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Poikilocytosis:
Abnormalities of Erythrocyte Shape
Jennifer Weisent, DVM;
Bruce E. LeRoy, DVM, PhD; Perry J. Bain, DVM, PhD; Kenneth S. Latimer,
DVM,
PhD
Class of 2003, Ross University,
School of Veterinary Medicine, St. Kitts, West Indies (Weisent) and Department
of Pathology (LeRoy, Bain, Latimer), College of Veterinary Medicine, The University
of Georgia, Athens, GA 30602-7388
Introduction
Poikilocytosis is a general
term referring to erythrocytes of abnormal shape.2,3 This rather non-specific
term is used to describe an unusually high (greater than 10%) population of
abnormally shaped RBC’s in peripheral blood.2,3 These erythrocyte morphological abnormalities may be caused by a variety
of conditions, including fragmentation of erythrocytes, oxidative injury,
immune-mediated damage, and congenital abnormalities.2 The presence
of poikilocytes is considered to be normal in young
ruminants, especially goats.3 Poikilocytes usually are not considered highly sensitive or specific indicators of disease;
however, familiarity with common erythrocytic morphological changes may help
veterinarians identify the underlying causes of disease in some animals.
Fragmentation of erythrocytes
refers to cells that have been mechanically damaged in circulation. Damage
may be the result of turbulent blood flow or deposition of fibrin strands.
Fragmentation of erythrocytes may occur in infection, inflammation, and neoplasia
when sufficient damage to endothelial surfaces results in fibrin deposition.1 Oxidative injury, on the other hand, is usually associated with exposure
to endogenous or exogenous circulating toxins, which may cause subsequent
denaturation of hemoglobin and/or membrane lipid peroxidation.1,2 Immune-mediated damage of erythrocytes often is characterized by the presence
of spherocytes and extravascular hemolysis.2,3 However, intravascular hemolysis
also may occur.3
Several in vitro conditions can result in artifactual poikilocytosis, that should be distinguished,
if possible, from poikilocytosis in vivo resulting from disease.
Crenation, a form of
echinocytosis, can result from drying a smear too slowly, excess anticoagulant,
prolonged blood storage, and surface temperature differences between cell
and slide.2 Secondly, round to crescent-shaped, vacuole-like,
clear areas (drying artifact) are likely to
occur in erythrocytes when there is insufficient drying time before staining.2 In preparations that are too thick, erythrocytes may be distorted and mimic stomatocytes.
Keratocyte formation
can be seen in feline erythrocytes from EDTA-anticoagulated blood specimens
following prolonged storage.3
Dacrocytes (tear drop
cells) also may occur from improper slide preparation (i.e.,smearing
of RBCs with excessive pressure).5 Fortunately, this artifact
is easily distinguished from true dacrocytosis, as the tear drop-shaped
cells will have a unidirectional, rather than random, orientation on the
slide.
Slow drying of blood
smears in a humid environment or from blood samples with excessive anticoagulant
can result in the artifactual appearance of codocytes (target cells).5 Codocytes formed in vitro will be visible in high number in some
microscopic fields of view, but few of these cells will be observed in other
fields. In contrast, codocytes formed in vivo will be scattered
randomly throughout the blood smear.2
The following table contains
the physical appearance and pathogenesis of various types of poikilocytes.
Additional information concerning specific types of poikilocytes can be found
in the highlighted links. This table contains the diseases and disorders associated
with poikilocytosis in both humans and animals.
Table
1. Description of poikilocytes, mechanism of formation,
and related diseases and disorders
| Clinical
Significance in: |
| Type
of Cell |
Description |
Pathogenesis |
Dog/Cat |
Equine/other |
Human |
Schistocyte
Schizocyte |
Triangular
or helmet shaped fragments of RBC with sharp, pointed projections, and irregular
borders |
Fragmentation from impact
with fibrin strands, walls of diseased vessels, artificial surfaces, and
turbulent blood flow |
Microangiopathic
hemolytic anemia, DIC, iron deficiency, myelofibrosis, liver disease, heartworm
disease |
Not
typically seen in DIC (cat/horse) |
Microangiopathic
and uremic hemolytic anemia, DIC, pulmonary emboli, endocarditis |
Keratocyte
(Horn cells) |
Contains
one or more intact or ruptured vesicles (non staining)
May appear spindle shaped |
Rupture
or removal of circular area of apposed, sealed cellular membrane (viewed
as vesicle)
One or two projections formed |
Iron
deficiency anemia, liver disease, doxorubicin toxicity, myelodysplastic
syndrome. |
Endothelial
damage, Fibrin depo (in highly vascular organs) |
DIC,
Vascular prosthesis, Thrombotic thrombocytopenia purpura (TPP) |
| Blister
cell |
Contains
one or two eccentric, sharply defined, vacuole-like structures
May be precursor to keratocytes |
Hemodynamic
forces adhere RBC’s to obstacles (fibrin, thrombi); dislodgement results
in described membrane abnormalities |
Seen
in diseases associated with keratocytes |
|
Disease
of traumatic interaction between blood vessels and blood |
| Heinz
bodies |
Single,
smooth, rounded inclusions or protrusions
often with a pale ring of cytoplasm around the projection |
Precipitation
of denatured hemoglobin (usually due to oxidative injury) |
Suggestive
of hemolytic crisis; oxidant drugs or diet, zinc toxicosis |
Oxidants
in diet
Cat: oxidant
drugs, DM, lymphoma, hyperthyroidism, chronic renal disease
Horse: phenothiaz-ine deworm |
Seen
with unstable hemoglobinand defective RBC glycolytic enzymes |
Eccentrocytes
(Hemighosts) |
Eccentric
"ghosted" region of cytoplasm; remaining cytoplasm is condensed
slightly |
Hemoglobin
localized to half of cell; hemoglobin-poor area appears pale (membrane
"ghost")
Usually caused by oxidative injury to cell membrane |
Exogenous
toxins:
acetaminophen, propyl disulfide
(onions), naphthalene, zinc, vitamin K, analgesics |
Horse:
red maple leaf. G6PD deficiency, glutathione reductase def/FAD def. |
|
| Pyknocyte |
Eccentrocytes
that have become spherical; only small tag of cytoplasm remains |
Result
of membrane distortion and contraction |
See
eccentrocytes (above) |
|
Normal
in first few months of life |
Acanthocytes
(Spur
cell) |
Contain
irregularly distributed spicules of varying length and diameter |
RBC
membranes contain excess cholesterol compared to phospholipids
Alterations of plasma lipid composition subsequently alters RBC lipid
composition |
Liver
disease, hemangiosarcoma, DIC, glomerulonephritis |
|
Abetalipoproteinemia
liver disease, post spenectomy |
Echinocytes
(Crenated/Burr cells) |
Many
uniform, blunt or sharp pointed projections evenly distributed on cell membrane |
Outer
lipid monolayer of cell membrane has higher surface area than inner monolayer
(i.e., alteration of intra- or extracellular environment, pH changes,
dehydration of RBC, depletion of ATP, fatty acid accumulation on RBC surface) |
Envenomation
(snake), uremia, glomerulonephritis, neoplasia |
Depletion
of cations from endurance exercise, furosemide treatment, or systemic disease |
Pyruvate
kinase deficiency, neonates, uremia, effect of salicylates and barbiturates,
peptic ulcers |
Elliptocytes
(Ovalocytes) |
Cigar-
or egg-shaped RBCs with smooth or scalloped borders.
Usually flat instead of biconcave |
Often
hereditary
Can
be acquired
Normal in
nonmammals and Camelidae family |
Dog:
hereditary, myelofibrosis, myelodyplastic syndrome, glomerulonephritis, |
Cat:
bone marrow abnormalities, hepatic lipidosis, portosystemic shunts, doxorubicin
toxicity |
Hereditary,
various anemias (megaloblastic) |
Codocytes
(Target cells) |
Bell
shaped cells with central density or "bull’s eye" appearance |
Central
condensation of hemoglobin surrounding a clear zone, accumulation of membrane
phospholipids and cholesterol, congenital |
Regenerative
anemia, congenital dyserythropoeisis, normal in canine blood in small numbers |
|
Liver
disorders, iron deficiency, thalassemia, hemoglobinopathies, post splenectomy |
| Leptocytes |
Thin
cells with increased membrane to volume ratio, often hypochromic in appearance,
may appear folded or as triconcave knizocytes |
Balanced
accumulation of membrane phospholipids and cholesterol (as with codocytes) |
Iron
deficiency anemia, hepatic insufficiency (rare) |
|
|
| Stomatocytes |
Cup-shaped
with oval or elongated areas of central pallor, uniconcave |
often
artifactual, occur when RBC water content increases, alteration of cation
content and flux |
Hereditary
amphipathic drug use |
|
Hereditary,
liver diseases, alcoholism |
| Spherocytes |
Small,
spherical cells lacking
central |
Result
from partial removal of RBC membrane by monocyte-macrophage system
Decreased membrane surface area:cytoplasmic volume ratio |
Immune-mediated
damage (IMHA), pitting of Heinz bodies< |
Hard
to identify in cats and horses due to lack of central pallor in normal RBC’s
of these species |
Hereditary,
immuno-hemolytic anemia (acquired) |
Dacryocytes
(Teardrop) |
Drop
shaped, single elongated or pointed extremity, usually microcytic, hypochromic |
Fragmentation,
distortion of RBCs |
Myeloproliferative
disorders, glomerulonephritis (dog) |
Iron
deficiency anemia in ruminants (including llamas) |
Myelofibrosis,
anemia |
Drepanocytes
(Sickle cells) |
Fusiform,
spindle-shaped, crescent-shaped, or holly-leaf forms |
Develop
secondary to hemoglobin polymerization |
|
Normal
observation in deer and some species goats and sheep |
Sickle
cell disorders |
| Crystallized
Hemoglobin |
Presence
of rhomboidal, tetragonal, or rod-shaped hemoglobin crystals within erythrocytes |
Presence
of large crystals distorts the cell |
Nonpathological |
Occasionally
observed in blood smears of cats and llamas |
Post
splenectomy, hemoglobin related diseases |
References
1. Cowell RL, Tyler RD:
Diagnostic Cytology and Hematology of the Horse, 2nd ed. St. Louis, Mosby,
Inc., 2002.
2. Cowell RL, Tyler RD,
Meinkoth JH: Diagnostic Cytology and Hematology of the Dog and Cat, 2nd ed.
St. Louis, Mosby, Inc., 1999.
3. Harvey JW: Atlas of
Veterinary Hematology: Blood and Bone Marrow of Domestic Animals. Philadelphia,
WB Saunders Co., 2001.
4. Shah, Kalpesh. No date.
Poikilocytes. Peripheral Blood Smear Examination. Retrieved 10/21/02.
From http://WWW.kalpesh.itgo.com/PS9-1.htm.
5. University of Minnesota
Academic Health Center. 2/5/00. Morphological Abnormalities Associated with
Erythrocytic Series. Retrieved 10/21/02 From http://WWW.courses.ahc.umn.edu/medical-school/LaMP/5104/atlas/glossary.htm
6. Lee GR, Foerster J,
Lukens J, Paraskevas F, Greer JP, Rodgers GM (eds): Wintrobe's Clinical Hematology,
10th ed., vol. 1. Philadelphia, Lippincott Williams & Wilkins,
1999.
Acknowledgement
"Milk" © by Yoju, is from her website Watercolors
by Yoju and is used with permission of the artist. |