Red Blood Cell Abnormalities

Hypochromia – Hypochromia corresponds to a very thin rim of Hgb and a

larger center pale area. These red cells are often microcytic and are seen in iron
deficiency, thalassemias, and sideroblastic anemia

Microcytosis – (<6 micrometers in diameter) : Differential diagnosis includes

iron deficiency anemia, anemia of chronic disease, thalassemias, and
sideroblastic anemia. These cells are usually hypochromic and have prominent
central pallor.
Macrocytosis – (>9 micrometers in diameter) : Differential diagnosis includes
liver disease, alcoholism, aplastic anemia, and myelodysplasia. Megaloblastic
anemias (B12 and folate deficiencies) have macro-ovalocytes (large oval cells).
Reticulocytes are large immature red cells with polychromatophilia.

Schistocytes (fragmented cells): Schistocytes are caused by mechanical

disruption of cells in the microvasculature by fibrin strands or by mechanical
prosthetic heart valves. Differential diagnosis includes TTP/HUS, DIC, HELLP
Syndrome, and malignant hypertension.
Acanthocytes (speculated cells with irregular projections of varying length):
These are often seen with liver disease.

Crenated/Burr Cells (cells with short, evenly spaced cytoplasmic projections):

Crenated cells may be an artifact of slide preparation or found in renal failure
and uremia.

Bite Cells (cells with a smooth semicircle extracted): Bite Cells are due to
spleen phagocytes that have removed Heinz bodies consisting of denatured
Hgb. They are found in hemolytic anemia due to glucose-6-phosphate
dehydrogenase deficiency.

Spherocytes (round, dense cells with an absent central pallor): Spherocytes are
seen in immune hemolytic anemia and hereditary spherocytosis.

Sickle Cells (sickle-shaped cells): Sickle cells are due to polymerization of Hgb
S. This occurs from the substitution of a valine for glutamic acid as the sixth
amino acid of the beta globin chain, which produces a hemoglobin tetramer
(alpha2/beta S2) that is poorly soluble when deoxygenated. They are found in
sickle cell disease but not in sickle cell trait.

Target Cells (cells with extra hemoglobin in the center surrounded by a rim of
pallor; “bull’s eye appearance”): Target cells are due to an increase in the ratio
of cell membrane surface area to Hgb volume within the cell. They have a
central spot of Hgb surrounded by a ring of pallor from the redundancy in the
cell membrane. They are found in liver disease, post splenectomy, and in
hemoglobinopathies.

Teardrop cells/dacryocytes (teardrop-shaped cells): These are found in

myelofibrosis and myelophthisic states of bone marrow
Ovalocytes (elliptical cells): Ovalocytes are due to abnormal membrane
cytoskeleton found in hereditary elliptocytoisis.

Polychromatophilia (blue hue of cytoplasm): This is due to the presence of

RNA and ribosomes in reticulocytes.
Howell-Jolly bodies (small, single, purple cytoplasmic inclusions): These
represent nuclear remnant DNA and are found after splenectomy or with
functional asplenism.

Basophilic Stippling (dark-purple inclusions, usually multiple): Basophilic

stippling arises from precipitated RNA found in lead poisoning and thalassemia.

Nucleated red cells: These are not normally found in the peripheral blood. They
appear in hypoxemia and myelofibrosis or other myelophthisic conditions, as
well as with sever hemolysis.
Heinz bodies: (inclusions seen only on staining with violet crystal): Heinz
bodies represent denatured Hgb and are found in glucose-6-phosphate
dehydrogenase after oxidative stress
Parasites: A variety of parasites, including malaria and babesiosis, may be seen
with red blood cells
Rouleaux (red cell aggregates resembling a stack of coins): Rouleaux is due to
the loss of normal electrostatic charge-repelling red cells due to coating with
abnormal paraprotein, such as multiple myeloma.

Leukoerythroblastic smear (teardrop cells, nucleated red cells, and immature

white cells): This is found in marrow infiltration or fibrosis (myelophthisic
conditions).

Coagulation Cascade

Basic Coagulation Cascade