Erythrocyte (RBC) Morphology

• Normal: 7.5 µm diameter. Roughly the size of the nucleus of a small lymphocyte.
• Reticulocytes (Wright's stain): large, grayish-blue, admixed with pink (polychromasia).
• Anisocytosis: variation in RBC size; large cells imply delay in erythroid precursor DNA synthesis caused by folate or B₁₂ deficiency or drug effect; small cells imply a defect in hemoglobin synthesis caused by iron deficiency or abnormal hemoglobin genes. The automated red cell distribution width (RDW) is a measure of anisocytosis.
• Poikilocytosis: abnormal RBC shapes; the following are examples:
  1. Acanthocytes (spur cells): irregularly spiculated; abetalipoproteinemia, severe liver disease, rarely anorexia nervosa.
  2. Echinocytes (burr cells): regularly shaped, uniformly distributed spiny projections; uremia, RBC volume loss.
  3. Elliptocytes: elliptical; hereditary elliptocytosis.
  4. Schistocytes (schizocytes): fragmented cells of varying sizes and shapes; microangiopathic or macroangiopathic hemolytic anemia.
  5. Sickled cells: elongated, crescentic; sickle cell anemias.
  6. Spherocytes: small hyperchromic cells lacking normal central pallor; hereditary spherocytosis, extravascular hemolysis as in autoimmune hemolytic anemia, G6PD deficiency.
  7. Target cells: central and outer rim staining with intervening ring of pallor; liver disease, thalassemia, hemoglobin C, and sickle C diseases.
  8. Teardrop cells: myelofibrosis, other infiltrative processes of marrow (e.g., carcinoma).
  9. Rouleaux formation: alignment of RBCs in stacks; may be artifactual or due to paraproteinemia (e.g., multiple myeloma, macroglobulinemia).

RBC Inclusions

• Howell-Jolly bodies: 1-µm-diameter basophilic cytoplasmic inclusion that represents a residual nuclear fragment, usually single; asplenic pts.
• Basophilic stippling: multiple, punctate basophilic cytoplasmic inclusions composed of precipitated mitochondria and ribosomes; lead poisoning, thalassemia, myelofibrosis.
• Pappenheimer (iron) bodies: iron-containing granules usually composed of mitochondria and ribosomes resemble basophilic stippling but also stain with Prussian blue; lead poisoning, other sideroblastic anemias.
• Heinz bodies: spherical inclusions of precipitated hemoglobin seen only with supravital stains, such as crystal violet; G6PD deficiency (after oxidant stress such as infection, certain drugs), unstable hemoglobin variants.
• Parasites: characteristic intracytoplasmic inclusions; malaria, babesiosis.

Leukocyte Inclusions and Nuclear Contour Abnormalities

• Toxic granulations: dark cytoplasmic granules; bacterial infection.
• Döhle bodies: 1- to 2-µm blue, oval cytoplasmic inclusions; bacterial infection, Chédiak-Higashi anomaly.
• Auer rods: eosinophilic, rodlike cytoplasmic inclusions; acute myeloid leukemia (some cases).
• Hypersegmentation: neutrophil nuclei contain more than the usual 2-4 lobes; usually >5% have ≥5 lobes or a single cell with 7 lobes is adequate to make the diagnosis; folate or B₁₂ deficiency, drug effects.
• Hyposegmentation: neutrophil nuclei contain fewer lobes than normal, either one or two: Pelger-Hüet anomaly, pseudo-Pelger-Hüet or acquired Pelger-Hüet anomaly in acute leukemia.

Platelet Abnormalities

• Platelet clumping: an in vitro artifact-is often readily detectable on smear; can lead to falsely low platelet count by automated cell counters.
• Giant platelets: can be a sign of a very young platelet or increased platelet production or abnormal karyocyte maturation; if the platelets are >5-6 µm in diameter, they may not be counted as platelets by electronic counters.