RBC ABNORMALITIES

ANISOCYTOSIS (VARIATION IN SIZE)

⎯ it talks about the alterations or change of size of our red blood cells. there are different
changes that our red blood cells would tend to look like when we see it in the peripheral blood
smear. What are the causes of why do we acquired this?
⎯ A normal erythrocyte has an average diameter of 7.2 mm with a usual variation of 6.8 to 7.5 mm
The extreme size limits are generally considered to be 6.2 to 8.2 mm. This normal size is referred
to as NORMOCYTIC. Erythrocyte may be ither larger than normal (macrocytic) or smaller than
normal (microcytic). Macrocytic erythrocytes exceed the 8.2 mm diameter limit, whereas
microcytic erythrocytes are smaller than the average 6.2 mm diameter.
⎯ The size of red blood cells depends on the protocol of the laboratory.
⎯ The general term used in hematology to denote an increased variation in cell size is
ANISOCYTOSIS. We cannot come up with the term anisocytosis if we only see 1 large
size of red blood cell. We can only term it if there are more than 3 red blood cells that are
different in size may it be big or small. Furthermore, when we see 1 red blood cell that is
different in size is pwedeng dahilan nito ay yung pagkakasmear mo or yung pag spread
mo.
⎯ This term is non-specific because it does not indicate the type of variation that is present.
Anisocytosis is prominent in severe anemias. For example, we already know that the red
blood cell is microcytic but take note that is non-specific that is why we need to perform
other laboratory test to aid our testing and our accurate result. Anisocytosis is prominent
in severe anemias, since it is non-specific, what if yung patient kakaacquire niya palang
yung anemia (acute anemia) and at the same time kaka accumulate niya yung anemia, so
the problem here is we cannot detect the anisocytosis on patient blood smear that is why
we need to perform another laboratory test. Usually in anemia we do not only rely or
depend in the change of size of the red blood cell but we can also rely on other factors
such as hemoglobin, red blood cell count, the complete blood count, diuretics,
hematocrit, and etc. It depends in the protocol of the laboratory.
WE HAVE THREE (3) CATEGORIES OF AANOSOCYTOSIS:
**The reference range of MCV is 100***
1. Microcytic – less than 80.
2. Normocytic – lies between 80-100.
3. Macrocytic – beyond 100.
The basis for identifying these three is the MEAN CELL VOLUME (MCV) as an indicator whether our
red blood cell is a microcytic, macrocytic, and normocytic.
NORMAL RED BLOOD CELL

⎯ Biconcave disc shape

⎯ Salmon pink (the pinkish is from the hemoglobin (Hb)
 ⎯ 7.0 um (7-8 um)
⎯ Has an increased life span due to enzyme (hexose monophosphate pathway – would help
increase the life span of the rbc)
⎯ Anucleated (walang nucleus)
⎯ Is not rigid and has no inclusions (red blood cells must be deformable and has no fragment
seen inside the red blood cell)
VARIATIONS IN RED BLOOD CELL MORPHOLOGY

⎯ In many disorders or disease states, erythrocytes may demonstrate variations in appearance or

morphology as the result of pathologic conditions.
⎯ Variations in red blood cell morphology is not NORMAL. Meron tayong red cell morphology
na nagcacause sa ating pag blood smear. Usually, normal yung red blood cell
morphology but when we examine under the microscope there is a spikey end because
the red blood cell morphology is not good. Konting touch lang is nagbabago na agad
yung morphology niya. If the red blood cell is not stable on its morpholy paiba-iba it
means that it is PATHOLOGIC.
The variations from normal can be classifies as
1. Variation in size - anisocytosis
2. Variation in shape -
3. Variation in color –
4. Inclusions in the erythrocyte
5. Alterations in the erythrocyte distribution on a peripheral blood smear.
ANISOCYTOSIS: VARIATION IN SIZE

⎯ RDW (RED BLOOD CELL DIAMETER WIDTH) – numerical expressions that correlates with
the degree of anisocytosis. It is not similar with MCV because in MCV it measures of what
the volume or the capacity of the red blood cell in the cytoplasm while in RDW it talks
about what degree the variation of size of the red blood cell. For example, there are 3 red
blood cells that are different in size compared to the other RBCs in the peripheral blood
smear, so mababa lang yung degree of anisocytosis compared to the 100 red blood cells
na magkakaiba yung size to that of the other red blood cells in the PBS so mas mataas
yung degree ng anisocytosis doon.
⎯ RDW can be reported and present in our COMPLETE BLOOD COUNT in the AUTOMATED
METHOD wherein in automated method ipapasok lang natin si EDTA tube then bahala na
si machine to test the sample.
⎯ NV: 11.5-14.5%
⎯ Normocytic (MCV 80-100 Fl)
⎯ Microcytic (MCV <80 fL)
⎯ Macrocytic (MCV >100 fL)

MICROCYTES
⎯ Size of RBC: 5 um or less
⎯ MCV < 80 fL
⎯ It happens in Hypochromic microcyte and Microspherocyte
⎯ Causes:
1. Increase erythropoiesis - In here, cytoplasmic maturation lags behind a nuclear
maturation. Lags means mabagal or retired yung development, if the development of
cytoplasm is slow what will happen? Usually in Hematophoiesis, as red blood cell
matures lumiliit yung Nucleus cytoplasmic maturation. Pero ang nagyayari natanggal
na yung nucleus sa ating blood cell. Si cytoplasm hindi niya pa tapos yung maturation
andun na siya sa stage ng mature red blood cell pero si cytoplasm hindi niya pa
nacocomplete yung maturation niya. As a result, nagkakaroon ng maliliit na rbc and
that is microcytes. Hindi sabay yung maturation ng cytoplasm and nuclear maturation
dahil sa INCREASE ERYTHROPOIESIS in which nagdedemand ng nag dedemand yung
body natin ng maraming red blood cell, since nag our body demands a lot of red blood
cells kahit hindi pa fully develop si cytoplasm irerelease na siya sa peripheral blood
circulation kaya nakakakita tayo ng microcytes.
2. Deprivation of Hb synthesis – in here, titignan natin yung mga conditions associated
with microcytic. What are the components of our hemoglobin? Our hemoglobin has
an iron, so if there is iron deficiency in a patient meron ba tayong mafoform na
hemoglobin? Definitely WALA kaya nagkakaroon tayo ng microcytic red blood cells
since inside the red blood cell we have hemoglobin, since we have no hemoglobin,
the red blood cell size will shorten kasi nga walang laman na hemoglobin. ANALOGY:
yung balloon, yung isang balloon hinipan mo ng air tas yung isa hindi, so yung hinipan
mo na balloon yung air na nasa loob niya yun ay HEMOGLOBIN then yung balloon is
red blood cell while yung other balloon na di mo hinipan na walang hangin tawag dun
ay microcytes.
A - ANEMIA OF CHRONIC DISEASE
T – THALASSEMIA
I – IDA
S - SIDEROBLASTIC ANEMIA
3. Defective globin synthesis – we have 2 types of hemoglobin or globin effects:
Hemoglobinopathies and Thalassemia.
HEMOGLOBINOPATHIES – it is a qualitative disorder of our hemoglobin or our globin
chains. In here there is substitution of globin chains and that is qualitative kaya
magiiba yung hemoglobin na mafoform. For example, HEMOGLOBIN Sc is not a usual
hemoglobin a normal hemoglobin, so if there is hemoglobin Sc there is a substitution
of amino acids or the globin chains. (Hemoglobin E, Hemoglobin C, Hemoglobin S
etc.)
THALASSEMIA – lack amount of globin chain or lack of amino acid that is being
formed kaya nagkakaroon ang isang tao ng thalassemia. There is no substitution.

⎯ Conditions: IDA, ANEMIA OF CHRONIC DISEASE, SIDEROBLASTIC ANEMIA,

THALASSEMIA
⎯ PROBLEM HERE IS CYTOPLASMIC MATURATION kaya maliit si red blood cell
MACROCYTES
⎯ Size of RBC: >9um
⎯ MCV >100 Fl
⎯ Conditions: pernicious anemia, folic acid deficiency, post splenectomy, after
chemotherapy, obstructive jaundice.
⎯ PROBLEM HERE IS NUCLEUS MATURATION
Variations of Macrocytes:
A. THIN MACROCYTES
⎯ MCV is normal and often hypochromic
⎯ Caused by increased membrane cholesterol and lecithin which is part of red blood
cell membrane so hindi dapat nag increase or decrease. So kapag nag decrease or
nag increase yan magkakaroon tayo ng variations.
B. OVAL MACROCYTES
⎯ Deficiency of vitamin B12 as folate
⎯ Don’t assume that if you have seen a vitamin B12 it is a macrocytic because we
need to detect whether the deficiency is vitamin B12 or folate
C. ROUND MACROCYTES
⎯ Seen in hepatic diseases, increase reticulocytosis, acute alcoholism and plasma aplastic
anemia causes decreased erythropoiesis, impaired DNA synthesis, young rbcs which
undergo early loss of nucleus.
⎯ Nuclear maturation lags behind cytoplasmic maturation. So, in here, NUCLEUS is
the problem. Lumalaki yung cytoplasm pero yung nucleus hindi pa siya fully
mature kaya ang lumalabas o ang narerelease sa peripheral blood smear ay
MALAKING CYTOPLASM since the problem here is the nucleus, not proportional
to the maturation of the cytoplasm. As a result, there is a MACROCYTES.
⎯ Ang nagdedevelop lang here is cytoplasm and not the nucleus kaya nakakakita
tayo ng malaking cytoplasm.

MACROCYTOSIS (HUBBARD)
1+ SLIGHT If there are approximately
25% macrocytic rbcs present
per high-power field.
2+ - 3+ MODERATE If there are 25% to 50%
macrocytic rbcs present per
high-power field.
4+ MARKED If there are >50% macrocytic
rbcs present per high-power
field.
NORMOCYTIC
⎯ Size of RBC: 6-9 um
⎯ MCV: 80-100 fL
⎯ Conditions: AHA
1. Acute hemorrhage – pagkakaroon ng sudden bleeding in which hindi siya associated sa
pagkakaroon ng red blood cell problem. Maaring may nasugatan sa katawan mo
napuncture ganun kaya ka ngakaroon ng bleeding. And these have nothing to do in red
blood cells.
2. Hemolytic anemia – walang red blood cell morphology abnormality dito. It depends on
the type ng pag cause ng hemolysis maaring external or antibodies or even drugs
3. Aplastic anemia – this is an anemia which causes decrease blood lineage formation.
mababa lahat ng blood cells at ang problema dito is yung bone marrow.
⎯ Kapag walang problema yung size ng red blood cell maaring iba yung cause ng kanilang
anemia. Kasi usually kapag may problem sa red blood cell may defective ng globin,
defective na hemoglobin, increase na erythropoiesis.

POIKILOCYTOSIS (VARIATION IN SHAPE)

Erythrocyte Nomenclature
Common Terms Synonyms
(Greek Terminology
Acanthocyte Acanthocyte
Blister cell
Burr cell Echinocyte
Crenated erythrocyte Echinocyte
Elliptocyte Elliptocyte
Helmet cell Schizocyte
Normal erythrocyte Discocyte
Oval macrocyte Megalocyte
Ovalocyte Elliptocyte
Pyknocyte
Schistocyte Schizocyte
Sickle cell Drepanocyte, meniscocyte
Spiculated erythrocyte
Spherocyte Spherocyte
Stomatocyte Stomatocyte
Target cell Codocyte
Teardrop Dacryocyte
Keratocyte
Knizocyte
Leptocyte
FIGURE 6.5
Variations in erythrocyte shape.
A: normal RBCs (RBCs) (discocytes);
B: acanthocytes;
C: blister cells;
D: burr cells;
E: poikilocytes;
F: crenated RBCs (echinocytes);
G: elliptocytes;
H: helmet cells (schizocytes);
I: leptocytes;
J: oval macrocytes (megalocytes);
K: schistocytes (schizocytes);
L: sickle cells (drepanocytes);
M: spherocytes;
N: stomatocytes;
O: target cells (codocytes);
P: teardrops (dacryocytes)

⎯ Poikilocytes are damaged and/or rigid red cells. The function of the spleen - Pitting and
the culling. Other red blood cells with abnormality on their shape or morphology they are
being damage or hemolyze by the macrophages in the spleen. How come that there are
poikilocytes present in the peripheral blood smear? E sinisira na nga sila ng
macrophages sa spleen palang, take note that this occurs in certain diseases and the
spleen cannot breakdown all of these blood cells kaya maraming poikilocytes imagine sa
spleen, si spleen is maraming function at hindi lang naman si red blood cell ang
brinebreakdown niya kundi pati ibang mga blood cells that is why it is difficult for the
spleen to accommodate all cells kaya pati yung ibang poikilocytes is nakakapasok na to
that filter area kaya nakakita tayo ng poikilocytes sa smear.
⎯ ACANTHOCYTES – other term is spur cell or thorn cell. Have multiple thorny, spike-like
projections that are irregularly distributed around the cellular membrane and may vary in size.
Why does the red blood cell have a spike on its periphery? Remember the content of our red
blood cell we have sphingomyelin and lecithin but the most abundant in blood cells particularly
in red blood cells is lecithin but in the acanthocytes the most abundant is sphingomyelin so there
is an imbalance therefore, imbalance yung lipid content ng acanthocytes. So what happens here,
supposedly yung sphingomyelin dapat mapupunta siya sa ating plasma but it can not be
reabsorbed in the small intestine, yung lipids supposedly ay na-absorbed sa small intestine
going to plasma but then hindi siya nagyayari there is a capacity to absorb excess lipids and
napupunta sila sa red blood cells kaya nagiging thorny or spike-like projections or around ng
ating membrane or ng red cell mebrane.
⎯ RBCs with irregularly spaced projections. Projections vary in width but usually contain a rounded
end.
⎯ Acanthocytes are prevalent in two very different disorders:
1. Abetalipoproteinemia - a rare hereditary disorder, and spur cell anemia that there is a
influx of lipids in this disease.
2. Liver disease – lipids cannot be metabolized kasi nga may problema si liver kaya may
influx sa lipids
3. Mcleod blood group phenotype – which has an acanthocytes.
4. Post- splenectomy – katatanggal nung spleen kaya walang magfifilter sa ating red blood
cells kaya nakakakita tayo ng acanthocytes.

SPHEROCYTES
 ⎯ RBCs lacks the biconcave shape and becomes more spherical; no central pallor is present
with increased hemoglobin content. They are found in heredity spherocytosis (increase
amount of spherocytes), hemolytic anemia (all hemolytic anemia is associated with
spherocytes) and post transfusion
⎯ Walang nakikitang halo sa gitna
⎯ KULANG NA PROTEIN HERE IS SPECTRIN.
⎯ Decrease surface to volume ratio kaya wala tayong nakikitang central pallor
⎯ Nagkakaroon tayo ng spherocytes, the defect of the spherocyte is in the spectrin, wala
siyang spectrin kaya nagiging sphere or spherical yung ating red blood cell kaya mabilis
siyang mag breakdown mabilis siyang ma-lyse. There are some instance na makikita
natin sila sa blood smear particularly in post transfusion. Aside from this, if there is no
problem in the spleen baka may problema mismo sa erythropoiesis itself.
⎯ Red blood cell should have spectrin to become deformable and not easily to be lyse.
⎯ Bronze cell

OVALOCYTES
⎯ Oval shaped RBCs (red blood cell shape must not be sphere, oval, not as elongated but
it is DISK in shape)
⎯ Ovalocytes are found in:
1. Thalassemia major
2. Heredity ovalocytosis
3. Sickle cell anemia
⎯ Elongated, oval cells which tend to become more elongated as the cell ages
⎯ Elongation may be due to redistribution of hemoglobin or cholesterol to ends.
⎯ We acquire ovalocytes because the cholesterol content of the red blood cell is being reduce or
decrease. This cholesterol is found in the cell membrane of the red blood cell. So, if there is
decrease in the cholesterol content our red blood cell will easily change in its shape, a oval
shape.

ELLIPTOCYTES
⎯ Cigar shape or sausage shape RBC, this shape is due to the defect of the cytoskeleton
particularly the membrane protein band 4.1.
⎯ Problem here: variation in shape, which is nagiging cigar shape yung red blood cell.
There is a problem in the cytoskeleton particularly the membrane protein band 4.1.
⎯ the RBCs are oval or elliptical in shape, long axis is twice the short axis.
⎯ Are found in:
1. Heredity elliptocytosis
2. Megaloblastic anemia
3. IDA
4. Thalassemia
5. Myelofibrosis

TARGET CELLS
 ⎯ Red cell have an area of increase staining which appears in the area of central pallor
⎯ Target cells are found in:
1. Obstructive liver disease
2. Severe IDA (iron deficiency anemia)
3. Thalassemia
4. Hemoglobinopathies
5. Post splenectomy
⎯ Target cells (codocytes)
⎯ Mexican hat cell because it looks like a hat of the Mexican
⎯ It can also be found as an artifact (ibig sabihin dahil lang sap ag smear mo dahil sa
pressure ng pag smear natin nakaform tayo ng target cells
How does it happen?

⎯ Hemoglobin here is concentrated kaya may nakikita tayong dot sa gitna ng red blood cell
and this happen in increase surface to volume ratio.
⎯ in target cells, excessive cholesterol in the membrane or an imbalance between the
hemoglobin kasi concentrated siya sa gitna

TEARDROP CELLS
⎯ RBCs having the shape like teardrop or pear. These are usually microcytic and often
hypochromic
⎯ Teardrop cells are found in:
1. Myelofibrosis – very common here or the INFILTARTION OF THE BONE MARROW.
2. Megaloblastic anemia’
3. IDA
4. Thalassemia
⎯ Dacryocytes, racquet forms
⎯ If there is teardrop cells there is also myelofibrosis

SCHISTOCYTES
⎯ These are helmet or triangular shaped, fragmented or greatly distorted RBCs smaller than
normal size.
⎯ We have schistocytes dahil nagkakaroon tayo ng fragmentation ng taing red blood cells.
⎯ Schistocytes are seen in
1. Thalassemia – schistocytes usually seen in this condition
2. Microangiopathic hemolytic
3. Anemia
4. Mechanical hemolytic anemia
5. Uremia’
6. Artificial heart valves.
⎯ Schistocyte/ schizocyte/ keratocyte/helmet/bite cell
STOMATOCYTES
⎯ Red cells with a central linear slit or stoma. Seen as mouth shaped form in peripheral smear
⎯ Are found in:
1. Excess alcoholism
2. Alcoholic liver disease
3. Hereditary stomatocytosis
⎯ Mouth or kiss cells
⎯ Pavertical shape para siyang may slit. Stomatocytes have a slit in shape due to the
imbalance on the osmotic pressure or an osmotic change on the middle of the red cell
because there is an imbalance of sodium and potassium. It might be the level of sodium
is higher or the potassium is higher. VISE VERSA. Imbalance sa mga cation.

KERATOCYTES
⎯ These are half-moon shaped cells with two or more spicules.
⎯ Pag may OXIDATION nagiging keratocytes shape si red blood cell
⎯ Commonly seen in:
1. G6PD Deficiency – prone to oxidation and as result there is a keratocytes (product
of oxidation) aside from Heinz bodies.
2. Pulmonary embolism
3. Disseminated intravascular coagulation

BURR CELLS
⎯ Red cells with uniformly spaced pointed projections on their surface.
⎯ Also known as sea urchin or cremated red blood cell
⎯ We have OSMOTIC IMBALANCE here. Projection on the gilid of our red blood cell
membrane
⎯ The difference between burr cells and acanthocytes is that, in burr cells evenly distributed the
projections of the red blood cell in its periphery while in acanthocytes it has a different projection
in its periphery or gilid ng red blood cell membrane.
⎯ BURR CELLS – uniformly spaced
⎯ Acanthocytes – not uniformly spaced
⎯ Are found in:
1. Hemolytic anemia
2. Uremia
3. Megaloblastic anemia

SICKLE CELLS
⎯ These are sickle-shaped red blood cells
 ⎯ Sickle cells are seen in Hb-S disease/ sickle cell anemia
1. Hemoglobin SS disease
2. Hemoglobin SC disease
3. Hemoglobin SD disease
4. S-beta thalassemia

Keratocytes
⎯ are erythrocytes that are partially deformed but not cut. The spicules, resembling two horns,
result from a ruptured vacuole. Usually, the cell appears like a half-moon or spindle. These cells
are seen in conditions such as disseminated (diffuse) intravascular coagulation (DIC).

Blister cells
⎯ are erythrocytes containing one or more vacuoles that resemble a blister on the skin. This cell
has a significantly thinned area at the periphery or outer border of the cell membrane. The
vacuoles may rupture. If rupturing does occur, distorted cells (keratocytes) and cell fragments
(schistocytes) are produced.

Knizocytes or pinch cell

⎯ resemble a pinched bottle. This abnormality is associated with hemolytic anemias, including
hereditary spherocytosis.
⎯ Triangular with 2 pallor edges resembles a pinched bottle. This abnormality Is associated with
hemolytic anemias, including heredity spherocytosis.

Description of red blood cell RBC abnormalities and commonly associated disease states

RBC ABNORMALITY CELL DESCRIPTION COMMONLY ASSOCIATED

DISEASES STATES
Anisocytosis Abnormal variation in RBC Hemolytic, megaloblastic,
volume or diameter iron deficiency anemia
macrocyte Large RBC (>8 um in Megaloblastic anemia
diameter), MCV >100 fL Myelodysplastic syndrome
Chronic liver disease
Bone marrow failure
reticulocytosis
Oval macrocyte Large oval RBC Megaloblastic anemia
Microcyte Small RBC (<6 um in Iron deficiency anemia
diameter), MCV <80 fL. Anemia of chronic
inflammation
Sideroblastic anemia
Thalassemia/Hb E disease
and trait.
Poikilocytosis Abnormal variation in RBC Severe anemia; certain
shape shapes helpful diagnostically
Hb Crystal Hexagonal crystal of dense Hb C disease
hemoglobin formed within the
RBC membrane
Hb SC crystal (Washington Fingerlike or quartz-like Hb SC disease
monument) crystal of dense hemoglobin
protruding from the RBC
membrane
Target cell (condocyte) RBC with hemoglobin Liver disease
concentrated in the center Hemoglobinopathies
and around the periphery Thalassemia
resembling a target
Schistocyte (schizocyte) Fragmented RBC due to Microangiopathic hemolytic
rupture in the peripheral anemia” (along with
circulation microspherocytes).
Macroangiopathic hemolytic
anemia**
Extensive burns (along with
microspherocytes).
Helmet cell (keratocyte) RBC fragment in shape of a Same as schistocyte
helmet
Folded cell RBC with membrane folded Hb C disease
over Hb SC disease
Acanthocyte (spur cell) Small, dense RBC with few Severe liver disease (spur cell
irregularly spaced anemia)
projections of varying length Neuroacanthocytosis
(abetalipoproteinemia,
Mcleod syndrome)
ANISOCHROMIA (Variation in hemoglobin content)
⎯ Red blood cells differ in color depending on the amount or the concentration of
hemoglobin
⎯ The color of the red blood cell depends on the hemoglobin content
⎯ Variation in the hemoglovin content
1. Hypochromic cell – associated with miroscytic red blood cells
2. Hyperchromic cell – it is not seen in some diseases. It is associated with
spherocytes called agglutinins or error in intestine
3. Normorchromic cell – associated with macrocytic and normocytic
Normochromic (MCHC = 31-36%) beyond 36% that is HYPERCHROMIC. And if it is greater than
36% MCHC usually it is not associated with dsease but in cold agglutinins, sample that has been
refrigerated and not taken back on his room temperature and aother one is spherocytes and
dito din nagfafall yung ating mga macrocytic.
Hyperchromic (MCHC = 36%)
Normochromic and hyporchromic are the most common anisochromia in the laboratory

⎯ We can just tell whether the cell is Hypochromic, hyperchromic or normochromic when we
compute the value of our MCHC

NORMOCHROMIC
⎯ A normal erythrocyte has a moderately pinkish-red appearance with a lighter-colored center
when stained with a conventional blood stain.
⎯ The color reflects the amount of hemoglobin present in the cell.
⎯ The lighter color in the middle, thinner portion of the cell does not normally exceed one third of
the cell’s diameter and is referred to as the central pallor.
⎯ A NORMAL ERYTHROCYTE CONTAINS AN AMOUNT OF HEMOGLOBIN SO ONLY 1/3 OF
ITS DIAMETER IS EMPTY IN APPEARANCE (NORMOCHOMIC)
HYPOCHROMIA
⎯ Indicates the amount of hemoglobin in the erythrocyte decreased and the central pallor
area is greater than 1/3 the re cell diameter; THE MCHC MAY BE <32.0%.
⎯ Decreased in hemoglobin content = increased central area of pallor which is greater than
1/3 of the red cell diameter.
⎯ The hemoglobin content and the central area of pallor is inversely proportional. Ibig
sabihin kapag matass si hemoglobin content maliit lang yung central area of pallor, kapag
mababa si hemoglobin content Malaki si central area of pallor.
⎯ is more commonly used when the central pallor exceeds one third of the cell’s diameter or the
cell has a pale overall appearance.

HYPOCHROMIA GRADING
1+ ½. Area of central pallor is one half of cell
diameter
2+ 2/3. Area of pallor is two-thirds of cell
diameter
3+ ¾. Area of pallor is three-quarters of cell
diameter
4+ Thin rim of hemoglobin

HYPERCHROMIC/ HYPERCHROMIA/ HYPERCHROMASIA

⎯ these are seen in RBC with seemingly increased in Hb content since the cell is thicker than
normal but the hemoglobin content is actually within the normal limit
⎯ IT SEEMS THAT THE HEMOGLOBIN IS IN HIGH AMOUNT BUT IN REALITY, NASA
NORMAL UNIT NAMAN. KASI MAY IMBALANCE THE HEMOGLOBIN CONTENT.
POLYCHTOMASIA/POLYCHROMATOPHILIA
⎯ Large red cells (8-10u) which display diffuse basophilia (blue tinge) due to residual RNA when
stained with Wright’s stain. The amount of polychromasia correlates with the number of
circulating reticulocytes.
⎯ We talk about residual RNA component of the red blood cells, usually dapat wala na si
RNA when there is a mature red blood cells. kapag may RNA pa yung red blood cell that
means that our red blood cell under the peripheral blood smear ay galling sa early
precursor like polychromatophilic normoblast
⎯ RETICULOCYTES have a residual RNA, aside from polychromatophilic normoblast yung
ating reticulocytes or yung ating polychromatophilic erythrocytes is may residual RNA
din

POLYCHROMASIA GRADING
GRADING POLYCHROMATOPHILIC RBCs
slight 1%
1+ 3%
2+ 5%
3+ 10%
4+ >11%

INCLUSION BODIES
Inclusions in the erythrocyte
⎯ Normal RBC – no inclusions
⎯ The presence of inclusions decreases red cell deformability and shortens red cell survival
⎯ Red blood cell that has inclusions is nakakalagpas sila sa spleen, even they pass on the
spleen, later on maphapagocytosize and they are not deformable and the reason na hindi
sila makakapasok sa maliliit na passage way sa tissues.

HOWELL-JOLLY BODIES
⎯ Small round cytoplasmic red cell inclusion with same staining characteristics as nuclei. These
are FRAGMENTS OF DNA.
⎯ Usually seen in:
1. post splenectomy – walang spleen, so wala ring magfifilter dito sa inclusion.
(Pitting and culling)
2. megaloblastic anemia – hypersegmented, hypersegmented ovalocytes, and
Howell-jolly bodies (triple H) these are seen in megaloblastic anemia
3. hemolytic anemia – we also see Howell-jolly bodies here
HEINZ BODIES
⎯ these represent denatured hemoglobin (methemoglobin) within a cell. With a supravital
stain like crystal violet, Heinz bodies appear as round blue precipitates or may be a product
of abnormal globin synthesis and composed of unused, precipitated globin chains.
⎯ Seen in:
1. G6PD deficiency
2. Splenectomy
3. Oxidant drugs – kasi nagproproduce siya ng oxidation and lead to the precipitation
of Heinz bodies
4. Favism and unstable hemoglobin – hemoglobin should be stable. Why? Because
once our hemoglobin is unstable it will be prone to oxidation.
PAPPENHEIMER BODIES
⎯ These represent iron deposits which as dense blue, irregular granules in wright’s stain
⎯ Distributed in periphery only of red blood cell
⎯ Pappenheimer bodies are found in RBCs with:
1. Hemolytic anemia – when red blood cell is hemolyze, there is iron component in
the heme so the iron will deposited in red blood cells that is why we have iron
deposits in the red blood cells
2. Splenectomy – hindi matatanggal si inclusion.
3. Sideroblastic anemia – kaya natin to nakikita dahil sa iron deposits. Iron can be
deposited as siderophile granules or sideroblasts
4. Thalassemia – quantitative defect if globin synthesis. When we lack of globin sobra
naman tayo sa iron or sa ating heme. If there is excessive heme it will result to
imbalances with globin kaya nadedeposit nalang si iron ng basta basta sa mga red
blood cells.
⎯ Iron deposits sa gilid (pereiphery) ng red blood cell

BASOPHILIC STIPPLING
⎯ These are considerable amount of small basophilic inclusions in red cells which represent
precipitated RNA.
⎯ Distributed on the entire red blood cells
⎯ Seen in the:
1. Thalassemia
2. MBA
3. Hemolytic anemia
4. Liver damage
5. Heavy metal poisoning
6. Lead poisoning
CABOT RING
⎯ Reddish, purple, thread-like rings in RBCs of severe anemias; FIGURE OF EIGHT RBC using
Wright’s stain.
⎯ These are the remnants of mitotic spindle, microtubules
⎯ Seen in patient with:
1. Megaloblastic anemia
2. Myelodysplastic syndrome
3. Lead poisoning.
SUMMARY:
STAINING CHARACTERISTICS OF ERYTHROCYTES AND INCLUSIONS
STAIN
INCLUSION Feulgen Supravital Wright
Basophilic stippling Negative Positive Positive
Cabot rings Negative Negative Positive
Howell-Jolly bodies Positive Positive Positive
Polychromatophilia Negative Negative Positive
Reticulocytes Negative Positive Negative
Pappenheimer bodies Negative Positive Positive
Heinz bodies Negative Positive Negative
Feulgen stain demonstrates the presence of DNA.
Supravital stains (e.g., new methylene blue or brilliant cresyl blue) demonstrate the presence of
RNA.
Can be demonstrated with crystal violet stain.

MALARIAL INCLUSIONS
⎯ The inclusions may be ringed, segmented or massive forms depending on the maturity of
the parasite
⎯ Associated with infestation of:
1. Plasmodium vivax (schuffner’s granules) – VILMA SANTOS
2. Plasmodium falciparum (Mauer’s dots) – FERDINAND MARCOS kapag may
nabanggit na other dots sagot is Faciparum.
3. Plasmodium malariae (Zeiman’s dot) – MANILA ZOO
4. Plasmodium ovale (James dots) -ORANGE JUICE
OTHER PROTOZOAN INCLUSIONS
1. Babesia microti – ringlike structures resembling malarial parasite; Maltese cross.
Confused with the ring of the Plasmodium falciparum
2. Bartonella – comma-shaped organism near membrane. Usually categorized this
as bacteria.
HEMOGLOBIN C CRYSTALS HEMOGLOBIN SC CRYSTALS

CHARACTERISTICS: Condensed rod or bar- CHARACTERISTICS: Bizarre shaped crystal;

shaped crystals with blunt ends found in RBCs. denser than sickle cells with fingerlike
Tetragonal, rectangular rod shaped (bar of gold, projections. “Washington Monument” shape
clam shell)
Associated with: Associated with:
Inherited presence of hemoglobin C. Inherited presence of Hgb S and Hgb C (Hgb
SC).
SUMMARY OF INCLUSIONS:
INCLUSION APPEARANCE APPEARANCE INCLUDION ASSOCIATED
IN IN WRIGHT’S COMPOSED DISEASES/CONDITIONS
SUPRAVITAL STAIN OF
STAIN
Diffuse Dark blue Bluish tinge RNA Hemolytic anemia
basophilia granules and throughout After treatment for iron
filaments in cytoplasm; Vitamin b12, or folate
cytoplasm also called deficiency
(seen in polychromasia
reticulocytes) (seen in
polychromatic
erythrocytes)
Basophilic Dark blue- Dark blue- Precipitated Lead poisoning
stippling purple, fine or purple, fine or RNA Thalassemia
coarse coarse Hemoglobinopathies
punctate punctate Megaloblastic anemia
granules granules Myelodysplatic
distributed distributed syndrome
throughout throughout
cytoplasm. cytoplasm.
Howell-jolly Dark blue- Dark blue- DNA (Nuclear Hyposplenism
body purple dense, purple dense, fragmented) Postsplenectomy
round granule; round granule; Megaloblastic anemia
usually one per usually one per Hemolytic anemia
cell; cell; Thalassemia
occasionally occasionally Myelpdysplastic
multiple multiple syndrome
Heinz body Round, dark Not visible Denatured G6PD deficiency
blue-purple hemoglobin Unstable hemoglobins
granule Oxidant
attached to drugs/chemicals
 inner RBC
membrane
Pappenheimer Irregular Irregular Iron Sideroblastic anemia
bodies clusters of clusters of Hemoglobinopathies
small, light to small, light to Thalassemia
dark blue dark blue Megaloblastic anemia
granules, often granules, often Myelodysplastic
near periphery near periphery syndrome
of cell of cell Hyposplenism
Post-splenectomy
Cabot ring Rings or figure- Blue rings of Remnant of Megaloblastic anemia
eights figure-eights mitotic Myelodysplastic
spindle syndrome
Hb H Fine, evenly Not visible Precipitate of Hb H disease
dispersed, dark beta-globin
blue granules; chains of
imparts “golf hemoglobin
ball”
appearance to
RBCs
 MICROCYTIC AND HYPOCHROMIC ANEMIA
Red Blood Cell Disorders
Microcytic-Hypochromic Anemia
Anemia of chronic inflammation, Thalassemia, Iron deficiency anemia, Sideroblastic
anemia.
Microcytic – The MCV is less than 80
Hypochromic – The MCHC is less than 31

-Due to defective hemoglobin synthesis resulting to cytoplasmic maturation defect

- In microcytic anemia or microcytes the problem is cytoplasmic maturation. Kaya nga
maliit and ating cell. And particularly yung hemoglobin synthesis.

What are the factors that could contribute in a defective hemoglobin synthesis?
1. DEFECTIVE HEME SYNTHESIS
• Abnormalities of iron homeostasis (deficiency of metabolism)
• Meaning, sometimes kapag defective ng metabolism. We have 2 types of
metabolism. It can be formation or breakdown
• Formation – may mabubuong complex
• Breakdown – We will be dividing or breaking down the molecule or the complex
substance into its simpler form.
• Ang nangyayari dito sa ating iron homeostasis kulang yung metabolism. That’s
why it might be excess iron or deficiency in iron. Iron is in the heme portion.
Kapag kulang tayo ng iron hindi tayo makaka buo ng heme. Kapag sobra ng iron
magiging abnormal or defective yung ating heme.
• Take note there is a balance number of iron that would be present in one
molecule of heme
-SIDEROPENIC ANEMIA – commonly known as the iron deficiency anemia IDA
→ It is usually associated with iron. Penic or penia decrease
-SIDEROACHRESTIC ANEMIA – adequate or excess iron but defective
utilization
→ Sidero is for iron. Achrestic is just a projection or an increase amount.
→The hemoglobin cannot function well
o Anemia of Chronic Inflammation
o Note that inflammation triggers our body to produce substances. If you
could remember in Immunology. The acute phase reactants and the
negative acute phase reactants.
• Defective porphyrin metabolism
-SIDEROBLASTIC ANEMIA
- Blasts - Immature form of porphyrin
2. DEFECTIVE GLOBIN SYSNTHESIS
- When we say globin synthesis, that is a portion of hemoglobin
- Thalassemia is a quantitative defect of globin. May kulang siya sa Alpha globin or beta
globin. Kaya nagkakaroon tayo ng different types of Thalassemia
- Take note when we say globin these are the amino acids or chains that is present in
our hemoglobin.
• Results to Thalassemia
• Deletion or maturation of globin genes

List of Microcytic/Hypochromic anemia

1. IRON DEFICIENCY ANEMIA
• Most common form of anemia
• Prevalent in infants and children – infants and children don’t have enough
amount of iron. Because iron can be produced in the body but they also need to
have intake of iron or they need to have supplement for iron.
• Pregnancy – the growing fetus inside the womb of the mother also needs iron,
the baby needs the iron of the mother that’s why mababa and iron sa circulation
ni mother kasi nakiki share si baby sa iron ni mother.
• Excessive menstrual flow – if you could imagine continuous blood loss and
there is iron in our blood.
• Elderly with poor diets – Geriatric patients or elder patient cannot absorb iron
from food and kulang na din ang iron stores in their body kaya it is recommended
to our elderly patients to take supplements
• Malabsorption syndromes – It is mechanism in the body to absorb nutrients
from our food, so dapat na aabsorb ng ating intestine yung iron sa ating pagkain
• Chronic blood loss – similar to excessive menstrual flow

• ETIOLOGY
a. Inadequate intake of iron
→ If you don’t eat enough food that is rich in iron, you will have an inadequacy of
iron lalo na kung kulang yung iron stores mo as katawan.
b. Increase demand
→The normal response of the body once there is a decrease or decline iron
stores, mag dedemand yan sa katawan ng increase iron.
c. Impaired iron absorption
→ This is similar to malabsorption
d. Chronic blood loss
Clinical signs and symptoms
• Fatigue, weakness, and shortness of breath, especially with exertion, sore
tongue (glossitis), inflamed cracks at the corners of the mouth (angular cheilosis),
 Koilonychia (spooning of the fingernails) may be seen if the deficiency is long-
standing. Patients also may experience cravings for nonfood items, called pica.
• PICA = The cravings may be for things such as dirt, clay, laundry starch.

STAGES OF IDA (IRON DEFICIENCY ANEMIA)

STAGE DESCRIPTION HEMOGLOBIN SERUM TIBC FERRITIN

IRON (Total iron
binding
capacity)
Stage 1 Storage Normal Normal Normal Decreased
depletion
-Storage form -Usually, -Normal pa -It is normal -Affected
of iron is the normal kasi yung kasi ang storage
ferritin. hemoglobin storage iron problema form of
Sometimes kasi meron pa natin lang naman iron. So,
when there is naman other sometimes ay ang decrease
an increase forms of iron it is found in storage
iron in our na nasa blood, our liver form, baka
body, ma excess lang tissues naman may
iistore yung iba naman itong enough iron
para later on storage iron so pa sa ating
kapag meron pa circulation
kailangan ng tayong
iron ng magagmit for
katawan or hemoglobin
kailangan ng synthesis kaya
iron for the usually normal.
development
of heme and
hemoglobin
may
mahuhugot
yung ating
katawan.
Stage 2 Transport Normal Decreased Increased Decreased
depletion
-Kulang yung -Since may -Serum iron - TIBC
stored iron + mga is measure the
kulang yung magagamit pa decreased available
transport naman tayo in kasi yung space where
protein. It the blood. transferrin iron binds.
means walang Usually ang is usually Since,
mag mga found in the kulang ng
tatransport na tinatransport serum or in iron. Yung
iron, kaya hindi lang ay yung the plasma. TIBC ay
 available si mga na sstore Since wala maraming
iron sa ating na iron so it is tayong I binding site
circulation or usually normal tatransport e walang
sa ating blood na iron wala iron so
tayong walang mag
madedetect babind sa
na binding site
transferrin kaya
nagkakaroon
ng increase
TIBC
Stage 3 Functional Decreased Decreased Increased Decreased
depletion
-This stage is -Hindi na kaya -Decrease -Same with
critical. makapag form din kasi stage 2
Storage iron, ng hemoglobin lahat
transport iron dahil kulang na effected
since there is at hindi na
no stored iron kaya makapag
hindi mo pa ma form ng
transport yung hemoglobin.
iron kasi wala Naubos na ang
ka ngang iron sa ating
stored iron, circulation and
and pano mag wala pa tayong
fafunction yung storage iron
hemoglobin kaya nag
kung walang dedecrease
iron. That yung ting
would lead to hemoglobin
functional count.
depletion.

Parasites associates with IDA (iron deficiency anemia)

• Hookworms
• Trichuris trichiura
• Schistosoma mansoni
• Schistosoma haematobium