From the Guidelines
A normal Complete Blood Count (CBC) with abnormal blood cell morphology is a significant finding that requires further investigation, as it may indicate underlying conditions such as hemoglobinopathies, liver disease, infections, nutritional deficiencies, or early hematologic malignancies, despite normal numerical values. This is because the morphology of blood cells can provide important clues about the underlying health of the patient, even when the quantities of blood cells are within normal ranges. According to the guidelines outlined in 1, a peripheral blood smear review by a pathologist is essential to characterize the specific morphological abnormalities.
The next steps in evaluation may include additional testing, such as:
- Hemoglobin electrophoresis for red cell defects
- Flow cytometry for white cell abnormalities
- Bone marrow examination to evaluate the degree of hematopoietic cell maturation abnormalities and relative proportions, percentage of marrow blasts, marrow cellularity, presence or absence of ringed sideroblasts, and fibrosis, as recommended in 1 and 1
- Other useful screening laboratory studies, including serum erythropoietin, vitamin B12, red blood cell folate levels, and serum ferritin, as suggested in 1 and 1
Common morphological abnormalities that may be encountered include:
- Red cell variations, such as spherocytes, target cells, or schistocytes
- White cell changes, such as toxic granulation or Döhle bodies
- Platelet abnormalities
These morphological changes can be indicative of a range of underlying conditions, and regular follow-up CBCs may be warranted to monitor for progression, especially if the patient has symptoms or risk factors for hematologic disorders. As noted in 1, determining the presence of specific genetic abnormalities, such as PDGFRb gene rearrangements, may also be helpful in certain cases. Overall, a normal CBC with abnormal morphology is a finding that should not be ignored, and further evaluation is necessary to determine the underlying cause and to guide management.
From the Research
Significance of Normal CBC with Abnormal Blood Cell Morphology
- A normal Complete Blood Count (CBC) with abnormal blood cell morphology can be significant in identifying potential hematolymphoid neoplasms, as laboratory professionals can identify CBC and peripheral blood smear findings that raise this possibility 2.
- Abnormal blood cell morphology can be associated with various conditions, including anemia, thrombocytopenia, leukopenia, polycythemia, thrombocytosis, and leukocytosis, and a structured approach is necessary to interpret and pursue abnormal CBC results 3.
- Red blood cell morphologic abnormalities can occur in patients with COVID-19, and a systematic evaluation of RBC morphology at peripheral blood smear can provide valuable information on the clinical significance of these abnormalities 4.
- Automated nucleated RBC measurement can detect low-level nucleated RBCs in patients with otherwise normal CBC parameters, which may be present in individuals without increased erythropoiesis or a pathologic bone marrow process 5.
- Morphologic changes in white blood cells, including neutrophilia and lymphopenia, can be associated with the severity of COVID-19 infection, and abnormal WBC morphology can be predictive of disease progression 6.
Clinical Implications
- A normal CBC with abnormal blood cell morphology requires further evaluation, including peripheral blood smear review and potentially flow cytometric immunophenotyping, to establish a definitive diagnosis 2.
- The integration of peripheral blood smear review findings with clinical and other information is crucial in recommending additional studies and recognizing situations where the results of peripheral blood smear review and flow cytometric immunophenotyping do not explain the clinical findings 2.
- Daily CBC with manual WBC differential can be useful in monitoring hospitalized patients with COVID-19 for numerical and morphologic changes predictive of poor outcome and signs of disease progression 6.