Erythrocytes

Red cell indices reported on a full blood exam may include:

Red cell indices essentially describe:

How much haemoglobin there is
How many cells the haemoglobin is distributed into

Haemoglobin
Concentration of haemoglobin in blood.
- Indicator of oxygen carrying capacity
Haematocrit
Proportion of blood volume made up of erythrocytes.
- Usually ~3x the haemoglobin
Red cell count
Number of cells per microlitre.
MCV
Average volume of individual erythrocytes.
- Classifies anaemia into microcytic, macrocytic, or normocytic
MCH
Average amount of haemoglobin per erythrocyte.
MCHC
Average concentration of haemoglobin in red cells.
Red cell histogram
Graphical display of variation in erythrocyte volume.
RDW
Measure of variation in erythrocyte volume, calculated from the width of the histogram at 1 SD from the mean, divided by the MCV.

Abnormalities

Abnormal findings include:

Some abnormal findings are specific to blood smears, others are detected on automated analysers.

Splenic macrophages remove damaged and abnormal erythrocytes from circulation; asplenic patients may therefore accumulate a significant number of the more abnormal forms that are produced in small numbers in health.

Macrocytosis (Normal: 80-10 fL)
Enlarged erythrocytes, occurring usually due to abnormal development or membrane composition. Causes are divided into:
- Common:
  - Vitamin B₁₂ deficiency
  - Folate deficiency
  - Alcoholism
  - Myelodysplasia
- Uncommon
  - Reticulocytosis
  - Liver disease
  - Hypothyroidism
  - Multiple myeloma
  - Aplastic anaemia
  - Leukaemia
  - Drugs

Dimorphic population
Bimodal distribution of erythrocyte cell volume on a red cell histogram. Usually occurs due to:
- Normocytic normochromic cells that existed either prior to disease onset or after treatment
- Microcytic hypochromic cells that existed either prior to (e.g., iron infusion) or after (e.g. myeloablation) treatment

Sickle Cell
Erythrocyte deformed by HbS which has polymerised under hypoxic stress. Diagnostic of sickle cell disease.

Sickle cell disease is covered under Sickle Cell Disease.

Reticulocytosis (Normal: 0.5-2.5%)
Juvenile erythrocytes that contain RNA remnants and ribosomes but no nucleus, ejected into circulation in response to anaemia.

Schistocytes
Fragmented, irregular, jagged erythrocytes formed by mechanical destruction during haemolysis.

Nucleated erythrocytes (Normoblastaemia)
Circulating erythrocyte precursors that have yet to eject their nucleus, indicating either:
- ↓ DO₂
  Release of immature red cells to try and add some additional oxygen carrying capacity. Causes include:
  - Hypoxaemia
  - Anaemia
    Any cause.
- Hyposplenism
  Normoblasts are normally removed in the spleen.
  - Hyposplenism
  - Malaria
  - Sickle cell anaemia
  - Physiologic
    3-10 normoblasts per 100 WBC are normal at birth.
- Bone marrow stress
  Upregulation of bone-marrow production, overwhelming capacity of spleen for elimination.
  - Bone marrow destruction
    - Haematological malignancy
    - Bony metastases
    - Histiocytosis
    - Sarcoidosis
  - Extramedullary haematopoiesis
    - Chronic haemolysis
    - Polycythaemia vera
- Multifactorial
  - Sepsis
  - Uraemia
  - Liver disease
  - DKA
  - IBD
  - Burns
  - Chemotherapy

Hyperviscosity syndrome describes impaired blood flow and organ perfusion due to ↑ blood viscosity, which occurs due to ↑ concentration of cells or macromolecules, and is characterised by:

Hypervolaemia
Visual disturbances
Neurological dysfunction
Coma, seizures.

Rouleaux Formations
Reversible agglutination of erythrocytes in a stack or coin-like formation, which may occur due to:
- ↑ Plasma protein (but not albumin)
  - Multiple myeloma
- Inflammation
  - Malignancy
  - Infection
  - Inflammation
- ↑ Blood viscosity
  - Hyperviscosity syndromes
  - Dehydration

Target Cells
Erythrocyte with a disproportionate amount of membrane to haemoglobin, and is:
- Common in:
  - Thalassaemia
  - Jaundice
  - Post-splenectomy
- Uncommon in:
  - Sickle cell anaemia
  - Iron deficiency

Spherocytosis
Erythrocyte with a disproportionate amount of haemoglobin to membrane, resulting in distortion of the biconcave disk to a spherical shape with a greater volume-to-surface area ratio. Causes include:
- Haemolytic anaemias
- Hereditary spherocytosis

Howell-Jolly Bodies
Erythrocyte containing DNA remnants, which occur with:
- Post-splenectomy
- Haemolysis
- Megaloblastic anaemia
- Macrocytosis
- Corticosteroids
- Pernicious anaemia

Heinz Bodies (Heinz-Ehrlich bodies)
Erythrocyte containing denatured haemoglobin, indicating oxidative stress due to:
- Toxins
  - Quinidine
  - Primaquine
- Unstable haemoglobin form
  - α-thalassaemia
  - Methaemoglobinaemia
- Damaged RBC metabolism
  - G6PD
  - Bactrim toxicity

The pathology of methaemoglobinaemia is covered under Methaemoglobinaemia.

Basophilic Stippling
Erythrocyte with small blue-staining granules consisting of aggregated ribosome and ribosomal RMA fragments. Associated with:
- Lead poisoning
  Prevents degradation of ribosomal RNA. Causes include:
  - Post GSW
  - Adulterated drugs
    Classically opium.
  - Contaminated herbal medications
- Heavy metal poisoning

References

Constantino BT. The Red Cell Histogram and The Dimorphic Red Cell Population. Laboratory Medicine. 2011;42(5):300-308. doi:10.1309/LMF1UY85HEKBMIWO
Constantino BT, Cogionis B. Nucleated RBCs—Significance in the Peripheral Blood Film. Laboratory Medicine. 2000;31(4):223-229. doi:10.1309/D70F-HCC1-XX1T-4ETE
Sanchez JR, Lynch DT. Histology, Basophilic Stippling. In: StatPearls. StatPearls Publishing; 2023. Accessed August 7, 2023.