Volume 31, Issue 9, September 2025, 102787Author links open overlay panel, , , , , AbstractBackground

The clinical significance of leukocyte destruction morphology in routine peripheral blood smears remains underexplored. This study aimed to systematically quantify leukocyte destruction and correlate these findings with clinical course, etiology, and outcome in patients with suspected sepsis.

Methods

This was a retrospective observational study involving 30 intensive care unit (ICU) patients with suspected sepsis. Peripheral blood smear findings were evaluated chronologically, with the day of blood culture collection designated as Day 0, followed by four distinct phases. Leukocyte destruction was defined as clear evidence of cytoplasmic or nuclear dissolution. Correlations were assessed with 28-day prognosis and symptom onset (acute [no preceding symptoms before admission] vs. non-acute [preceding symptoms present]).

Results

Leukocyte destruction showed no significant difference concerning 28-day mortality. However, it was significantly more frequent in acute onset cases within the first 48 h (7.0 % vs. 3.7 %, p < 0.05). Conversely, cases with toxic granulation were significantly more common in non-acute onset cases within the first 48 h (70 % vs. 14 %, p < 0.01).

Discussion

The patterns of leukocyte destruction and toxic granulation may provide insights into the underlying pathophysiology of critically ill patients and warrant further investigation.

Graphical abstractDownload: Download high-res image (243KB)Download: Download full-size imageIntroduction

Morphological destruction of leukocytes, visible as cytoplasmic or nuclear disintegration in peripheral blood smears, is sometimes encountered; however, it is rarely quantified or systematically studied in clinical hematology. While such changes may reflect mechanical artifact, increasing evidence suggests that they are associated with underlying pathophysiological processes, especially in the context of severe infection or acute stress. Despite the routine use of blood smears in clinical practice, the diagnostic and prognostic value of leukocyte destruction morphology remains unclear.

Recent advances in neutrophil biology have revealed that neutrophil extracellular traps (NETs)—web-like structures composed of chromatin and antimicrobial proteins—play a critical role in host defense and immunopathology [1]. NETs formation can be triggered by both infectious and sterile inflammatory stimuli, and their excessive production has been linked to thrombosis [2], and organ dysfunction in sepsis [3,4], COVID-19 [4,5], and other acute illnesses [6]. However, most studies have relied on molecular or imaging approaches, and few have addressed whether NETs-like morphology or other forms of leukocyte destruction can be reliably detected and quantified in routine blood smears.

To date, there have been no original studies systematically quantifying leukocyte destruction morphology in the peripheral blood of patients with suspected sepsis and comparing these findings to other acute clinical presentations. The present study addresses this gap by providing a detailed morphological and temporal analysis of leukocyte destruction in critically ill patients, evaluating its association with clinical course and outcome, and discussing its relationship to emerging concepts in neutrophil biology.

Section snippetsPatient selection and clinical data

This retrospective observational study was conducted at Nagasaki University Hospital and included patients admitted to the intensive care unit (ICU) between November 2014 and May 2015. The study was approved by the ethics committee of Nagasaki University Hospital (approval number, 14102792).

Eligible patients were those who underwent blood culture testing due to suspected sepsis during their ICU stay. Written informed consent was obtained from all participants or their legal surrogates prior to

Leukocyte destruction and clinical associations

For clinical correlation, the mean proportion of leukocyte destruction in Phase 1 (Day 0–2) was analyzed in relation to various clinical variables.

For prognostic associations, no statistically significant difference in leukocyte destruction was found between survivors and non-survivors (p = 0.56, Fig. 2A). The mean proportion of leukocyte destruction in Phase 1 was 4.3 ± 0.8 % (n = 22, mean ± standard error of the mean) in survivors and 5.0 ± 1.3 % (n = 8) in non-survivors.

For onsets, patients

Discussion

The present study is likely the first to systematically quantify leukocyte destruction morphology in the peripheral blood of patients with suspected sepsis and acute systemic illness, and to correlate these findings with clinical course and outcome. While prior research has established the importance of NETs and neutrophil activation in the pathogenesis [1,[6], [7], [8]], no studies were found that explored the practical utility of routine blood smear analysis for detecting these phenomena.

Conclusion

The patterns of leukocyte destruction and toxic granulation may provide insights into the underlying pathophysiology of critically ill patients and warrant further investigation.

Author contributions

Al authors meet the above ICMJE authorship criteria.

YM contributed to conceptualization, investigation, and data curation. YM was also responsible for the original draft writing, visualization, and project administration, as well as the organization and coordination of the trial. MS contributed to collecting resources. KT and HH contributed to methodology and validation. TH and KY provided supervision. All authors contributed to the review and editing of the final manuscript.

Declaration of generative AI and AI-assisted technologies in the writing process

During the preparation of this work, the authors used Perplexity (Perplexity AI) and Gemini (Google AI) in order to assist with sentence structuring and rephrasing for improved flow. After using these tools/services, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Funding

This research was supported by a Grant-in-Aid for Challenging Exploratory Research (grant number 15K15381 to YM).

Conflict of interest

The authors declare no conflicts of interest related to this study.

Acknowledgement

We extend our sincere thanks to Haruka Obayashi, Minami Okamoto, and Yukimi Katagami for their invaluable assistance with sample preparation.

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