Sepsis, a life-threatening organ dysfunction resulting from a dysregulated host response to infection, remains a leading cause of morbidity and mortality in intensive care units worldwide (1–3). Its most severe clinical manifestation, septic shock, is characterized by profound circulatory and cellular/metabolic dysfunction and is associated with alarmingly high mortality (4, 5). The pathophysiological complexity of sepsis involves a dysregulated interplay among widespread inflammation, immune suppression, and coagulation dysfunction, thereby rendering early and accurate assessment of disease severity and prognosis critically important for guiding therapeutic decisions.

The current diagnostic paradigm for sepsis relies primarily on clinical criteria and microbiological cultures. Although microbiological culture remains the gold standard for pathogen identification, its utility in guiding urgent clinical decision-making is limited by several inherent drawbacks, including prolonged turnaround times (typically 24–72 h) and suboptimal sensitivity (6, 7). This diagnostic and prognostic gap underscores the need for reliable and rapidly available biomarkers to complement clinical judgment. Although numerous biomarkers have been investigated, no single biomarker adequately captures the multifaceted nature of sepsis. Consequently, a panel of biomarkers reflecting distinct pathological axes may offer superior clinical utility (8).

This study focuses on the combined analysis of procalcitonin (PCT), D-dimer (D-D), and lactate dehydrogenase (LDH), leveraging their distinct yet complementary pathophysiological roles in sepsis. PCT is a well-established biomarker of systemic bacterial infection and the associated inflammatory response, and its kinetic profile is useful for both diagnosis and monitoring therapeutic efficacy (9). D-D, a marker of activated coagulation and fibrinolysis, reflects the severity of sepsis-associated coagulopathy, a major contributor to organ dysfunction and mortality (10). LDH, which is released following cellular injury, serves as a non-specific marker of tissue hypoxia and cellular damage, providing an indicator of downstream effects of shock and microcirculatory dysfunction in sepsis (11).

While each biomarker provides clinically relevant information when considered individually, their combined application addresses three core pathophysiological components of sepsis: inflammation (PCT), coagulopathy (D-D), and cellular injury (LDH). We hypothesize that this biomarker panel will enable a more comprehensive assessment than any single biomarker alone. Specifically, we propose two hypotheses: (1) elevated levels of all three biomarkers on admission will more accurately identify patients at high risk of progression to septic shock, and (2) dynamic changes in these biomarkers during hospitalization will provide improved prognostic stratification of clinical outcomes. Accordingly, this study aims to investigate the independent and combined associations of PCT, D-D, and LDH levels with sepsis severity and clinical outcomes, with the goal of evaluating a pragmatic multi-marker panel to support clinical assessment.

Sepsis remains a major global health challenge and is associated with substantial morbidity and mortality. Timely and accurate assessment is critical, as progression to septic shock markedly increases the risk of multiple organ dysfunction and death (13–15). However, the early clinical manifestations of sepsis are often non-specific, and definitive microbiological diagnosis via culture is invariably delayed, thereby creating a therapeutic window during which rapid clinical assessment and severity stratification are pivotal for disease diagnosis and management (16, 17). This limitation underscores the need for objective and readily available biomarkers to complement clinical judgment. Accordingly, this study aimed to identify laboratory-based factors associated with septic shock and to evaluate their utility in assessing disease severity and prognosis in patients with sepsis.

This study demonstrates that levels of PCT, D-D, and LDH, either individually or in combination, are significantly associated with disease severity and clinical outcomes in patients with sepsis. The key findings are twofold: first, elevated levels of PCT, D-D, and LDH on admission were independently associated with the development of septic shock; second, serial monitoring of these biomarkers revealed distinct dynamic patterns that were strongly correlate with final clinical outcomes.

These results corroborate and extend the existing literature on individual biomarkers. The role of PCT as an indicator of systemic bacterial infection and inflammatory burden is well established (18, 19). This study reinforces this role by quantifying the association between PCT levels and disease severity, thereby its utility not only as a diagnostic marker but also as an indicator of the magnitude of the host’s dysregulated inflammatory response. Similarly, elevation of D-D is a recognized hallmark of sepsis-associated coagulopathy, a key contributor to microvascular thrombosis and end-organ damage (20, 21). The present analysis strengthens this association by demonstrating that elevated D-D levels are independently associated with the development of septic shock. Notably, D-D levels exhibited a divergent temporal trajectory, increasing significantly in patients with poor outcomes. This dynamic behavior suggests that D-D may serve as a sensitive indicator of ongoing, potentially treatment-resistant coagulopathy, providing prognostic information beyond a single baseline measurement.

Although LDH is a relatively non-specific marker of cellular injury, its pronounced elevation in patients with septic shock is consistent with the pathophysiology of global tissue hypoxia and cellular necrosis (23–25). The absence of a significant decline in LDH levels among patients with poor outcomes further underscores its value as a persistent indicator of cellular damage, complementing the inflammatory and coagulation profiles reflected by PCT and D-D. The elevation of aspartate aminotransferase (AST) observed in the septic shock group likely reflects concomitant hepatic or cardiac injury (22). However, the contribution of AST to sepsis pathophysiology appears less direct than that of the primary biomarker triad, which collectively reflects the core perturbations of inflammation (PCT), coagulation (D-D), and cellular injury (LDH).

The principle clinical strength of this study lies in the evaluation of the combined and dynamic use of these biomarkers. Individually, each biomarker provides insight into a specific aspect of sepsis pathophysiology; collectively, they enable a more comprehensive assessment of patient status. The consistent decline of all three biomarkers in patients with favorable outcomes, compared with their persistent elevation or increase in patients with poor outcomes, reflects differential responses to therapy. These findings support a shift from static, admission-only biomarker assessment toward a dynamic monitoring strategy, in which longitudinal trends may provide earlier and more reliable prognostic information than absolute values obtained at a single time point.

Several limitations should be considered when interpreting the findings of this study. First, as a single-center, retrospective study, the results may be influenced by inherent selection bias. The included patients represent a specific local population and healthcare environment, which may limit the generalizability of the findings to other institutions or regions with differing patient demographics, clinical practices, or resource availability.

Second, the study period spanned from 2020 to 2025, during which clinical protocols, including those for sepsis management and biomarker testing, may have evolved. Third, the classification of patient outcomes, particularly discharge status (e.g., “improved” vs. “poor prognosis”), may be subject to variability in clinical decision-making. Discharge timing and criteria may vary among treating physicians, potentially introducing misclassification bias.

Fourth, a primary limitation of this study lies in its retrospective design, which precluded the ability to obtain and adjust for several known and clinically important prognostic confounders (e.g., age, severity of underlying illness, such as the SOFA score, and specific ICU interventions). Consequently, the associations observed between the biomarkers (PCT, D-D, and LDH) and clinical outcomes may be subject to residual confounding. These findings should therefore be interpreted as preliminary signals of association rather than as evidence establishing these biomarkers as independent predictive factors. Future multicenter prospective studies with standardized protocols are needed to validate these findings and to enhance their external validity.

In conclusion, this study demonstrates that levels of PCT, D-D, and LDH are significantly associated with disease severity and clinical outcomes, highlighting their potential utility in the early assessment of patients with sepsis. More importantly, serial measurements of this biomarker triad reveal dynamic patterns that are strongly associated with clinical outcomes, providing a practical tool for monitoring treatment response. Incorporating this readily available biomarker panel into routine clinical practice may facilitate earlier identification of high-risk patients, guide the intensity of therapeutic interventions, and improve the personalization of sepsis management.