MLS 3A – RBC ANOMALIES – fRMT2022
NAME AND PICTURE OTHER NAME AND DESCRIPTION OF THE
CHARACTERISTICS OF THE ANOMALIES
ACANTHOCYTE, ECHINOCYTE Echinocytes
● “Burr cells”
● Smaller in size compared to
acanthocytes
● Uniform, evenly-spaced blunt
projections
● Often seen as an ARTIFACT - when
anticoagulated blood is left standing for
too long
● Become crenated due to osmolarity
CODOCYTE, LEPTOCYTE Codocyte
● “Target cells” or “Bull’s eye”
● “Mexican Hat cells”
● Dark center surrounded by a white ring
followed by a dark outer second ring
○ contains a band of hemoglobin
● Can be compared to an archery target
● In vivo, the codocyte is a bell-shaped or
cup-shaped cell
○ KODON (Greek) = BELL
● assumes a "target" configuration only
when processed to obtain a blood film
Leptocyte
● “Wafer cells”
● “Folded cells”
● Thin RBC with increased membrane and
decreased amount of volume
● Wafer-thin and generally large in
diameter
DISEASE ASSOCIATION
Pyruvate Kinase Deficiency
● ATP Depletion
● Defect in the conversion of
phosphoenolpyruvate to
pyruvate = decrease ATP
production
● Decreased ATP = Cells
dehydrate = Echinocytes
Uremia
● Increased urea in the blood
causes the deformation of
the RBC
Liver Disease
● Lecithin—cholesterol
acyltransferase (LCAT) activity
may be decreased in
obstructive liver disease.
● Decreased enzymatic activity
increases the cholesterol to
phospholipid ratio, producing
an absolute increase in
surface area of the red blood
cell membranes.
Hemoglobinopathies
● Typically, the hemoglobin is
reduced and non-functional,
and it causes red blood cells
to have a shortened lifespan.
Thalassemia
● DNA mutations in cells that
are responsible for producing
hemoglobin.
● Decrease in the cell volume
and increase in surface area
resulting in a relatively excess
membrane which will result
MLS 3A – RBC ANOMALIES – fRMT2022
● The central spot is not completely in the formation of the target
detached from the peripheral ring cells.

○ the pallor is in a C shape rather

than a full ring

● Some appear folded or concave

● seen in thalassemia and with

Asplenia
obstructive liver disease
● Absence of the normal
functioning of the spleen.

● Any abnormally shaped red

blood cells normally get
removed by the spleen.
ELLIPTOCYTE cigar shaped ● Hereditary Elliptocytosis

● aka “Ovalocyte” ● caused by membrane

integrity defect
○ Cigar-shaped
○ EPB41 gene - Band
○ Pencil
4.1
○ Rod
○ SPTA1 gene - alpha
● Elliptical and monochromatic cells seen spectrin
in 1% of RBC
○ SPTB gene - beta
spectrin

● Treatment: Splenectomy

● Hereditary Ovalocytosis

○ nucleotide deletion in
SLC4A1 gene - Band 3

○ associated with
malarial resistance -
hard to penetrate rbc
membrane

● Treatment: Not necessary

OVAL MACROCYTE “Macroovalocyte” ● Megaloblastic anemia

● Appears like a large oval RBC ○ characterized by

having oval
● Has an egg shape appearance
macrocytes
● Almost no central pallor observed
○ low production of red
● Increased thickness blood cell

CAUSED BY
MLS 3A – RBC ANOMALIES – fRMT2022
○ Folate deficiency

○ Vitamin B12
deficiency
SPHEROCYTE ● Lacks central pallor ● Hereditary Spherocytosis

● Appears darker and smaller than the ● Immune Hemolytic Anemia

normal normocytic red blood cell.
● Extensive burns
● Defect in the erythrocyte membrane.

● Decreased surface area to volume ratio.

● Extremely compat, round shape

STOMATOCYTE Also called as “hydrocytes” ● Artifact

- seen as an artifact of a drying

blood smear, but only be
Are erythrocytes with a slit-like central pallor,
seen on some areas on the
giving them the appearance of "coffee beans"
periphery of the blood smear.
or "kissing lips"
● Hereditary Stomatocytosis

- Presents with various degrees

of hemolytic anemia and
abnormal red blood cell (RBC)
morphology

- Overhydrated Hereditary
Stomatocytosis
(Hydrocytosis): abnormally
increased cation influx results
in swollen erythrocytes,
hemolysis, and stomatocytes

- Dehydrated Hereditary
Stomatocytosis
(Xerocytosis): net loss of
cations and water results

● Rh Null Syndrome

- Also known as Rh null

syndrome

- Lacking all Rh antigens that

maintain the integrity of the
RBC membrane

● Acquired Stomatocytosis

- Seen in chronic liver disease

(most often due to
alcoholism) or acute alcohol
MLS 3A – RBC ANOMALIES – fRMT2022
intoxication

- Due to a reduction in RBC

membrane surface area
rather than an increase in
RBC volume

DREPANOCYTE Other names: Sickle cell Anemia

•Sickle cell •Most common type of SCD

•Menisocyte •When person inherit two sickle cell

gene (SS)
•Crescent cell
•No normal adult hemoglobin (Hb A)
•Thin, dense, elongated
due to abnormal beta-globin chain.
•pointed at each end;
•Impaired ability to carry oxygen
•may be curved
•Characterized by chronic hemolytic
•normocytic or normochromic anemia

•Poikilocytosis and anisocytosis Sickle Cell-Beta Thalassemia

•Compound heterozygosity for Hb
•Presence of long, curved cell with a S and b-thalassemia
point at each end – diagnostic cell •B-thalassemia – deficiency in b-
(sickle cell) globin production

•Clinical syndrome resembling that

of mild or moderate sickle cell
anemia.

•Severity based on b-chain

production of b-thalassemia gene:
•Hb S–B°-thal – complete loss of
beta globin

•Hb S–B1-thal – partial loss of beta

globin

SCHISTOCYTE, KERATOCYTE, Schistocyte ● Macroangiopathic hemolytic anemia

BLISTER CELL
Other names: ● Microangiopathic hemolytic anemia

● Schizocyte, ● Extensive burns

● Erythrocyte Fragments

● Microspherocytes
MLS 3A – RBC ANOMALIES – fRMT2022
Causes:

● Certain genetically determined disorder

● Acquired disorders of megaloblastic

erythropoiesis

● Consequence of mechanical dress

● Result of direct thermal injury

Characteristics

● No central palor

● Erythrocyte fragments

● Ruptures in peripheral

Blister Cell

● Hemi-Ghost (Half ghost)

● Pruse Cell

● Pre-Keratocyte

Characteristics:

● Cells with pseudovacuoles are called

“blister” cells or pre-keratocytes. This
cell has freed itself from a fibrin strand,
and when the vacuole bursts, one or
more projections may be visible.
Survival time in circulation for these.

● Keratocyte is formed when Blister Cells

ruptures

Keratocyte

● Horn Cell

● Helmet Cell

● Bite Cell

Characteristics:

●
MLS 3A – RBC ANOMALIES – fRMT2022

DACRYOCYTE

● Red blood cell with a single pointed ● Primary myelofibrosis

extension, resembling a teardrop
● Myelophthisic anemia
● RBC is squeezed in a bone marrow or
● Thalassemia
spleen in a connective tissue
● Megaloblastic anemia
● Also known as TEARDROP CELL

● Dakryon- Greek “tear”

● Cyte- “cell”

SIDEROCYTE/SIDEROBLAST

HOWELL – JOLLY BODIES Howell-Jolly Body Hemolytic Anemia

● By William Henry Howell and Justin ● RBCs are destroyed faster

Marie Jolly. than they are made.

● Dark blue-purple, fine or coarse ● Normocytic; High Retic

granules.

● Usually 1-2 um in size.

Thalassemia
● Usually one per cell; occasionally
● Defective globin chain
multiple
synthesis.
● Composed of: DNA (nuclear fragment)
● Microcytic
● Formed during the pinching process of
pyrenocyte in orthochromic normoblast.
Hyposplenism

Asplenia

Postsplenectomy

Megaloblastic anemia

Myelodysplastic anemia
CABOT RINGS ● By Richard Clarke Cabot in 1903. Megaloblastic anemia

● Red-reddish purple rings, figure-of- Conditions that impair synthesis of

eights, loop-shaped. DNA, such as folate and VitB12
deficiency and myelodysplasia.
● Either double or multiple rings.
MLS 3A – RBC ANOMALIES – fRMT2022
● Represent remnants of microtubules
from the mitotic spindle.
Myelodysplastic anemia
● Or remnants from abnormal histone
Group of cancers in which blood cells
biosynthesis.
in the bone marrow do not mature.
● Presence: abnormal erythropoiesis

PAPPENHEIMER BODIES Sideroblastic Anemia

Other name: Siderotic granules a.Hereditary

● 2-3 um irregular basophilic inclusions
● aggregate in small clusters
-X linked gene- ALAS2 gene-
important for coding ALA-synthaseà
without this, it leads to the
accumulation if iron, mainly affects
boys
-autosomal
b.Acquired

● found near the periphery with Wright’s Ring Sideroblast-hallmark for

Siderobastic anemia
stain Hemoglobinopathies

● light-dark blue granules

A result from genetic mutation in one
or more genes that affect hemoglobin
molecules.

● Prussian blue is used to stain the

Thalassemia

A group of inherited disorders

inclusion of the cell which is the iron. wherein genetic mutations cause the
The iron takes up the Prussian blue and reduction and prevent the production
stains dark blue.
of globin chain/s.

● iron inclusions Megaloblastic Anemia

Due to: Deficiency in Vitamin B12 and

Folic Acid, intake of drugs that
interferes DNA synthesis

Myelodysplastic Syndrome

Hyposplenism

Post-splenectomy

HEINZ BODIES, BITE CELL “Heinz Bodies” G6PD DEFICIENCY | EXPOSURE TO

OXIDANTS| HEMOLYTIC ANEMIA
“Heinz-Erlich Bodies”
● G6PD is an enzyme used in
● Discovered by Dr. Robert Heinz in 1890 the pentose phosphate (or
● When viewed under a microscope HMP Shunt) pathway
MLS 3A – RBC ANOMALIES – fRMT2022
during blood testing, they’re visible as ● In G6PD deficiency, the loss
abnormal clumps that extend from the of the G6PD enzyme has
red blood cells. serious consequences that
increase oxidative stress. (↓
● Distinct characteristic. indicates
NADPH)
oxidative damage to the hemoglobin in
red blood cells. ○ Oxidation of sulfhydryl
group of protein inside
○ Note: Deep blue-purple
the RBC causes
irregular-shaped inclusions 2 to
denaturation and
3 um
formation of insoluble
○ Found on RBC inner surface of masses, Heinz bodies
the membrane
○ Attachment to RBC
membrane →
Rigidity/damage
“BITE CELLS”
○ Macrophage detects and
“Degmacytes”
removes damaged
● Distinct characteristic. an abnormally portions of the cell, the
shaped mature red blood cell with one damaged cell
or more semicircular portions removed membrane, and
from the cell margin. denatured hemoglobin
→ bite cells
● it results from the removal of denatured
Hemoglobin by macrophages of the ● Exposure to toxins or
spleen. oxidants can cause increased
oxidative stress (primaquine,
● a result from processes of oxidative
dapsone, quinidine, etc)
hemolysis

● Severe damage to cell leads

to lysis resulting in hemolytic
anemia

UNSTABLE HEMOGLOBIN

● It is inherited as autosomal
dominant disorders

● Result from genetic

mutations to globin genes
creating hemoglobin
products that precipitate in
vivo, producing Heinz bodies
and causing hemolytic
anemia.

○ Heinz bodies attach

MLS 3A – RBC ANOMALIES – fRMT2022
to cell membranes
causing clustering of
band 3 and
macrophage
activation.

○ Hb Koln - most
prevalent
BASOPHILIC STIPPLING “Punctate Basophilia” ● Lead Poisoning - most common.
Inhibition of Ribonuclease
The presence of numerous basophilic granules
(RNase)
that are dispersed through the cytoplasm of
● Thalassemia: Alpha and Beta
erythrocytes in a peripheral blood smear.
thalassemia -decrease production
Appearance is due to the defect or disrupt of healthy RBCs and Hgb
erythropoiesis ● Hemolytic Anemia (Sickle cell) -
RBCs rapidly destroyed
CHARACTERISTICS ● Megaloblastic Anemia - RBC
● Looks like “Sprinkled Donuts” larger than normal. Deficiencies
● Fine or coarse in Vit B12 and folic acid (folate)
● Deep blue to purple staining inclusion will lead to defective DNA
● Much smaller than Howell-Jolly bodies synthesis
● Irregularly shaped ● Myelodysplastic Syndrome
(MDS) - poorly formed RBCs and
doesn’t work properly

HEMOGLOBIN C CRYSTAL Hemoglobin C Crystals Hemoglobin C Crystals

- no other names -Hb C Disease

- Reddish Hexagonal crystal of dense -caused due to mutation in the

hemoglobin formed within the RBC beta-globin chain in which glutamate
membrane (acidic) is replaced by lysine (basic) in
the sixth position of the beta-globin
- described as a “gold bar,” or
chain
“Washington monument.”
-Hereditary
- Typical of compound heterozygous
hemoglobin SC disease

- crystals form as deoxyhemoglobin S and

C polymerize

TESTS: hemoglobin electrophoresis or high-

performance liquid chromatography (HPLC),
peripheral blood smear

HEMOGLOBIN SC CRYSTAL
Hemoglobin SC Crystals

- no other names
MLS 3A – RBC ANOMALIES – fRMT2022
- Fingerlike or quartz-like crystal of dense
hemoglobin protruding from the RBC
membrane
- Irregular reddish cytoplasmic red blood
cell crystal described as a “glove” or
“pistol.”
Tests: Hemoglobin solubility screening test
HEMOGLOBIN H BODIES Alpha thalassemia intermedia
● Hemoglobin H disease (HbH) is a form
of alpha thalassemia in which
moderately severe anemia develops due Hb Bart Hydrops Fetalis Syndrome
to reduced formation of alpha globin
chains
● RBC are microcytic and hypochromic
with marked poikilocytosis
● Golf ball or raspberry inclusion
● Hemoglobin H inclusion seen as faint
blue inclusion
● Stained with Brilliant Cresyl blue or
Methylene Blue
● RBCs with Hb H display fine, evenly
distributed, granular inclusion.
Hemoglobin SC Crystals
- Hb SC Disease
- Other names: Sickle cell -
hemoglobin C disease; HbSC
disease; Sickle cell-
hemoglobin C disease
syndrome
- caused by the mutation at
position 6, glutamic acid is
replaced by valine (Hb S) on
one b-globin chain and by
lysine (Hb C) on the other b-
globin chain
- compound heterozygosity
● Hb H disease is characterized
by mild to moderate chronic
hemolytic anemia
● Have no functioning α chain
genes
● Hb Bart's has high oxygen
affinity so cannot carry
oxygen to tissues
● Baby born with hydrops
fetalis, which is edema and
ascites caused by
accumulation serous fluid in
fetal tissues as result of
severe anemia
● The fetus is severely anemic,
which leads to cardiac failure
and edema in the fetal
subcutaneous tissues
● Hepatosplenomegaly
● Cardiomegaly
Test:
- Blood Test
- Hemoglobin Electrophoresis