Erythrocyte morphology: Getting the most from your blood smear

Carolyn Grimes, DVM, DACVP (Clincal Pathology)
Regional Clinical Laboratory Director, Ethos Diagnostic Science, San Diego
Posted on 2018-09-11 in Clinical Pathology & Internal Medicine

For most species, laboratory hematologic evaluation (i.e., the hemogram) consists of an automated complete blood count (CBC), spun microhematocrit, and microscopic examination of a blood smear. Microscopic examination of a blood smear is an essential part of the hemogram as it can provide vital diagnostic information that is not provided by automated hematology analyzers. The morphology, distribution, and quantity of all three cell lines (RBCs, white blood cells (WBCs), and platelets) should be evaluated. RBC morphology is the focus of this session.

RBC morphology terms

* indicates infrequently observed cell or infrequently used term

A survey done by Newman et al.¹ examined agreement between clinical pathologists and clinicians regarding RBC morphology terms and their clinical value. The results pointed to important shortcomings in how these two groups communicate caused by discordant understanding of certain RBC morphology terms and, possibly, suboptimal reporting practices. Most of the RBC morphologic terms used by clinical pathologists are presented in Table 1. Images of the changes and comprehensive explanations of their clinical significance are available in various hematology texts^2,3 and many of them will be explored in this session. As a note, the term poikilocyte refers to any abnormally shaped RBC. Poikilocytes refer to RBCs with specific morphologies (e.g., acanthocytes, spherocytes) as well as abnormally shaped RBCs that do not fit into a specific category.

RBC morphology reporting

Consistent reporting of blood smear findings is important for laboratory-clinician communication and monitoring of disease over time. Findings should be expressed as clearly and objectively as possible. Most laboratories use a classification scheme to standardize blood smear findings. At Ethos Labs, the following semiquantitative reporting scheme is used:

Relevant RBC morphologies

Although some morphologic changes are of limited clinical utility, some provide important diagnostic information. Frequently used and/or clinically significant RBC morphologies are presented in Table 2.

Selected profiles of morphologic changes and their clinical significance are presented here:

• Polychromasia, anisocytosis, rubricytosis, Howell-Jolly bodies, stomatocytes, basophilic stippling: Often seen in animals with regenerative anemia. However, species differences exist (e.g., basophilic stippling is frequently seen in ruminants, but not small animals; horses typically do not have circulating evidence of regeneration; stomatocytes are most frequently seen in dogs).
• Schizocytes, acanthocytes: Associated with erythrocyte fragmentation (mechanical damage) secondary to microangiopathy, as may be seen secondary to neoplasia (in particular, hemangiosarcoma), disseminated intravascular coagulopathy, glomerulonephritis, and vasculitis. Acanthocytes may also be seen in dogs with liver disease or lipid metabolopathy.
• Spherocytes, agglutination: May be seen in animals with immune-mediated hemolytic anemia (IMHA).
• Heinz bodies, eccentrocytes: Evidence of oxidative damage to RBCs.
• Hypochromasia with associated poikilocytosis (including microcytes, schizocytes, keratocytes, acanthocytes, codocytes): Often seen in animals with iron deficiency.
• Ghost cells: If not lipemic “smudge” cells (seen in lipemic samples, resembling and sometimes described as ghost cells), an indicator of intravascular hemolysis (sometimes seen in IMHA or Heinz body hemolytic anemia).
• Ovalocytosis with macrocytosis: In dogs with persistent, nonregenerative anemia, a strong indicator of myelofibrosis.⁴
• Reticulocytosis in the absence of anemia: Although traditionally thought to indicate recovery from anemia or nonanemic chronic hypoxia (e.g., cardiovascular disease, pulmonary disease), the prevalence of reticulocytosis in the absence of anemia appears to be increasing in dogs.⁵ Several risk factors (or their cumulative effects) may be involved, including osteoarthritis and their various associated treatments, e.g., anti-inflammatories, nutraceuticals.
• Inappropriate rubricytosis (increased nucleated RBCs in the absence of a regenerative anemia): Lower numbers of nRBCs seen in splenectomized patients or following splenic contraction (adrenergic stress/excitement); Higher numbers may be seen with heat stroke, septicemia, and lead poisoning. May also be an indicator of dyserythropoiesis.
• Basophilic stippling and rubricytosis in the absence of regenerative anemia: Seen in lead poisoning in some species.

Conclusion

Microscopic examination of a blood smear is a crucial part of the hemogram. Recognizing individual RBC morphologic abnormalities and patterns of abnormalities may facilitate the diagnostic process. Furthermore, healthy communication between clinicians and laboratory personnel is important, as understanding the what, when, and why of reporting RBC abnormalities will lead to a more complete understanding of the hematologic state of the patient.

References

1. Newman AW, et al. Vet Clin Pathol 2014;43(4):487.
2. Harvey JW. Veterinary Hematology: A Diagnostic Guide and Color Atlas. 2012; Saunders.
3. Stockham SL, et al. Fundamentals of Veterinary Clinical Pathology. 2008; Blackwell Publishing.
4. Hollinger CH, et al. Vet Clin Pathol 2011;40(4);595.
5. Pattullo KM, et al. Vet Clin Pathol 2015; 44(1):26.

Photo credit: Modified and used with permission. By Coinmac – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=20155466