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Updated: Aug 17, 2026

Prediction of Red Blood Cell Antibody Significance Using the Monocyte-Macrophage Assay
Published on: February 7, 2025
Macrocytosis associated with monoclonal gammopathy
Andrew L Horstman1, Stephanie L Serck, Ronald S Go
1Section of Hematology, Gundersen Lutheran Medical Center, La Crosse, WI 54601, USA.
Objective:
To report the potential association between unexplained macrocytosis and monoclonal gammopathy.
Methods:
We retrospectively reviewed the medical records of patients who had monoclonal protein detected by serum electrophoresis and immunofixation from October 1999 until September 2003 at our institution. Patients with concomitant macrocytosis were included in this study. We collected data on patient demographics, evaluations performed for macrocytosis, pertinent laboratory tests relevant to the diagnosis of monoclonal gammopathy and presence of associated hematologic disorders.
Results:
We identified 258 patients with monoclonal gammopathy. Thirty-one (12%) of them had concomitant macrocytosis. Of the latter group, 14 (5%) patients had no identifiable cause of macrocytosis after thorough evaluation and were considered to have macrocytosis associated with monoclonal gammopathy. The median values for mean cell volume and serum monoclonal protein were 103.9 fL (range 100.8-109.8) and 1.95 gm/dL (range 0.8-4.3), respectively. Most patients had IgG (71%) and kappa light chain (79%). All of the 11 (of 14) patients who underwent a bone marrow biopsy as part of the initial evaluation had megaloblastoid maturation of the erythroid precursors. No correlation was found between the level of serum monoclonal protein and the degree of macrocytosis (r = +0.48, P = 0.08). After a median follow-up of 22.5 month (range 3-60+), all but one patient had persistent but stable macrocytosis.
Conclusion:
Macrocytosis can be a manifestation of monoclonal gammopathy. Disorders associated with monoclonal gammopathy should be considered in the differential diagnoses during evaluation of macrocytosis.
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