A 26-year-old male presents one month post splenectomy with acute blood loss anemia due to trauma and associated surgeries. Peripheral blood smear shows normocytic and hypochromic anemia. Red blood cells have a marked increase in vacuoles varying in size and quantity, but no other morphological abnormalities are present. The high quantity of vacuoles in the red blood cells is consistent with observations seen in post splenectomy individuals (Reinhart et al, 1988). Under normal circumstances red blood cells form small vacuoles often needing transmission electron microscopy to be seen. Although the mechanism is not fully understood, the spleen is presumed to take a vital role in removing these inclusions from red blood cells (Holroyde et al, 1970). In asplenia the small vacuoles remain allowing them to cluster and potentially fuse together to form larger vacuoles that are detectable under light microscopy. Interestingly, other common morphological features commonly seen in asplenia such as Howell jolly bodies, acanthocytes, spherocytes, and target cells are absent from this patient. The formation of vacuoles in the red blood cells can be attributed to other differential diagnosis including alcoholism (Yeung et al, 1988), myeloid neoplasms in relation to VEXAS (Gurnari et al, 2021), artefacts (Lynch, 1990), medication (Ben-Bassat et al, 1972) and infections (Bateman et al, 2017).  The patient’s unremarkable medical history makes alcoholism, myeloid neoplasms and VEXAS unlikely reasons for the increased number of vacuoles seen. Artefacts from smear preparation are also unlikely as the vacuoles have been present on all smears prepared post splenectomy. The patient was treated with ceftazidime and piperacillin-tazobactam for sepsis and polymicrobial peritonitis. Along with having vacuoles in his white cells, his infection and treatment may also be a cause for the increased number of circulating vacuoles in his red blood cells.  

References 

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Ben-Bassat, I., Bensch, K. G., & Schrier, S. L. (1972). Drug-induced erythrocyte membrane internalization. The Journal of clinical investigation, 51(7), 1833–1844. https://doi.org/10.1172/JCI106985  

Gurnari, C., Pagliuca, S., Durkin, L., Terkawi, L., Awada, H., Kongkiatkamon, S., Zawit, M., Hsi, E. D., Carraway, H. E., Rogers, H. J., Visconte, V., & Maciejewski, J. P. (2021). Vacuolization of hematopoietic precursors: an enigma with multiple etiologies. Blood, 137(26), 3685–3689. https://doi.org/10.1182/blood.2021010811  

Holroyde, C. P., & Gardner, F. H. (1970). Acquisition of autophagic vacuoles by human erythrocytes. Physiological role of the spleen. Blood, 36(5), 566–575.  

Lynch, E. C. (1990). Peripheral Blood Smear (H. K. Walker, W. D. Hall, & J. W. Hurst, Eds.). PubMed; Butterworths. https://www.ncbi.nlm.nih.gov/books/NBK263/  

Reinhart, W. H., & Chien, S. (1988). Red cell vacuoles: their size and distribution under normal conditionsand after splenectomy. American journal of hematology, 27(4), 265–271. https://doi.org/10.1002/ajh.2830270407  

Yeung, K. Y., Klug, P. P., & Lessin, L. S. (1988). Alcohol-induced vacuolization in bone marrow cells ultrastructure and mechanism of formation. Blood cells, 13(3), 487–502.