2: WHITE CELL ANOMALIES
Owing to the fact that white blood cells are a heterogenous population, anomalies
of white blood cells can be classified according to the type of cell, cell parts affected and
function.
A. NUCLEAR ABNORMALITIES
1. Hyposegmentation
Hyposegmentation (Fig. 6-30) is a benign anomaly of neutrophils where the nucleus
fails to segment properly thus the cell presents with a bilobed nuclei (Dumbbell-shaped/
Spectacle-shaped/ Peanut-shaped/ “Pince-nez”). Conditions associated with this are:
o Inherited: Pelger-Huet Anomaly (Autosomal dominant)
o Acquired: Pseudo-Pelger Huet Anomaly; Myelofibrosis
Figure 6-30. Hyposegmentation in mature neutrophils
2. Hypersegmentation (Fig. 6-31)

It is another abnormality in the maturation of the neutrophils (abnormality in DNA
synthesis) that leads to the presence of 6 or more lobed nucleus. Associated conditions in
hypersegmentation are:
o Inherited: Undritz Anomaly (Autosomal dominant)
o Acquired: Megaloblastic anemia
Figure 6-31. Hypersegmentation in neutrophils
3. Barr body (Sex chromatin)
The appendage (Fig. 6-32) seen in the nuclear material represents the second X
chromosome in females (may be seen in 2-3% of neutrophils in females). The barr body is
NOT FOUND IN NORMAL MALES. It is a small, well-defined, round projection of nuclear
chromatin that is connected to the nucleus of the neutrophil by a single, fine strand of
chromatin.
Figure 6-32. Barr bodies in neutrophils

B. CYTOPLASMIC ABNORMALITIES
1. Alder-Reilly Bodies
Alder Reilly bodies (Fig. 6-33) are large purple-black coarse cytoplasmic granules.
They are accumulations of degraded mucopolysaccharides. They may be found in all
leukocytes in cases of:
o Alder-Reilly Anomaly (Autosomal recessive)
o Mucopolysaccharidoses
o Hurler’s syndrome
o Hunter’s syndrome
Since they may resemble toxic granules, Cetyl Trimethyl Ammonium Bromide (CTAB)
Test is used to differentiate them. The occurrence of white turbidity is indicative of Alder Reilly
bodies.
Figure 6-33. Alder-Reilly bodies
2. Auer Rods
They are pink or red rod-shaped cytoplasmic structures (Fig. 6-34) that are formed
from the fusion of primary granules. They are normally found in the younger myeloid
precursors thus are peroxidase positive. When seen in mature cells, they are associated with
AML or AMML.
Figure 6-34. Numerous Auer Rods in Immature Cell of the Myeloid Series
3. Chediak-Higashi granules (Fig. 6-35)

These appear as giant red, blue to grayish round inclusions that are deficient in
enzymes for phagocytosis. The giant lysosomal granules are seen in lymphocyte, neutrophil,
and monocyte and are peroxidase and Sudan Black B positive. They are seen in Chediak-
Higashi Syndrome.
Figure 6-35. Chediak Higashi Inclusions in Neutrophils
4. Dohle Bodies (Fig. 6-36)
Also known as Amato Bodies, these are single or multiple blue cytoplasmic inclusions
in the neutrophil that are aggregates of free ribosomes or rough endoplasmic reticulum.
They are often confused with May-Hegglin anomaly (the leukocyte inclusions in May-Hegglin
anomaly are composed of precipitated myosin heavy chains). They are seen in severe
infections, toxic states and in burns.
Figure 6-36. Dohle body in Neutrophils
5. Toxic granules
These are large purple to black azurophilic granules thought to be primary granules
showing increased ALP activity. They are often present with Dohle bodies and toxic vacuoles
and are seen in cases of:
o Infections
o Toxic states
o Burns
o Malignancy
o Chemical poisoning
6. Toxic vacuoles (Fig. 6-37)

These vacuoles are large empty white areas
within cytoplasm that represent end-stage
phagocytosis. They are commonly associated with:
o Septicemia
o Severe infections
o Toxic states
Figure 6-37. Toxic vacuolation

in neutrophils
C. ABNORMALITIES OF CELLS EXHIBITING PHAGOCYTOSIS
1. LE cell
An LE cell (Fig. 6-38) is a neutrophil with large purple homogenous round inclusion with
nucleus wrapped around; appear smooth and evenly stained. It is seen in autoimmune
disorders such as Lupus erythematosus.
Figure 6-38. LE Cell
2. Tart Cell (Fig. 6-39)

It is a monocyte with ingested lymphocyte; and appears rough & unevenly stained.
Figure 6-39. Tart cell
D. FUNCTION ABNORMALITIES
1. Job syndrome
In Job’s syndrome, neutrophils exhibit normal random activity (chemokinesis) but
abnormal directional activity (chemotaxis).
NOTE:
Chemokinesis: Random locomotion
Chemotaxis: Directed locomotion brought about by CHEMOTAXINS (chemotactic
factors such as endotoxins and other bacterial products, cytokines, and
lymphokines)
Diapedesis: Locomotion through unruptured walls of the blood vessels
2. Lazy Leukocyte Syndrome

In LLS, neutrophils have abnormal random and directional activity
3. Chronic granulomatous disease

In CGD, there is inability of phagocytes to kill ingested microorganisms due to
impaired NADPH oxidase/ Respiratory burst. The diagnostic test for CGD is Nitroblue
tetrazolium dye test.
4. Leukocyte Adhesion Disorder- I (LAD-I)

This is caused by decreased or truncated β2 integrin, needed for neutrophil adhesion
to endothelial cells and recognition of bacteria that leads to:
o Recurrent infections
o Neutrophilia
o Lymphadenopathy
o Splenomegaly
o Skin lesions
1. Leukocyte Adhesion Disorder-II (LAD-II)

LAD-II is caused by decreased amount or function of selectin ligands and defective
leukocyte recruitment. Clinical findings in LAD-II include:
o Physical growth retardation
o Coarse face and/ or other physical deformities
o Neurological defects
o Recurring infections
o Absent blood group H antigen
2. Leukocyte Adhesion Disorder-III (LAD-III)

This is brought about by defective protein Kindlin-3, needed for β integrin activation
and leukocyte rolling. Failed response to external signals that would normally result in
leukocyte activation. In this disease, the clinical findings are:
o Recurrent bacterial and fungal infections (less severe than LAD-I)
o Decreased platelet GPIIbβ3 leading to bleeding
E. ABNORMALITIES ASSOCIATED WITH LYMPHOCYTES
1. Atypical lymphocytes (Fig. 6-40)

They are also known as reactive lymphocytes, variant lymphocytes, transformed
lymphocytes, and leukocytoid lymphocytes. They can be referred to as DOWNEY CELLS
(Classification by Dr. Hal Downey) of different types:
o Type I
▪ Turk’s Irritation cells/ Plasmacytoid lymphocytes
▪ Characterized with a large block of chromatin
o Type II
▪ IM cell
▪ Characterized by a round mass of chromatin; “BALLERINA SKIRT”
appearance
▪ Seen in Infectious Mononucleosis
• Causative agent: Epstein-Barr virus
• Characterized by lymphocytosis often mistaken as
monocytosis (hence the name mononucleosis)
• The atypical lymphocytes are T lymphocytes reacting to
EBV-infected B lymphocytes
o Type III
▪ Vacoulated, “Swiss cheese” appearance, “Moth-eaten”
appearance
Figure 6-40. Classic Presentation of Atypical Lymphocytes in a PBS
2. Basket cell/ Smudge cell (Fig. 6-41)
These are white blood cells that have degenerated nucleus or ruptured cell in form
of smudge or basket. Basket cells are diagnostic of Chronic Lymphocytic Leukemia.
Figure 6-41. Basket cells

3. Hairy cell
Hairy cells (Fig. 6-42) are B lymphocytes with hair like cytoplasmic projections
surrounding the nucleus. Seen in Hairy cell leukemia (associated with Human T-lymphotropic
virus Type II), they stain positive with tartrate resistant acid phosphatase (TRAP).
Figure 6-42. Hairy cells
4. Sezary cell
Sezary cell (Fig. 6-43) is a lymphocyte with T cell characteristics with nucleus that is
grooved and have brain like convolutions (“cerebri” form). Associated conditions where
Sezary cells are seen include:
o Sezary syndrome (leukemic phase)
o Mycosis fungoides (leukemic phase)
o Cutaneous T-cell lymphoma
Figure 6-43. Sezary cells
F. ABNORMALITIES ASSOCIATED WITH PLASMA CELLS
1. Flame Cell (Fig. 6-44)

It is a plasma cell with red to pink cytoplasm associated with increase in
immunoglobulin (IgA). It is observed in multiple myeloma.
Figure 6-44. Flame cells
2. Russell Bodies (Fig. 6-45)
These are individual globules of immunoglobulins seen in plasma cells.
Figure 6-45. Russell bodies
3. Grape Cell/ Berry Cell/ Morula Cell/ Mott Cell (Fig. 6-46)
These are plasma cell that contains vacuoles and large protein globules (appearing
like grapes). Sometimes, it occurs as the accumulation of Russell bodies and is observed in
multiple myeloma and reactive states.
Figure 6-46. Grape cells
4. Dutcher’s Bodies (Fig. 6-47)
These bodies are intranuclear protein inclusions occurring in the plasma cell.
Figure 6-47. Dutcher’s bodies
G. MONOCYTE/ MACROPHAGE LYSOSOMAL STORAGE DISORDERS

Type Deficient Enzyme Accumulation of: Morphologic
Appearance
Lipid Storage Diseases
Gaucher β-glucocerebrosidase Accumulation of Wrinkled/ Crumpled
Disease Glucocerebroside Cytoplasm
“Cat-Scratch”
Cytoplasm
Others: Clinical Triad

used in Diagnosis
Hepatomegaly
Gaucher cells in
BM
Increased serum
phosphatase
Niemann- Accumulation of
Sphingomyelinase Foamy cytoplasm
Pick Disease sphingomyelin
Fabry
α-galactosidase Ceramide trihexose
Disease
Tay-Sachs
Hexosaminidase A GM2 ganglioside Vacuolated cytoplasm
disease
Sandhoff Rodak: Glycolipid &
disease Hexosaminidase A ganglioside Vacuolated cytoplasm
Hexosaminidase A & B
Sea Blue Unknown Unknown Blue-green cytoplasm
Histiocytes
Type Name Deficient Enzyme Accumulated

Substance
Mucopolysaccharidosis
MPS I- Hurler Syndrome α-l-iduronidase Dermatan sulfate,
Severe heparan sulfate
MPS I- Scheie Syndrome α-l-iduronidase Dermatan sulfate,
Attenuated heparan sulfate
MPS II- Hunter Syndrome Iduronate sulfatase Dermatan sulfate,
Severe heparan sulfate
MPS III Sanfilippo Syndrome Heparan-N-sulfate Heparan sulfate
Type A
Sanfilippo Syndrome a-N- Heparan sulfate
Type B acetylglucosaminidase
Sanfilippo Symdrome Acetyl–coenzyme A:a- Heparan sulfate
Type C glucosaminide
N-acetyltransferase
MPS IV Morquio syndrome Galactose-6-sulfatase Keratan sulfate,
Type A chondroitin-6-sulfate
Morquio syndrome β-Galactosidase Keratan sulfate
Type B
QUIZ (ANOMALIES):
A. Write a PBS report on the following results using the PCQACL Guidelines for reporting RBC
morphology (2 points each)
Example:
1. Majority of cells are macrocytic, MCV is 120 fL, 29 polychromatic red cells seen.
PBS Report: Smear shows marked macrocytosis with marked polychromia.
1. More than half of the red cell population are macrocytic, MCV is 115fL.
2. MCH is 20 pg, RDW is 25
3. MCV is 90 fL, there are 7 polychromatophilic red cells in 10 OIFs.
4. MCV is 60 fL, MCH is 22 pg
5. MCH is 20 pg, RDW is 20, majority of cells are microcytes with an MCV of 60 fL, and
25 echinocytes are noted.
6. MCH is 23 pg, RDW is 19, majority of cells are microcytes with an MCV of 78 fL, and
the presence of 2 target cells, 1 teardrop cell, 2 burr cells and 2 helmet cells
7. MCH is 23 pg, RDW is 20, majority of cells are microcytes with an MCV of 79 fL and
18 semi-lunar bodies.
8. MCV is 90 fL and MCH is 30 pg.
9. MCV is 95 fL, MCH is 30 pg, there are 8 nucleated red cells seen in 10 OIFs.
10. More than half of the red cell population are microcytic, MCV is 62 Fl
B. HEADINGS: Classify accordingly. (20 points)

A. Secondary to membrane abnormality
B. Secondary to trauma
C. Abnormal Hemoglobin content
D. Inclusions
E. Anisocyte
1. Anulocyte 6. Target Cell

2. Polychromasia 7. Sickle Cell
3. Spherocyte 8. Dacrocyte
4. Ovalocyte 9. Microspherocyte
5. Stomatocyte 10. Burr Cell
A. Cytoplasmic change
B. Nuclear Alteration
C. Impaired Granulocyte Function
D. Inherited Disorder of Immune Leukocytes
E. Defective Killing of microorganism
1. May-Hegglin Anomaly 6. Pelger-Huet Anomaly

2. Chediak-Higashi Syndrome 7. Pyknosis
3. Lazy Leukocyte Syndrome 8. Toxic Granulation
4. Ataxia Telangectasia 9. Macropolycyte
5. Downey Cell 10. Alder-Reilly bodies
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M06 - Blood Cell Anomalies

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M06 - Blood Cell Anomalies

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MODULE 6

BLOOD CELL ANOMALIES

1. Recall the normal morphologic presentations of erythrocytes and leukocytes.

UNIT 1: RED CELL ANOMALIES

Recall the appearance of a normal red cells. Provide the

INDICES NORMAL VALUES

Name: _______________________________ Rating: _______________

1. Types of anisocytes compared to a normocyte.

QUESTIONS FOR RESEARCH:

Figure 6-1. Peripheral Blood Smear Preparation

Figure 6-3. Appearance of a properly stained PBS

Figure 6-4. Microscopic appearance of a stained PBS

Figure 6-5. Microscopic appearance of blood cells stained with Wright’s

1. How do you describe a properly made peripheral blood smear? (5 POINTS)

2. How do you describe a properly stained smear? (5 POINTS)

Indicators of normal cell size:

Indicators of normal red cell color:

Indication of a normal shape: biconcave disc-shape

1. Poikilocytes secondary to membrane abnormalities

Figure 6-10. Acanthocytes (LEFT), Echinocytes (RIGHT)

Figure 6-11. Target cells (LEFT); Elliptocytes and Ovalocytes (RIGHT)

Figure 6-12. Spherocytes (Note absence of central pallor)

g. Stomatocytes (Fig. 6-13) are otherwise known as mouth cells or hydrocytes.

Figure 6-13. Stomatocytes

a. Schistocytes/Schizocytes (Fig. 6-14) (from the Greek derivation schistos

Figure 6-14. Schistocytes

Figure 6-15. Dacrocytes

Figure 6-16. Microspherocytes (note small cells without central pallor)

Figure 6-17. Semilunar bodies

Figure 6-18. Sickle cells

D. RED CELL INCLUSIONS

Figure 6-20. Basophilic stippling on red cells

Figure 6-22. Ruptured red cell (pointed), Heinz bodies (inset)

5. Hb H Inclusions (Fig. 6-23)

Figure 6-23. Hemoglobin H inclusions

Figure 6-24. Hemoglobin CC crystals

Figure 6-25. Hemoglobin SC crystals

9. Parasites (Fig. 6-27 for sample)

Figure 6-27. Example of parasite in red cells

1. Autoagglutination (Fig. 6-28)

Figure 6-28. Autoagglutination of red cells on a smear

2. Rouleaux Formation (Fig. 6-29)

Figure 6-29. Rouleaux formation

A. RBC Distribution and Size

1. Agglutination: Report “presence of agglutination”; “cold agglutination present” if

B. RBC QUALITATIVE ABNORMALITIES

3. Large Number of Poikilocytes (Pertaining to the occurrence of a single type of

C. DIAGNOSTIC ABNORMALITIES and INCLUSIONS

2. Howell-Jolly and Pappenheimer Bodies

Figure 6-30. Hyposegmentation in mature neutrophils

2. Hypersegmentation (Fig. 6-31)

Figure 6-31. Hypersegmentation in neutrophils

Figure 6-32. Barr bodies in neutrophils

Figure 6-33. Alder-Reilly bodies

3. Chediak-Higashi granules (Fig. 6-35)

Figure 6-35. Chediak Higashi Inclusions in Neutrophils

Figure 6-36. Dohle body in Neutrophils

6. Toxic vacuoles (Fig. 6-37)

Figure 6-37. Toxic vacuolation

Figure 6-38. LE Cell

2. Tart Cell (Fig. 6-39)

Figure 6-39. Tart cell

2. Lazy Leukocyte Syndrome

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