View source for Red Blood Cell Morphology

== Size, Shape & Arrangement ==
{| class="wikitable"
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!RBC Trait
!Appearance
!Physiology
!Associated Conditions
!Follow-up Testing
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|Rouleaux
|Stacked formation ("stack of coins") in monolayer

* Often seen with blue background staining
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* Increased amount of plasma proteins
* Excess protein have + charge that reduces RBC membrane charge (zeta potential)
* Reduced charge allows cells to stack (due to biconcave shape)
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* Multiple myeloma/plasma cell myeloma
* Chronic liver disease
* Lymphomas
* Acute and chronic inflammatory diseases (especially when plasma proteins like fibrinogen or globulins are increased)
|Saline replacement to remove excess protein
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|Agglutination
|Irregular clumping of cells in monolayer
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* Caused by IgM antibodies (cold agglutinins)
* Large antibodies can span zeta potential gaps and form lattice with other antibody-coated cells
* IgMs bind to RBCs at room temperature
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* Cold autoimmune hemolytic anemia
* IgM-associated lymphomas
* Multiple myeloma
* Paroxysmal cold hemoglobinuria
|Pre-warm sample to 37C to dissociate cold IgMs
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|Microcytosis
|Smaller cells (round, biconcave)
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* More divisions causing smaller cells
* Hemoglobin errors - cells continue dividing to reach adequate hemoglobin concentrations
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* Thalassemia (small, uniform size - N RDW)
* IDA (small, varying size - ↑ RDW)
* Anemia of chronic inflammation
* Lead poisoning
* Hemoglobinopathies
* Sideroblastic anemia
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| rowspan="2" |Macrocytosis
|Round macrocytes (size)
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* Increases in cell membrane size (more cholesterol)
* Retain shape, but with larger membrane
|Moderate ↑ MCV

* Liver disease
* Normal neonate
* Reticulocytosis
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|Oval macrocytes (shape)
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* Fewer divisions causing larger cells - errors in DNA synthesis
* Cytoplasm increases, but DNA doesn't (asynchrony)
|Marked ↑ MCV

* Megaloblastic anemia (B12/folate deficiency)
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|Hypochromasia
|Cells >1/3 central pallor

* 1/2-2/3 moderate
* >3/4 marked
* Consistent field-to-field, gradual colour change
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* Decreased or abnormal hemoglobin
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* IDA
* Thalassemias
* Sideroblastic anemia
* Lead poisoning
* Some anemia of chronic inflammation
|↓ MCH, ↓ MCHC
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|Increased polychromasia
|Larger, irregular bluish cells, without central pallor
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* Cells at final stage of RBC maturation
* Have lost nucleus but have not assumed final biconcave shape
* Increase indicates bone marrow response to push out immature cells (compensatory mechanism)
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* 0.5-2.5% normal in adults
* Increased in conditions causing RBC damage or destruction
|Reticulocyte count

* Manual supravital staining (methylene blue to visualize RNA)
* Automated immature reticulocyte fraction (IRF) to stain nucleic acids
|}

== Poikilocytosis ==
NOTE: be careful when distinguishing poikilocytosis from artifacts.
{| class="wikitable"
!RBC Trait
!Appearance
!Physiology
!Associated Conditions
!Follow-up Testing
|-
|Sickle Cells (Drepanocytes)
|'''Hemoglobin S'''
Elongated cells with pointed ends; may be curved

* Dark red/pink, without central pallor


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* Cells carry mutated globin chains (hemoglobin S)
* When O2 is low, hemoglobin S polymerizes and forms long fibre 'crystals' that distort cell shape
* Repeated sickling permanently alters cell
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* Sickle cell disease or anemia
* Sickle cell trait
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* Sickle cell solubility test
* Hemoglobin electrophoresis
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|Hemoglobin SC
|'''Hemoglobin SC'''
* Mitten/gloved hand shape
|Cells carry mutated globin chains for both hemoglobin S and hemoglobin C
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* Hemoglobin SC disease
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|Hemoglobin C
|'''Hemoglobin C'''
* Gold bar (dense, rounded rectangle)
|Cells carry mutated globin chains (hemoglobin C)
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* Hemoglobin C disease
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|Oval Macrocytes
|Oval macrocytes
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* Fewer divisions causing larger cells - errors in DNA synthesis
* Unable to synthesize DNA due to vitamin deficiency
* Cytoplasm increases, but DNA doesn't duplicate so cell doesn't divide (asynchrony)
|Marked ↑ MCV (>80 fL)

* Megaloblastic anemia (B12/folate deficiency)
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|-
| rowspan="2" |Spherocytes
|'''Spherocytes'''
Small, dense, dark, round cells without central pallor
| rowspan="2" |
* RBCs lose portions of membrane during circulation
** Intrinsic abnormalities
** Immune hemolysis
** Fibrin strands
** Thermal injury
* Damage to membrane results in smaller cell size, becoming more spheroid
* Hemoglobin concentrated in smaller cell
| rowspan="2" |↑ MCHC (>360 g/L)

* Hereditary spherocytosis
* Hemolytic anemias
* Transfused cells (during storage)
* Severe burns
| rowspan="2" |
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|'''Microspherocyte'''
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|Target cells (codocytes)
|Cells appear with bull's eye in centre
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* Relative increase in RBC surface membrane
** Loss of hemoglobin reducing volume
** Excess membrane cholesterol/phospholipid
|Macrocytic

* Liver disease

Normocytic

* Hemoglobin disorders (sickle cell, HGB C or E)

Microcytic

* IDA
* Thalessemia
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| rowspan="2" |Ovals/Pencils
|Ovalocytes
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|Elliptocytes (Pencils)
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|Teardrop Cells
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|Acanthocytes (Spur cells)
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|Echinocytes (Burr cells)
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|Stomatocytes
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|Schistocytes (fragments)

* Schistocytes
* Helmet cells
* Bite cells
* Blister cells
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== RBC Inclusions & Early Cells ==

=== Visible by normal staining ===
{| class="wikitable"
!RBC Trait
!Appearance
!Physiology
!Associated Conditions
!Follow-up Testing
|-
|Howell-Jolly bodies
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|DNA
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|Pappenheimer bodies
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|Iron
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|Basophillic stippling
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|RNA
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|NRBCs
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=== Supravital staining ===
{| class="wikitable"
!RBC Trait
!Stain
!Appearance
!Physiology
!Associated Conditions
!Follow-up Testing
|-
|Heinz bodies
|New methylene blue
|Purple-blue inclusions around inner membrane (may be one or multiple)
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* Normal hemoglobin denatured by oxidative stress
* Abnormal, unstable hemoglobin precipitates out
* Removal of Heinz bodies by spleen causes bite cell formation (HBs don't deform when passing through spleen)
|Associated with bite or blister cells

* G6PD deficiency
* Abnormal or unstable hemoglobin
* Oxidant drugs or chemicals
* Some hemoglobinopathies
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|Hemoglobin H
|Brillian Cresyl Blue
|Small, evenly dispersed blue-purple granules

* Golf ball/raspberry appearance
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* Deletion of alpha-globin genes causes formation of beta-chain tetramers
* Abnormal hemoglobin H
* Hemoglobin H susceptible to oxidation, resulting in denaturation - forms precipitate
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* Hemoglobin H disease (alpha thalassemia)
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|Reticulocytes
|New methylene blue
|Groups of blue-coloured inclusions in cell
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* RNA present in less mature cells precipitates
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* Various (increased erythrocyte production)
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|}

== Combinations of Morphology ==
{| class="wikitable"
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|Dual Population
|Usually normal population with abnormal population
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* Condition being treated (newer, healthy population)
* Condition plus blood transfusion
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|Normocytic/normochromic
|Normal size and colour of RBC
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* Normal patient
* Anemia from reduced RBC numbers (hemorrhage, burns, etc.)
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|Hypochromic/microcytic
|Small cells with large central pallor
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* Anemia from abnormal hemoglobin production or metabolism (e.g., IDA)
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RBC Metabolism

RBC Breakdown

Extravascular Hemolysis (Macrophage-Mediated Hemolysis)

* Occurs in spleen, primarily due to splenic macrophages
* Slower movement through splenic sinusoids allows older or damaged cells to be destroyed
* RBC contents salvaged and metabolized
** Hemoglobin broken down into globin chains and iron
**
* Most (90%) of RBCs are destroyed this way

Intravascular Hemolysis (Fragmentation/Mechanical Hemolysis)

* Occurs inside blood vessels
* Mechanical damage to cells causing hemolysis
** Can also be caused by damage to blood vessels (e.g., clots)
* RBC contents also salvaged
** Hemoglobin binds to transport proteins (primarily haptoglobin when available, if hemoglobin oxidizes then binds to hemopexin)
** Taken to liver (hemoglobin) or excreted by kidney
* Less common (10-20%) method of RBC destruction