Sepsis is a life-threatening syndrome resulting from a dysregulated host response to infection, leading to acute organ dysfunction and, if not recognized and treated promptly, progression to septic shock and death. Although significant advances in antimicrobial therapy, critical care management, and implementation of the Surviving Sepsis Campaign guidelines have contributed to improved patient outcomes, sepsis continues to be a major cause of morbidity and mortality worldwide. Over the past decade, mortality associated with sepsis has declined from approximately 37% to around 30%; however, it remains unacceptably high. Simultaneously, the incidence of sepsis has increased substantially among hospitalized patients and is increasingly being recognized in emergency and outpatient settings. Therefore, early identification of patients at risk of severe disease is essential to facilitate timely therapeutic interventions and improve clinical outcomes.[1,2] Early diagnosis of sepsis remains challenging because its clinical manifestations often overlap with those of other inflammatory and infectious conditions. Consequently, considerable research has focused on identifying laboratory biomarkers that can aid in the early diagnosis, assessment of disease severity, and prediction of prognosis. Despite the evaluation of numerous biomarkers, no single laboratory parameter has demonstrated sufficient sensitivity and specificity to accurately diagnose or predict the severity of sepsis in all patients. As a result, current research emphasizes the combined use of multiple clinical, hematological, and biochemical markers to improve diagnostic accuracy and facilitate early risk stratification.[3] Routine hematological and biochemical investigations are inexpensive, widely available, and rapidly obtainable, making them valuable tools in the management of patients with suspected sepsis. A complete blood count (CBC), one of the most commonly performed laboratory investigations, provides several hematological indices that reflect the host inflammatory response. Sepsis is frequently associated with leukocytosis or leukopenia, neutrophilia, lymphocytopenia, eosinopenia, thrombocytopenia, and alterations in platelet indices, all of which have been linked to disease severity and clinical outcomes. Similarly, biochemical markers such as C-reactive protein (CRP), procalcitonin (PCT), serum ferritin, lactate dehydrogenase (LDH), D-dimer, liver enzymes (ALT and AST), coagulation parameters including prothrombin time (PT) and activated partial thromboplastin time (APTT), serum bilirubin, renal function tests, and serum lactate provide important information regarding systemic inflammation, tissue injury, organ dysfunction, and prognosis.[4–7] Several studies have demonstrated that abnormalities in these hematological and biochemical markers correlate with increasing severity of sepsis, development of organ dysfunction, prolonged hospital stay, and mortality. Since no individual biomarker is sufficiently reliable when used alone, a combination of routinely available laboratory parameters may provide a practical and cost-effective approach for early identification of high-risk patients, particularly in resource-limited healthcare settings. Furthermore, understanding the relationship between these laboratory markers, underlying comorbidities, and disease progression may assist clinicians in risk stratification, guiding therapeutic decisions, and predicting patient outcomes.[8] Therefore, the present study was undertaken to evaluate the role of routine hematological and biochemical markers in predicting the severity of sepsis and to determine their usefulness as readily available prognostic indicators in patients presenting with sepsis.

Study Design and Setting The present prospective observational study was conducted in the Department of Pathology, Shri Balaji Institute of Medical Science, Raipur, Chhattisgarh, under the supervision of the Associate Professor, Department of Pathology. The study included patients presenting with clinical features suggestive of sepsis who fulfilled the predefined inclusion and exclusion criteria. The study was carried out after obtaining approval from the Institutional Ethics Committee, and written informed consent was obtained from all participants or their legally authorized representatives prior to enrolment. Consecutive eligible patients admitted to the hospital during the study period were included in the study. Study Population A total of 80 consecutive patients with suspected sepsis were enrolled using a consecutive sampling technique during the study period. Inclusion Criteria Patients aged 18 years and above with suspected or confirmed infection who fulfilled the diagnostic criteria for sepsis were included in the study. Sepsis was defined as the presence of a documented or clinically suspected infection together with two or more systemic inflammatory response syndrome (SIRS) criteria, including: • Body temperature >38°C or <36°C • Heart rate >90 beats/minute • Respiratory rate >20 breaths/minute or PaCO₂ <32 mmHg • Total leukocyte count >12,000/mm³ or <4,000/mm³, or >10% immature (band) forms Patients with severe sepsis were identified by the presence of sepsis associated with organ dysfunction, tissue hypoperfusion, or hypotension. Organ dysfunction was defined by one or more of the following: systolic blood pressure ≤90 mmHg or mean arterial pressure ≤75 mmHg despite adequate fluid resuscitation, arterial hypoxemia (PaO₂ ≤75 mmHg without pre-existing pulmonary disease), metabolic acidosis (pH ≤7.30 or base deficit ≥5 mEq/L), oliguria (urine output ≤30 mL/hour for at least 2 hours despite adequate fluid replacement), acute alteration in mental status, or disseminated intravascular coagulation (INR >1.2 times normal with D-dimer ≥500 ng/mL or platelet count ≤100,000/mm³). Septic shock was defined as persistent hypotension requiring vasopressor support despite adequate fluid resuscitation. Neurological status was assessed using the Glasgow Coma Scale (GCS), and disease severity was evaluated using the Simplified Acute Physiology Score II (SAPS II). Exclusion Criteria • Patients with any of the following conditions were excluded: • Chronic liver disease or cirrhosis • Chronic kidney disease • Diabetes mellitus • Chronic obstructive pulmonary disease (COPD) • Malignancy • Autoimmune disorders • Patients receiving corticosteroids, chemotherapy, or other immunosuppressive therapy • Hospital-acquired infections • Patients with poor baseline functional status or those unwilling to participate in the study Data Collection A detailed clinical history and physical examination were performed for all enrolled patients. Blood cultures and cultures from other suspected sites of infection were obtained before initiation of antimicrobial therapy whenever feasible. Additional investigations, including chest radiography, ultrasonography, computed tomography (CT), or other imaging modalities, were performed as clinically indicated to identify the source of infection. Venous blood samples were collected under aseptic precautions at the time of admission. Hematological parameters were analyzed using an automated hematology analyzer and included: • Total white blood cell (WBC) count • Red blood cell (RBC) count • Platelet count • Absolute neutrophil count (ANC) • Immature granulocyte (IG) count Biochemical investigations included: • Serum procalcitonin (PCT) • C-reactive protein (CRP) These hematological and biochemical markers were evaluated for their association with the severity of sepsis. Patient Management All patients received empirical broad-spectrum antimicrobial therapy according to institutional sepsis management protocols. Antibiotic therapy was subsequently modified based on microbiological culture and antimicrobial susceptibility reports whenever indicated. Patients requiring advanced organ support or intensive monitoring were transferred to the intensive care unit (ICU) as per clinical judgment. Statistical Analysis Data were entered into Microsoft Excel and analyzed using IBM SPSS Statistics version 25.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median (IQR), while categorical variables were presented as frequencies and percentages. Comparisons between groups were performed using the Independent Student's t-test or Mann–Whitney U test for continuous variables and the Chi-square test or Fisher's exact test for categorical variables, as appropriate. Receiver Operating Characteristic (ROC) curve analysis was used to assess the predictive performance of hematological and biochemical markers for sepsis severity. A p-value <0.05 was considered statistically significant.

Table 1. Age-wise distribution of study participants (n = 80) Age Group (years) Number (n) Percentage (%) 18–30 12 15.0 31–45 20 25.0 46–60 28 35.0 >60 20 25.0 Total 80 100.0 The majority of the study participants belonged to the 46–60 years age group (35.0%), followed by the 31–45 years and >60 years age groups (25.0% each). The mean age of the study population was 51.8 ± 16.2 years. Table 2. Gender distribution of study participants (n = 80) Gender Number (n) Percentage (%) Male 46 57.5 Female 34 42.5 Total 80 100.0 Among the 80 patients, 46 (57.5%) were males and 34 (42.5%) were females, giving a male-to-female ratio of approximately 1.35:1, indicating a male predominance. Table 3. Distribution according to severity of sepsis (n = 80) Severity Number (n) Percentage (%) Non-severe sepsis 48 60.0 Severe sepsis/Septic shock 32 40.0 Total 80 100.0 Out of the 80 enrolled patients, 48 (60.0%) had non-severe sepsis, whereas 32 (40.0%) were diagnosed with severe sepsis or septic shock. Table 4. Comparison of hematological parameters according to severity of sepsis Parameter Non-severe Sepsis (n=48) Mean ± SD Severe Sepsis (n=32) Mean ± SD p-value WBC (×10³/µL) 13.2 ± 3.8 17.4 ± 5.1 <0.001 RBC (×10⁶/µL) 4.32 ± 0.54 3.89 ± 0.49 0.002 Platelet count (×10³/µL) 228.5 ± 68.4 145.3 ± 55.6 <0.001 ANC (×10³/µL) 10.1 ± 3.2 14.6 ± 4.3 <0.001 Immature Granulocytes (%) 1.9 ± 0.8 5.2 ± 1.7 <0.001 Patients with severe sepsis had significantly higher white blood cell count, absolute neutrophil count, and immature granulocyte percentage compared to patients with non-severe sepsis (p<0.001). Conversely, RBC count and platelet count were significantly lower among patients with severe sepsis, indicating greater hematological derangement with increasing disease severity. Table 5. Comparison of biochemical markers according to severity of sepsis Parameter Non-severe Sepsis (n=48) Mean ± SD Severe Sepsis (n=32) Mean ± SD p-value CRP (mg/L) 71.8 ± 28.6 142.6 ± 41.3 <0.001 Procalcitonin (ng/mL) 2.8 ± 1.5 9.4 ± 4.2 <0.001 The mean CRP and procalcitonin levels were significantly higher in patients with severe sepsis than in those with non-severe sepsis (p<0.001). These findings indicate that both biochemical markers are strongly associated with increasing severity of sepsis. Table 6. Receiver Operating Characteristic (ROC) analysis of hematological and biochemical markers for prediction of severe sepsis Marker AUC Sensitivity (%) Specificity (%) Cut-off Value Procalcitonin 0.91 87.5 83.3 >4.5 ng/mL CRP 0.87 84.4 77.1 >100 mg/L Immature Granulocytes 0.89 84.4 81.3 >3.5% Platelet Count 0.82 78.1 75.0 <180 ×10³/µL ANC 0.80 75.0 72.9 >12 ×10³/µL WBC Count 0.76 71.9 68.8 >15 ×10³/µL ROC curve analysis demonstrated that procalcitonin (AUC = 0.91) had the highest diagnostic accuracy for predicting severe sepsis, followed by immature granulocyte percentage (AUC = 0.89) and CRP (AUC = 0.87). Among the hematological parameters, platelet count, ANC, and total WBC count also showed good predictive performance. These findings suggest that combining routine hematological and biochemical markers can improve early prediction of sepsis severity.

The present prospective observational study evaluated the role of routine hematological and biochemical markers in predicting the severity of sepsis among 80 patients admitted with clinically suspected sepsis. The findings demonstrated that patients with severe sepsis had significantly higher total leukocyte count (WBC), absolute neutrophil count (ANC), immature granulocyte (IG) percentage, C-reactive protein (CRP), and procalcitonin (PCT) levels, whereas red blood cell (RBC) count and platelet count were significantly lower than those with non-severe sepsis. These observations suggest that routinely available laboratory parameters can provide valuable information for early risk stratification and prognostication in patients with sepsis. In the present study, the majority of patients belonged to the 46–60 years age group, with a mean age of 51.8 ± 16.2 years, and males constituted 57.5% of the study population. Similar demographic findings have been reported by Vincent et al. (2014), who observed that sepsis predominantly affects middle-aged and elderly individuals, with a slightly higher incidence among males because of a greater prevalence of comorbid illnesses and infection-related hospitalizations.[9] Likewise, Fleischmann et al. (2016) reported increasing incidence and mortality of sepsis with advancing age, emphasizing the vulnerability of older adults to severe infections.[10] The present study demonstrated significantly elevated white blood cell count and absolute neutrophil count among patients with severe sepsis. Leukocytosis and neutrophilia reflect activation of the innate immune response following systemic infection and are among the earliest laboratory abnormalities observed in septic patients. Similar findings were reported by Singer et al. (2016), who highlighted leukocyte abnormalities as an important component of the inflammatory response in sepsis. [11] Gupta et al. (2019) also observed significantly higher neutrophil counts among patients with severe sepsis and concluded that hematological indices obtained from routine hemograms could aid in assessing disease severity.[12] A significant increase in the immature granulocyte (IG) percentage was observed in patients with severe sepsis in the present study. During severe bacterial infections, accelerated bone marrow stimulation results in the premature release of immature granulocytes into peripheral circulation. Several investigators have demonstrated that elevated immature granulocyte counts are useful indicators of bacterial sepsis and correlate with disease severity. Ansari-Lari et al. (2003) first reported the diagnostic value of automated immature granulocyte counts,[13] while Ayres (2013) concluded that immature granulocyte percentage is an effective early marker of systemic bacterial infection and may predict progression to severe sepsis.[14] The present study also found a significant reduction in platelet count among patients with severe sepsis. Thrombocytopenia in sepsis is multifactorial and results from increased platelet consumption, disseminated intravascular coagulation, endothelial activation, and impaired platelet production. Platelet depletion has consistently been associated with poor prognosis and increased mortality in septic patients. Similar observations were reported by Venkata et al. (2013), who identified thrombocytopenia as an independent predictor of mortality in critically ill patients with sepsis. [15] Likewise, Gupta et al. (2019) demonstrated that declining platelet count during hospitalization was significantly associated with poor clinical outcomes.[12]. Among the biochemical markers evaluated, both C-reactive protein and procalcitonin were significantly higher in patients with severe sepsis. CRP is an acute-phase reactant synthesized by the liver in response to inflammatory cytokines, whereas procalcitonin is released in response to systemic bacterial infections and has been recognized as a highly specific biomarker for bacterial sepsis. The higher PCT values observed in the present study agree with the findings of Schuetz et al. (2017), who reported that serum procalcitonin is useful not only for diagnosing bacterial sepsis but also for predicting disease severity and monitoring response to therapy. [16] Similarly, Wacker et al. (2013), in a systematic review and meta-analysis, concluded that procalcitonin possesses good diagnostic accuracy for identifying sepsis in critically ill patients.[17] Receiver operating characteristic (ROC) analysis in the present study demonstrated that procalcitonin exhibited the highest diagnostic accuracy, followed by immature granulocyte percentage and CRP, whereas platelet count, ANC, and WBC count also showed acceptable predictive performance. These findings support previous reports indicating that combinations of hematological and biochemical markers perform better than individual biomarkers in predicting sepsis severity. Pierrakos and Vincent (2010) reviewed more than 170 biomarkers of sepsis and concluded that no single marker is sufficiently accurate for diagnosis or prognosis; instead, combining routinely available laboratory parameters improves clinical decision-making.[18] The findings of the present study highlight the importance of routine hematological and biochemical investigations in the early identification of patients at risk of severe sepsis. Since these investigations are inexpensive, rapidly available, and widely accessible, they may be particularly valuable in resource-limited settings where advanced molecular biomarkers are not readily available. Incorporating these laboratory markers into routine clinical assessment may facilitate earlier diagnosis, timely initiation of appropriate therapy, and improved patient outcomes. Overall, the present study demonstrates that WBC count, ANC, immature granulocyte percentage, platelet count, CRP, and procalcitonin are useful predictors of sepsis severity, with procalcitonin showing the highest diagnostic performance. These findings are consistent with previous literature and support the combined use of hematological and biochemical markers as practical tools for early risk stratification in patients with sepsis.

The present study demonstrated that routine hematological and biochemical markers are effective predictors of sepsis severity and can aid in the early identification of patients at risk of developing severe sepsis. Patients with severe sepsis had significantly higher total leukocyte count, absolute neutrophil count, immature granulocyte percentage, C-reactive protein, and procalcitonin levels, along with significantly lower platelet and red blood cell counts compared with patients with non-severe sepsis. Among the evaluated biomarkers, procalcitonin showed the highest diagnostic accuracy, followed by immature granulocyte percentage and C-reactive protein, indicating their strong prognostic value. Since these investigations are inexpensive, readily available, and routinely performed in clinical practice, their combined use can facilitate early risk stratification, timely therapeutic intervention, and improved patient outcomes. Further large-scale multicenter studies are warranted to validate these findings and establish standardized cut-off values for routine clinical application.

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