Abnormal Morphology of RBCs

Anisocytosis

variations in cell size

normal RDW < 15

normocytosis < 10% variation

quantitated as: 1+, 2+, 3+, or 4+

slight, moderate, marked

poikilocytosis

variations in cell shape

quantitate as:

• slight, moderate, marked

• 1+, 5-10/hpf

• 2+, 10-20/hpf

• 3+, >20/hpf

anisochromia

variations in cell color

reflects hemoglobin concentration

central pallor - should be approx the diameter of cytoplasmic staining

other variations in cell morphology

cell inclusions

variations in erythrocyte distribution

normocyte

diameter: 6-8 um

average = 7 um

Anuclear

Biconcave, discoid

central pallor - equal to diameter of stained area

MCV = 80-96 fl

MCH = 27 - 32 pg

MCHC = 32-36%

microcyte

Diameter < 6.0 um

MCV < 80 fl

MCH < 26 pg

increased central pallor

quantitated: slight, moderate, many

clinical significance: decreased Hb synthesis, Fe deficiency anemia-IDA, Thalassemia, anemia of chronic disease (ACD), sideroblastic anemia, lead poisoning

macrocyte

diameter is greater than 8.0 um

MCV > 96-100 fl

MCH > 32 pg

clinical implications:

• defect in nuclear/DNA maturation

  • B12 deficiency

  • Folic acid deficiency

• liver disease

• obstructive jaundice

• alcoholism

• chemotherapy

• reticulocytosis, erythropoiesis

classification of anemia based on RBC MCV

echinocytes

 Crenated RBCs, Burr Cells
 Short projections
 Evenly spaced

 Defects:
 Depletion of ATP
 Osmotic imbalances, physiologic loss of water
 Prolonged exposure to anticoagulant

 Clinical Implication:
 Uremia
 Chronic Renal disease
 Liver disease (Cirrhosis, Hepatitis)
 Renal failure
 Hypothyroidism, burns

Acanthocytes

 THORN, SPUR CELL
 Irregular spines protruding from RBC
surface
 Unevenly placed
 Decrease in cell volume

 Results:
 Alterations in membrane lipid content
 Loss of membrane integrity
 High cholesterol to phospholipid ratio

 Clinical Implications:
 Abetalipoproteinemia
 Liver disease
 Hemolytic anemia, post-splenectomy

Elliptocytes/Ovalocytes

 Elongated RBCs
 Rod or Cigar-Shaped
 Narrower than
ovalocytes
 Membrane defect in
spectrin and protein
4.1
 Normocytic
 Clinical Association:
 Hereditary elliptocytosis
 Thalassemia
 Fe Deficiency anemia

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 Egg-Shaped or oval-shaped
 Bipolar aggregates of Hb
 Normocytic or macrocytic
 Normochromic or
hypochromic
 Cause: Reduced ATP and
2,3 DPG
 Clinical Association:
 Megaloblastic anemia (macro sized ovalocytes)
 Myelodylsplastic syndromes
 Thalassemia (normocytic ovalocytes seen)

target cells/codocytes

flattened RBC

Hb concentration at center and periphery of cell

Resembles archery target

Membrane defect: excess membrane cholesterol and phospholipid, decreased Hb

implications:

• hemoglobinopathies - Hb C, Hb S, Hb SC

• thalassemia

• iron deficiency anemia

• liver disease, obstructive jaundice

• post-splenectomy

dacrocytes, tear drop cells

teardrop- pear shaped

rounded on one end

pointed on the other

results from squeezing during splenic passage

clinical significance:

• primary myelofibrosis (PM)

• B12 and folate deficiency

• ineffective erythropoiesis

• thalassemia

stomatocytes

 Round RBC
 Elongated, mouth-like central pallor.
 Caused by abnormally increased cation influx results in
increased permeability to sodium.
 Asymmetric increase in passive Na+ and K+
permeability
 Influx of Na+ exceeds the loss of K+
 Causing a net influx of water, overhydration, and
swelling

 Clinical Implications:
 Hereditary Stomatocytosis
 Acute Alcoholism
 Rh Null disease
 Liver disease, cirrhosis
 Glutathione deficiency
 Lead poisoning
 Artifact

schistocytes

 RBC Fragments
 Due to membrane damage
 Clinical Implications:
 Disseminated intravascular Coagulation (DIC)
 G6PD deficiency
 Hemolytic anemias
 Hemolytic uremic syndrome (HUS)
 Micro-angiopathic hemolytic anemia
 Prostheitc heart valves
 Burn patients
 ABO/RH incompatibility

bite cells

spheroid RBC with “bite-like” missing membrane

clinical implications: G-6-PD deficiency, hemolytic episodes, hemoglobinopathies

helmet cells, keratocytes

form of schistocytes

helmut shaped

implications - DIC, hemolytic anemia

spherocytes

 Very spheroid,
 Smaller in diameter
 Loss of biconcavity, no central pallor

 Genetic Membrane defect
 Defect in Spectrin assembly
 Poor Protein 4.1 to spectrin binding
 Actin-spectrin band 3 complex defect
 Results in defective cytoskeleton

 Higher concentration of hemoglobin per cell
 Increased MCHC > 36%

 Clinical Implications:
 Hereditary spherocytosis
 Immune Hemolytic anemia (Acute & chronic Extravascular)
 pseudo-spherocytes)
 Severe burns
 Post Splenectomy

drepanocytes

SICKLE CELLS
 Elongated RBCs
 Point projections on either end
 Cell may be straight or curved
 Presence of Hb S
 Produces a hemoglobin that crystalizes under low oxygen
tension conditions.
 Clinical Implications:
 Sickle cell anemia (disease or trait)
 Hb C/S disease
 Confirm by Dithionite solubility
 Hb electrophoresis

normochromic

Hb is normal

MCH is normal

MCHC is normal

Good central pallor

hypochromic

decreased Hb

decreased MCH

decreased MCHC

increased central pallor

clinical indications:

Fe deficiency anemia, thalassemia, anemia of chronic disease (ACD), lead poisoning, sideroblastic anemia

polychromatophilia

polychromasia

wright’s stain

increase in diffuse basophilic RBCs

cells are slightly immature

results from diffuse RNA

supravital stain, reticulocyte

quantitate as:

1+, 1-3/hpf

2+, 3-7/hpf

3+, >7/hpf

clinical significance of polychromasia

 Increased Polychromasia:
 Increased erythropoiesis
 Increased bone marrow production
 Associated with:
 Physiologic correction for Anemia
 Hemolytic anemia
 Response to treatment
 Not elevated in:
 untreated Fe deficiency or B12 Deficiency
anemia

basophilic stippling

Coarse granulation
 RNA and ribosome/mitochondrial aggregates
 Even distribution throughout RBC
 Visualized with Wright’s stain and Supravital stains

 Clinical Implications:
 Lead Intoxication
 Heavy metal poisoning
 Thalassemia
 Severe anemia
 Accelerated erythropoiesis
 Quantitate as: slight, moderate, marked

cabot rings

 Thread-like rings
 Loops or figure eights
 Single or Multiple rings
 Residual nuclear membrane or mitotic
spindle
 Visible with Wright’s stain
 Implications:
 Severe anemia
 Pernicious anemia (B12 deficiency)
 Lead Intoxication

howell jolly bodies

small, round, dark blue- purple masses

eccentric

nuclear DNA remnants

visible with wrights stain

cells may contain 1-2 HJ bodies

implications:

• pernicious anemia

• hemolytic anemia

  • sickle cell anemia

• post splenectomy

• thalassemia

• alcoholism

pappenheimer bodies

small blue granules

clusters of free iron. non-heme iron

near the periphery of RBC

visible with wright’s stain and prussian blue

confirm with prussian blue stain - stains iron, siderotic granules

clinical implications - sideroblastic anemia, severe hemolytic anemia, thalassemia, post splenectomy, B12, folate defic, sickle cell anemia

siderodic granules

when stained with Prussian blue

if granules are in non-nucleated cell - siderocyte

if granules are in NRBC - ringed sideroblast

malarial pigments

schuffner’s granules

granular pigments appearing in RBC’s parasitized by Plasmodium spp

fine red to pink granules

Plasmodium. Vivax and P. ovale infection

• P. falciparum and P. malaria are neg

• Visible with Wrigh’ts stain

• Mauer’s dots - P. falciparum and larger wedge shaped granules

Schuffner’s granules

P. vviax and P. ovale

Parasite rings

P. falciparum and P. malariae

Heinz Bodies

 Precipitated, denatured, unstable
Hemoglobin
 Visible with Supra vital stains
 Crystal violet
 Not visible with Wright’s stain

 Implications:
 (G6PD) deficiency
 Glucose-6-phosphate dehydrogenase
 Drug induced or food induced
 Unstable hemoglobin
 Alpha Thalassemia
 Hb-H, Barts, I

In G6PD deficiency

 G6PD protects Hb from oxidation
 Globin chains are denatured
 Forming Heinze bodies
 Heinze bodies attach to cell membrane
 induce membrane damage
 Bite cells and Schistocytes may be seen
 Alpha thalassemia: Presence of Hb-H (B4)

Favism

A potential fatal hemolytic episodes

following ingestion of fava beans

associated with G6PD deficiency

causes oxidation of unstable hemoglobin

appearance of bite cells

Hemoglobin C crystals

 Intra erythrocyte crystals
 Oblong hexagonal crystals
 Insoluble Hb-C
 Crystals are visible with Wright’s stain
 Implications:
 Hemoglobin CC, SC, CA disease

Staining characteristics in RBCs

Agglutination

 Aggregates or clumps
 Antibody induced
 Clinical Indicates:
 Cold agglutinins
 Autoimmune Hemolytic anemia
 Mycoplasma pneumoniae infections
 Falsely affects electronic cell counting:
 Decreases RBC count
 Increases MCV

 Corrected by warming the specimen @ 37 C for 15
minutes.

Rouleaux

stacking of RBCs

Increased plasma proteins

decreased zeta potential - natural repulsion mechanism

creates the stack of coins effects

examine on “high dry” or 40x

clinical association - multiple myeloma

quantitate as - slight, moderate, marked