Anisocytosis Information and Courses from MediaLab, Inc.

Jaundice was recognized in a day-old infant. Notice particularly the size variation (anisocytosis) of the erythrocytes on the infant's peripheral smear. What does this observation mean? Does it provide immediate information that might serve as guidance in expediting diagnosis and treatment? Note that normal-sized red blood cells, microcytes, microspherocytes, macrocytes, and nucleated red blood cells are all present. Red cell variations are expected findings in healthy neonates, but the variations here are exaggerated. Hyposplenic functional features may appear, including acanthocytes, spherocytes, and possibly Howell-Jolly bodies, especially if hemolysis is particularly vigorous. A high (3-7%) reticulocyte count is not unusual during the first three or four days after birth, however, the marrow in this jaundiced infant is proliferating vigorously in response to hemolysis. A call for more red cells is urgent. Immature red cells (in the form of nucleated red cells) and red cells with stippling of RNA (basophilic stippling) are readily identified. Red cell maturation sequence has not been totally processed in the marrow nor is all residual red cell debris removed by the spleen. In the lower photograph are reticulocytes stained by supravital stain (new methylene blue). Basophilic stippling (specks of RNA) stains with both supravital stains and with routine Wright-Giemsa stain.

A 49-year-old male with pneumonia was treated with penicillin. He became jaundiced with yellow sclera. Observe the photograph of his peripheral blood smear. Anisocytosis was observed with pale-centered microcytes and polychromatophilic macrocytes. Since penicillin is a classic offender for autoimmune hemolytic disease, the clinician asked for an antihuman globulin (AHG) test, also known as the Coombs test. A positive AHG reaction occurs when the antibody stimulated by penicillin becomes attached to red blood cells. Hemolysis follows, leaving the patient with jaundice and a peripheral blood smear, as demonstrated in the photograph.

The patient whose blood smear is shown in the photograph was a 32-year-old female from Virginia who came to the high country of Colorado to ski. The day after arrival, she experienced shortness of breath, fatigue, and upper abdominal pain. She was seen in a medical center in the mountains where a working diagnosis of altitude sickness was made. A CBC revealed RBCs 5.1 x 1012/L, hemoglobin 12.8g/dL, MCV 60fL, hematocrit 40.9%, and normal total WBC, differential, and platelet count. The RDW was normal. Further questioning revealed a previous diagnosis of heterozygous beta-chain thalassemia. No other abnormal hemoglobins were found on hemoglobin electrophoresis, but HbA-2 was elevated to 5%, supporting the diagnosis of beta thalassemia. The patient's poikylocytosis and anisocytosis may be a clue to an underlying erythrocyte abnormality. Persons with iron deficiency anemia may experience various degrees of hypoxia upon arriving at high altitudes. Those with sickle cell disease and thalassemia minor (as in this case) may experience bone pain or other symptoms of "crisis" and/or alteration in the appearance of their erythrocytes upon sudden high altitude exposure. The classic teaching is that in differentiating iron deficiency anemia from thalassemia, increased RDW would favor iron deficiency; normal RDW favors thalassemia.

Many of the distorted erythrocytes displayed on the previous page are also present on this one. We see anisocytosis, poikilocytosis, fragmented forms, target cells, and a few Howell-Jolly bodies. Note also circulating nucleated red blood cells (normoblasts). The presence of these normoblasts may represent a premature release from a hyperplastic marrow or, more likely, are due to a lessening of the normal inhibition of erythroid release from the marrow as a result of splenectomy, permitting their earlier entry into the circulation.

Anisocytosis is a general term used to describe increased variation in size of the red cell population present on a blood smear. The normal size of red cells varies from approximately 6 to 9 microns. Notice that normal, small and large cells can be seen in this field. Since several populations of cells are present, this abnormality will not be reflected in the MCV value (However, it will show up as an increase in the RDW, which is a measure of red cell size variation.) As the severity of the anemia increases, the amount of significant anisocytosis present also increases.