CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Editor: Frederick L. Kiechle, MD, PhD
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Absolute neutrophil count—exclude immature granulocytes
Pediatric reference ranges for chem panels for intraosseous and venous specimens
Speech recognition—why varying user experiences with the same product?
Q. We have always considered the absolute neutrophil count to include segmented neutrophils and bands only. Should other immature cells such as myelocytes, promyelocytes, and metamyelocytes be included in this calculation?
A. The absolute neutrophil count (ANC) is a critically important component of the complete blood count. The reference interval in adults is typically 1.5 to 8.0 × 109/L (1,500 to 8,000 cells/µL). Absolute neutrophilia is usually an indicator of systemic infection or inflammatory response. Neutropenia, on the other hand, strongly correlates with increased susceptibility to infection. The ANC should include segmented neutrophils and band neutrophils only. The rationale for excluding immature granulocytes (promyelocytes, myelocytes, and metamyelocytes) is that they lack the immunological function of band and segmented neutrophils in the clinical setting of infection. Mature neutrophils and bands possess the necessary cellular machinery to combat infectious microorganisms and clear unwanted cellular debris through mechanisms such as extravasation into tissue, degranulation, and phagocytosis.1 The ANC can therefore be regarded as a functional measure with vital clinical utility.
Although not incorporated into the ANC, immature granulocytes should be recognized and included in the white blood cell differential. Identifying these cells in the peripheral blood may provide important diagnostic information, particularly in the setting of myeloid neoplasms. Blasts, when present, should be reported separately since their numbers are important for classifying acute leukemias, myelodysplastic syndromes, and myeloproliferative neoplasms. Historically, automated white blood cell differential counts performed by hematology analyzers were limited in terms of evaluating granulocytes, with the neutrophil category often including not only segmented neutrophils and bands but also at least a subset of immature granulocytes. Manual differential counts consisting of several hundred cells were typically required to accurately classify immature granulocytes, although this method may lack clinical relevance if a small proportion of immature granulocytes is present. Recent advances have improved the automated detection of immature granulocytes. Some modern automated hematology analyzers use a flow-cytometry–based approach to detect and quantitate immature granulocytes alongside the standard five-part differential. Recent studies evaluating this methodology have found that the instrumentation is quite accurate in classifying immature granulocytes up to a threshold of 10 percent of the total leukocytes.2 However, identification of immature granulocytes by automated cell identification methods appears to lack sensitivity in screening for infection.3 The ANC remains the most clinically important parameter in this regard.
- Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia: Saunders/Elsevier; 2010.
- Bourne S, Ma N, Gulati G, Florea AD, Gong J. Evaluation of automated versus manual immature granulocyte counts. Lab Medicine. 2013;44:282–287.
- Ansari-Lari MA, Kickler TS, Borowitz MJ. Immature granulocyte measurement using the Sysmex XE-2100. Relationship to infection and sepsis. Am J Clin Pathol. 2003;120:795–799.
Parker W. Clement, MD, Hematopathology Fellow, University of Utah School of Medicine, Salt Lake City, Junior Member, CAP Hematology/Clinical Microscopy Resource Committee
Jay L. Patel, MD, Assistant Professor of Pathology, University of Utah School of Medicine, Salt Lake City, Medical Director, Hematopathology Laboratory, ARUP Laboratories, Salt Lake City, Member, CAP Hematology/Clinical Microscopy Resource Committee
Q. Are pediatric reference ranges for chemistry panels from tibial marrow the same as for peripheral blood? If not, what are they?
A. There is not enough information available in the literature to answer that question. Matrix effects from marrow tissue and bone particulates as well as equilibrium issues with systemic circulation are potential sources of interference with this type of specimen. There are only a small number of studies that compare intraosseous to venous specimen laboratory results. All of the studies are small but do show a correlation for red cell, hemoglobin, and hematocrit results. However, some studies have shown that the correlation between intraosseous and venous samples for common laboratory measures is dependent on the volume of marrow waste drawn. Additionally, we could not identify any manufacturers that have validated their respective instruments for intraosseous specimen types. Consequently, any testing of intraosseous blood would be considered a laboratory-developed test, thus requiring validation studies and development of reference interval ranges for the institution.
We recommend discussing this issue with your local pediatric emergency medicine physicians to assess how many of these specimens they might be sending under the guise of venous collected specimens and cautioning them that testing on such specimens has the potential to be erroneous due to matrix effects and systemic/intraosseous equilibrium issues.