In this study, infection risk in non-splenectomized patients exhibiting HJBs was investigated, revealing that older age (≥ 65 years) and reduced splenic volume (< 34 mL) independently increased susceptibility to sepsis. Although a significantly smaller actual-to-ideal splenic volume ratio (≤ 82%) showed a trend toward sepsis risk, this difference was not statistically significant. These findings suggest that a spleen volume threshold of 34 mL may be clinically meaningful for identifying patients at higher risk of severe infections, particularly sepsis. Moreover, older age emerged as a robust predictor of infection. This highlights the potential value of targeted prophylactic measures—such as vaccinations and antibiotic therapy—in patients with suspected functional hyposplenism.

The precise mechanisms underlying splenic atrophy in functional hyposplenism remain poorly understood. Picardi et al.[14] hypothesized that immune-mediated processes similar to those causing pancreatic atrophy in diabetes may underlie progressive splenic shrinkage. Supporting this immunological perspective, the study shows that patients with autoimmune pancreatitis initially presented with splenomegaly, which later progressed to splenic atrophy after steroid treatment [15]. The proposed mechanism involves the expansion of autoreactive lymphocytes that deplete naive lymphocyte populations, ultimately reducing spleen volume. Similarly, experimental studies in murine models show that persistent antigen presentation can induce splenic atrophy [16]. Consistent with these observations, a case of prolonged chronic graft-versus-host disease (GVHD) is associated with ongoing splenic atrophy [5], further supporting an immune-mediated etiology. Although these findings strongly suggest an immunological basis, further research is warranted to elucidate the precise biological pathways involved.

HJBs are well-recognized markers of impaired splenic function under standard light microscopy [3,4,5,6]. Although HJBs’ sensitivity and specificity may be lower than those of more specialized tests—such as radioisotope scanning, flow cytometry for IgM+ CD27+ B cells, or pitted erythrocyte counts [6, 17,18,19,20]—their simplicity and low cost make them a practical screening method across diverse clinical settings. Patients with detectable HJBs could undergo additional confirmatory testing or closer clinical monitoring, especially if imaging also reveals reduced splenic volume. Integrating HJBs detection with imaging findings enhances the ability of clinicians to identify individuals at risk for functional hyposplenism.

CT–based measurement of the splenic volume provides greater precision than traditional single-dimensional assessments (e.g., measuring the splenic long axis) [12, 15]. Although splenomegaly is commonly reported in radiologic assessment, splenic atrophy is often overlooked or underreported [21]. Although indices such as the spleen index are used to evaluate splenomegaly, statistical reports on splenic atrophy remain limited, and no clear criteria have been established [22]. Whereas Picardi et al. [14] identified a two-dimensional splenic index using ultrasound, our CT-derived volumetric cut-off provides a three-dimensional, operator-independent assessment that can be applied to routine abdominal CT scans, thereby enhancing the clinical utility of imaging-based evaluation for functional hyposplenism. Nevertheless, reduced splenic volume alone does not definitively diagnose functional hyposplenism. Radioisotope-based assays and specialized immunological tests remain the gold standard for confirming true splenic dysfunction [23, 24]. However, these modalities are expensive, require specialized equipment, and may not be readily available in all healthcare settings. Consequently, CT-based spleen volume measurements serve as an accessible and relatively accurate indicator of potential functional hyposplenism—especially when interpreted alongside HJB status [5, 6].

The spleen plays a multifaceted role in immune defense, contributing to antigen presentation, antibody production, phagocytosis, and opsonization of blood-borne pathogens [1]. A previous study [25] shows that functional hyposplenism increases the risk of infection, particularly sepsis. However, quantifying this risk relative to that of splenectomized patients remains challenging, given limited comparative data [26]. In splenectomized individuals, the risk of overwhelming post-splenectomy infection (OPSI) is > 50 times that of the general population, with S. pneumoniae as the predominant causative pathogen (50–90% of cases), followed by H. influenzae type b and N. meningitidis [27]. Functional hyposplenism may confer similar susceptibility; however, direct comparative evidence is lacking [26]. The microorganisms most commonly responsible for OPSI include Streptococcus pneumoniae, Haemophilus influenzae type b, and N. meningitidis, with less frequently reports on Klebsiella pneumoniae and Salmonella typhi, among others [7]. Therefore, a similar distribution of pathogens was expected in our cohort of patients with functional hyposplenism. However, Klebsiella pneumoniae emerged as the most frequently detected organism. This unexpected predominance may reflect the widespread use of effective vaccines against Streptococcus pneumoniae, Haemophilus influenzae type b, and N. meningitides, but no commercially available vaccine currently exists for Klebsiella pneumoniae.

Given this vulnerability, clinical guidelines have increasingly shifted to treating patients with functional hyposplenism similar to those who have undergone splenectomy. In particular, the latest British guidelines17, which reference our single-center research on HJBs detection [6], emphasize that both splenectomized and functionally hyposplenic patients require vaccination against S. pneumoniae, H. influenzae type b, and N. meningitidis. Moreover, lifelong prophylactic antibiotics therapy is recommended for individuals at high risk of pneumococcal infection—especially young children (< 16 years), older adults (> 50 years), patients with poor serological responses, or those with a history of invasive pneumococcal disease. Other high-risk populations include patients with hematological malignancies—particularly those undergoing splenic irradiation, experiencing GVHD, or long-term immunosuppression—as well as those in the early postoperative period following post-splenectomy (within 1–3 years). These recommendations highlight the significance of accurately identifying patients with potential splenic dysfunction, whether anatomical or functional.

Our findings support this approach. Through the establishment of a specific spleen volume threshold (< 34 mL) associated with increased sepsis risk and identifying older age as an additional key predictor, we contribute further details to the existing evidence base. These findings may help clinicians in personalizing preventive strategies, including timely vaccination and antibiotic prophylaxis. Nonetheless, larger prospective studies are warranted to determine the optimal frequency and methodology for monitoring splenic volume. They are also needed to refine prophylactic approaches (e.g., duration of antibiotic use) and to directly compare outcomes between patients with functional hyposplenism and those who have undergone splenectomy.

Despite these findings, this study has some limitations. First, the single-center, retrospective design may limit generalizability, and reliance on culture-positive cases may underestimate the incidence of infection. Second, incomplete data on vaccination status and antibiotic prophylaxis hindered a thorough evaluation of their protective effects. Third, since many patients underwent CT imaging after an infectious event, time-dependent sepsis risks could not be calculated. Finally, although HJB detection is a practical screening tool for splenic dysfunction, its diagnostic accuracy is inferior to that of more specialized methods. Larger prospective studies—particularly those incorporating etiologically stratified cohorts—are required to determine whether specific patient subgroups exhibit distinct infection profiles or require more intensive prophylaxis. A lack of microbiological data meant that subgroup analyses of causative organisms by age or spleen volume could not be conducted in this study. Future studies with larger sample sizes are needed to explore whether specific pathogens are more prevalent in specific subgroups of patients. While CT-based spleen volumetric measurement provides precise splenic function assessment, repeated imaging poses cost and resource challenges. Therefore, further research into alternative or targeted screening protocols may help balance the feasibility and clinical benefits.

Older age (≥ 65 years) and reduced splenic volume (< 34 mL) independently predict sepsis risk in non-splenectomized patients with HJBs. These findings underscore the need to carefully evaluate splenic volume alongside HJBs detection to identify and manage functional hyposplenism. Future prospective investigations should aim to refine prophylactic strategies, establish optimal screening intervals, deepen understanding of the underlying mechanisms, and ultimately improve outcomes in this at-risk population.