Morphology — Definitions, Clinical Conditions & Cell Pictures

Revised morphology review with focused cards for appearance, causes, and clinical conditions. Objectives 1–11 use the lecture; objective 12 includes matching cell pictures. Missing images: ASH Image Bank (Vicari, Scordino, Schrier, Maslak) and CDC DPDx case 287 (University of Texas HSC).

Anisocytosis — definition

Variation in RBC size.

Poikilocytosis — definition

Variation in RBC shape.

Normochromic — definition

Normal RBC coloration, with central pallor about 2–3 microns across.

Hypochromic — definition

Increased central pallor, greater than 3 microns. MCHC helps assess hypochromia.

Normal RBC — size

About 7–8 microns in diameter. Normal size variation is about 5%.

Normal RBC — membrane proteins

Glycophorin and spectrin.

RBC maturation — main changes

The cell loses its nucleus, becomes smaller, and changes cytoplasmic color as it matures.

RBC morphology — how much of the smear should be reviewed?

At least 10 oil-immersion fields. Check that abnormalities are consistent and not artifacts.

RBC morphology — which indices should be reviewed?

MCV, MCH, MCHC, and RDW.

Anisocytosis and poikilocytosis — slight to 2+ grading

Slight: 5–10% of cells. 1+: more than 10–25%. 2+: more than 25–50%.

Anisocytosis and poikilocytosis — 3+ and 4+ grading

3+: more than 50–75% of cells. 4+: more than 75%.

Normal RBC — appearance

Reddish with Wright’s stain, with a central pale area about 2–3 microns across.

Macrocytic cells — associated conditions and processes

Impaired DNA synthesis; increased erythropoiesis with early reticulocyte release; increased membrane cholesterol and lecithin. Megaloblastic processes may produce macro-ovalocytes or macro-teardrops. Sideroblastic anemia can include macrocytes in a mixed-size population.

Microcytic cells — clinical conditions

Iron deficiency; thalassemic conditions; sideroblastic anemia; anemia of chronic disease; lead poisoning.

Mixed-size RBC population — associated anemia

Sideroblastic anemia can produce a dimorphic blood picture containing macrocytic, normocytic, and microcytic cells.

Macrocytosis — why does impaired DNA synthesis enlarge RBCs?

Fewer cell divisions occur, so the resulting cells are larger.

Macrocytosis — why can increased erythropoiesis cause it?

Reticulocytes or diffusely basophilic erythrocytes enter circulation prematurely.

Microcytosis — why does defective hemoglobin synthesis make cells smaller?

The cells undergo more divisions, producing a microcytic, hypochromic blood picture.

Microcytosis — iron and globin problems

Ineffective iron absorption, release, or utilization; decreased or defective globin synthesis.

Macrocytes — features to assess

Oval or round shape; red or blue color; central pallor; inclusions; and the reason for the size change.

Hypochromia — clinical conditions

Iron-deficiency anemia is specifically associated with hypochromia. Defective hemoglobin synthesis produces a microcytic, hypochromic picture.

Hypochromia — can it occur in different cell sizes?

Yes. Microcytic, normocytic, and macrocytic cells can be hypochromic. Target cells are included in the macrocytic hypochromic category.

Pseudohypochromia — definition and cause

Artificially induced pallor caused by water artifact. The pale area is distinctly outlined.

Hypochromia — 1+ and 2+ grading

1+: central pallor occupies half the cell diameter. 2+: central pallor occupies two-thirds.

Hypochromia — 3+ and 4+ grading

3+: central pallor occupies three-fourths of the cell diameter. 4+: only a thin rim of hemoglobin remains.

Polychromasia — definition and appearance

Immature RBCs enter peripheral blood and appear gray-blue rather than red.

Polychromasia — cause of the blue color

Residual RNA produces basophilia.

Polychromasia — associated process

Increased erythropoiesis with premature release of reticulocytes or diffusely basophilic erythrocytes.

Polychromatophilic macrocytes — cell type and confirming stain

They are reticulocytes. Methylene blue supravital staining demonstrates the reticular material.

Polychromasia — slight to 2+ grading

Slight: 1% of RBCs. 1+: 3%. 2+: 5%.

Polychromasia — 3+ and 4+ grading

3+: 10% of RBCs. 4+: more than 11%.

Target cell — name and appearance

Also called a codocyte. A target-like cell with increased surface membrane; bell shaped in three dimensions and hypochromic.

Target cell — primary defect or cause

Excess membrane cholesterol and phospholipids, or decreased cellular hemoglobin. Osmotic fragility is decreased.

Target cell — clinical conditions

Hgb C disease; Hgb C trait; post-splenectomy; liver disease; iron-deficiency anemia; other Hgb abnormalities.

Spherocyte — name and appearance

Small, round cell with no central pallor and a low surface-area-to-volume ratio.

Spherocyte — primary defect or cause

Membrane loss causes an irreversible shape change. Hereditary spherocytosis involves decreased spectrin quantity and function.

Spherocyte — clinical conditions

Immune hemolytic anemia; hereditary spherocytosis; post-transfusion.

Ovalocyte — name and appearance

Egg-shaped RBC. The picture shows macro-ovalocytes, the enlarged oval form.

Ovalocyte — clinical conditions

Myelodysplastic syndrome; thalassemic syndromes; megaloblastic processes. Ovalocytes may be macrocytic.

Elliptocyte — name and appearance

Elongated, pencil-shaped RBC.

Elliptocyte — primary defect or cause

Hereditary elliptocytosis involves a membrane defect in spectrin and other membrane protein that may cause hemolysis.

Elliptocyte — clinical conditions

Iron-deficiency anemia; hereditary elliptocytosis; idiopathic myelofibrosis.

Ovalocytes and elliptocytes — terminology

Ovalocytes are egg shaped; elliptocytes are pencil shaped. Some sources use the terms interchangeably.

Stomatocyte — name and appearance

RBC with a slit-like area of central pallor on an air-dried smear.

Stomatocyte — primary defect or cause

The change can be reversible. Chemical agents and artifact can produce the appearance.

Stomatocyte — clinical conditions

Artifact; hereditary spherocytosis; hereditary stomatocytosis; acute alcoholism; Rh null phenotype.

RBC fragmentation — main mechanism

Loss of membrane. Abnormal fluid circulation or an intrinsic RBC defect makes cells less deformable and promotes fragmentation.

RBC fragments — named forms

Schistocytes; burr cells; helmet cells (keratocytes); bite cells (degmacytes).

Schistocyte — name and appearance

A tiny, irregular RBC fragment.

Schistocyte — primary defect or cause

RBC fragmentation due to abnormal circulation or an intrinsic RBC defect, with reduced deformability and membrane loss.

Schistocyte — clinical conditions

Microangiopathic hemolytic anemia; disseminated intravascular coagulation; heart valve surgery; hemolytic uremic syndrome; thrombotic thrombocytopenic purpura; burns.

Echinocyte — name and appearance

Burr cell with multiple short, evenly spaced projections and retained central pallor.

Echinocyte — primary defect or cause

May be an artifact of smear preparation or storage; crenated cells can resemble true burr cells.

Echinocyte — clinical conditions

Uremia; heart disease; stomach cancer; peptic ulcer; post-heparin injection; hypothyroidism; dehydration; azotemia.

Agglutination — name and appearance

RBCs aggregate into irregular clusters.

Agglutination — primary defect or cause

RBC antibodies react with RBC antigens. Cold-related agglutination can occur at room temperature and disappear on warming.

Agglutination — clinical conditions

Cold antibody syndromes, including cold hemagglutination disease and paroxysmal cold hemoglobinuria.

Rouleaux — name and appearance

RBCs arranged in stacks resembling coins.

Rouleaux — primary defect or cause

Increased plasma globulins or fibrinogen, with protein deposition or adsorption on RBC membranes. Associated with a high ESR.

Rouleaux — clinical conditions

Multiple myeloma; Waldenstrom’s macroglobulinemia; chronic inflammatory disorders.

Agglutination — definition and cause

Clustering of RBCs caused by antibody reacting with RBC antigen.

Agglutination — associated conditions and warming response

Cold antibody syndromes. Clumping present at room temperature may disappear when the specimen is warmed.

Rouleaux — definition and cause

Stacks of RBCs resembling coins, associated with increased plasma globulins or fibrinogen.

Rouleaux — clinical conditions

Multiple myeloma; Waldenstrom’s macroglobulinemia; chronic inflammatory disorders.

Rouleaux — effect of saline dilution

The stacks disappear with saline dilution.

Howell-Jolly body — name and appearance

A small, round, dark-purple inclusion. Usually single or double and eccentrically located.

Howell-Jolly body — primary defect or cause

A remnant of nuclear DNA.

Howell-Jolly body — clinical conditions

Splenectomy; thalassemia; hemolytic anemia; megaloblastic anemia; functional hyposplenia.

Basophilic stippling — name and appearance

Multiple small blue-purple stipples dispersed within an RBC.

Basophilic stippling — primary defect or cause

Ribosomal material: ribonucleoprotein (RNA) and mitochondrial remnants.

Basophilic stippling — clinical conditions

Lead intoxication; thalassemia; disturbances of heme synthesis.

Pappenheimer bodies — name and appearance

Small, irregular magenta inclusions near the RBC periphery, often in clusters.

Pappenheimer bodies — primary defect or cause

Iron-containing material. Wright-stained inclusions are called Pappenheimer bodies; Prussian blue confirms iron and demonstrates siderotic granules.

Pappenheimer bodies — clinical conditions

Sideroblastic anemia; hemochromatosis or hemosiderosis; sickle-cell or thalassemic hemoglobinopathies; splenectomy.

Cabot ring — name and appearance

A delicate ring or figure-eight structure, sometimes resembling beads on a necklace, in a stippled RBC.

Cabot ring — primary defect or cause

The inclusion contains arginine-rich histone and non-hemoglobin iron.

Cabot ring — clinical conditions

Megaloblastic anemia; homozygous thalassemia; post-splenectomy.

Howell-Jolly bodies — material and location

DNA remnants, present singly or doubly in an eccentric position.

Howell-Jolly bodies — clinical conditions

Splenectomy; thalassemia; hemolytic anemia; megaloblastic anemia; functional hyposplenia.

Heinz bodies — definition and effect

Denatured or precipitated hemoglobin that becomes rigid and distorts the RBC membrane.

Heinz bodies — useful stains

May not be visible with Wright’s stain. Crystal violet and brilliant cresyl blue may demonstrate them.

Heinz bodies — clinical conditions

Alpha-thalassemic syndromes; G6PD deficiency; chemical insult to RBCs.

Acanthocyte — name and appearance

A smaller RBC with 3–12 irregular spicules.

Acanthocyte — primary defect or cause

Increased membrane cholesterol and surface area with decreased lecithin. Lecithin-cholesterol acyltransferase deficiency can increase cholesterol and produce acanthocytes.

Acanthocyte — clinical conditions

Severe hepatic disease; alcohol intoxication (Zieve’s syndrome); pyruvate kinase deficiency; congenital abetalipoproteinemia; vitamin E deficiency; post-splenectomy.

Teardrop cell — name and appearance

A pear-shaped RBC with a tail.

Teardrop cell — primary defect or cause

Distortion into a pear shape with a tail; associated with inclusion-body formation and myelofibrosis.

Teardrop cell — clinical conditions

Idiopathic myelofibrosis with myeloid metaplasia; thalassemia syndromes; iron deficiency; drug-induced Heinz body formation; other inclusion-body conditions; megaloblastic processes with macro-teardrops.

Drepanocyte (sickle cell) — name and appearance

Rigid, inflexible RBC with a pointed projection or sickle shape.

Drepanocyte (sickle cell) — primary defect or cause

Low oxygen causes hemoglobin tubules to form and bundle, deforming the cell. Repeated episodes can make the sickling irreversible.

Drepanocyte (sickle cell) — clinical conditions

Sickle-cell disease. With sickle-cell trait, sickled cells are usually absent from the routine smear.

Sickle cells — can the shape reverse?

Some return to their usual shape with oxygen; repeated sickling episodes can produce irreversibly sickled cells.

Malaria — name and appearance

Plasmodium parasites within RBCs. This Wright-stained example shows delicate ring forms with small chromatin dots in normal-sized RBCs; some are at the cell edge.

Malaria — primary defect or cause

Plasmodium infection of RBCs. The pictured example is Plasmodium falciparum.

Malaria — clinical conditions

Malaria. This example is falciparum malaria; the ring appearance is a parasite finding, not an RBC nuclear remnant.

Normal platelet — morphology

Small and round, with blue granules throughout light-blue cytoplasm.

Abnormal platelet — possible appearances

Agranular, large, tailing, or streaming platelets.

Abnormal platelet morphology — clinical conditions

Variations occur in idiopathic myelofibrosis. Large platelets occur with increased platelet turnover, idiopathic thrombocytopenia purpura, and bleeding.

Toxic leukocyte changes — associated conditions

Severe infection, inflammatory conditions, and leukemoid reactions may show toxic granulation, toxic vacuolization, or Döhle bodies.

Toxic granulation — appearance and contents

Large granules scattered through the cytoplasm of segmented neutrophils. They contain peroxidase and acid hydrolases.