Sepsis is thought to impact more than 30 million individuals worldwide each year, potentially leading to 6 million fatalities. According to the most recent global estimates for sepsis incidence and mortality, based on data for individuals admitted to hospitals in seven high-income countries, 19 and a half million new cases of sepsis occur each year and Around 5 million people die from sepsis-related causes [1]. Numerous studies conducted in both developed and developing nations have demonstrated that sepsis mortality is high and associated with delayed diagnosis, late treatment, and non-adherence to recommended treatment regimens. Sepsis mortality reduction is a global challenge [2]. Severe organ dysfunction, hypotension, septic shock, and mortality are all symptoms of sepsis, and a constellation of multiple pathophysiological abnormalities that develop as a result of an aggressive host response to infection[3-4].

Growing research demonstrates how platelets, in addition to their function in hemostasis and thrombosis, play a crucial role in inflammation, microbial host defence, healing, angiogenesis, and remodelling. When platelet granules produce proteins, some of these proteins have an impact on the way immune cells and vascular walls function, while others have microbic and antibacterial capabilities. They also play a crucial role in the production and release of vascular endothelial growth factors, that are implicated in malignant tumorigenesis in addition to inflammation[5-6]. Platelets have been referred to as "essential players" in sepsis because they interact with endothelial cells and affect the outcome.[7]

Platelet indicators include the mean platelet volume (MPV), a measure of platelet size, the plateletcrit (PCT), a calculation of the total mass of the platelets, and the platelet distribution width (PDW), which rises with accelerated platelet turnover[8]. Other indicators include the platelet large cell ratio (PLCR), and platelet volume distribution width (PDW). MPV changes have already been describedin some infection, such as acute appendicitis, pancreatitis, infective endocarditis, and malaria. However, the evidence in sepsis and septic shock is currently controversial—some studies suggest that MPV increases during septic shock, while others show a decrease. The PDW increases during acute severe infections when turnover is increased during platelet depletion. The amount and size of platelets have an impact on the plateletcrit (PCT)[9]

All complete hemogram reports usually include platelet indices, which are a conveniently accessible haematology investigation. They are perfect for low-resource situations since they are affordable, need minute sample volumes, and have rapid turnaround times. Simple arithmetic can be used to estimate changes in platelet indices over time. When repetitive serial measurements are necessary, complex assays place an unfair burden on the healthcare system. Hematological indicators that are straightforward and affordable have an enormous significance. In order to evaluate whether platelet count and platelet indices (PDW, MPV, PCT) could be utilised to assess disease severity and predict outcomes in critically ill adult patients, the current study was undertaken.

^.AIMS AND OBJECTIVE

To explore whether platelet count and platelet indices could be used to determine the severity of illness to predict the prognosis in sepsis patients.

STUDY DESIGN

This cross sectional-observational study was conducted at a tertiary care center in northern India. 140 cases and 70 controls were included between October 2020 and October 2022. In both groups, patients were analysed as survivor or non-survivors based on the outcome. Sepsis was defined according to the third International consensus for sepsis (Sepsis-3). Demographic information including age, sex, comorbidities (HTN, CKD, COPD, Diabetes, CAD) was collected. Patient with known or suspected infection were assessed using SIRS and SOFA score. Clinical assessment included body temperature, pulse rate, respiratory rate, GCS, and mean arterial pressure. Blood investigations were performed within 48 hours of admission or at the time of diagnosis of sepsis (in subjects without sepsis at the time of admission) and included TLC, Hb, platelet indices (including  platelet count, MPV, PDW, PCT), serum creatinine, and bilirubin. Blood samples for CBC were collected in EDTA vial while for LFT, RFT, procalcitonin were collected in plain vial. ABG analysis was performed to assess the PF ratio and serum lactate. The indices were reassessed at the time of outcome.

INCLUSION and EXCLUSION CRITERIA

Patients with age more than 18 years, admitted in ICU setup and fulfilling sepsis criteria and definition were cases. Controls were patients who were not fulfilling criteria for sepsis but were admitted to ICU setup for some other illness. Patients with active hemorrhage, pregnancy, recent blood/platelet transfusion (within 15 days), on antiplatelet drug, with known hematological diseases (including anemia not due to the present illness, hypersplenism, lymphoma, leukemia, rheumatological or bone marrow diseases) were excluded.

STATISTICAL ANALYSIS

Statistical analysis was done using SPSS version 16.0. Continuous variables are expressed as mean ± SD or median and categorial variables as percentage. Chi-square and Fischer exact test were used for analysing categorical variables. Paired t test was used for 2 groups with continuous variables. ROC curves were generated for different indices to predict mortality.

A total of 210 patients (140 cases and 70 controls) were analysed. Among baseline parameters, pulse rate, respiratory rate, total leucocyte count, PLT and PDW differed significantly in sepsis patients as compared to the controls (table 1). Patient with sepsis had tachycardia, increased total leucocyte count, lesser platelet count, with higher PDW (17.24 ± 1.30 vs 16.57 ± 0.67 p<0.0001). The duration of hospitalisation did not differ significantly between the two groups (11.68  9.08 vs 9.52  5.19 days, p value=0.073).

Comorbidities in the study subjects included hypertension, Type 2 diabetes mellitus, CKD, COPD

SIRS was present in 92% of cases vs 42% of controls (p value=0.001). However, it was not associated with increased mortality (91.5% in non-survivors vs 92% in survivors). Among non survivors 31% had ARDS as compared to survivors where 23.3% had ARDS. Overall, mortality was greater in patients with sepsis than those without (51% vs 20.9% p<0.001).

Overall non-survivors were found to have higher respiratory rate, lactate, SOFA score, and a lower GCS at baseline, but a lower platelet count, plateletcrit and higher PDW at outcome (table-3).

Receiver operator curves

ROC curves for baseline platelet indices are presented in Figure-2. PCT had the highest AUC (0.602) and therefore, was the best mortality predictor at optimum cut off of 0.131% with sensitivity of 56.5% and specificity of 60%. Other indices had lesser AUC, in decreasing order of PDW>PLT>MPV (Table-8)

Table 1. Baseline parameters in cases vs controls

Table 2. Comorbidities in sepsis patients

Table-3

Table-4

Table-5 (AUC for ROC for platelet indices at baseline as a predictor of mortality)

The present study was conducted at Department of General Medicine, Sir Sundar lal hospital, in collaboration with the Department of Pathology, Institute of Medical Sciences, Banaras Hindu University. A total of 140 patients along with 70 controls were enrolled in the study after taking informed consent from the patients or their attendants.

SIRS was present in 92% in cases vs 42% in controls (p value0.001) but among the patients with sepsis, SIRS was not associated with increased mortality(91.5 % in non survivor vs 92 % in survivor). In another study, in patients with sepsis-3 defined organ dysfunction, SIRS was present in 1,561 patients (72.1%), and associated with increased mortality (OR 2.2; 95% CI, 1.5–3.1) in David Andaluz¹, Ricard Ferreret al study[10]

In our study presence of ARDS and MAP< 65 both were associated with increased mortality amongst sepsis patients. Studies show that the 28-day mortality rate was higher in patients with sepsis and ARDS (64%) compared to those without ARDS (9%)[11]. These data were confirmed by Eggimann P, Harbarth S, Ricou Bet al in a study performed in Switzerland where they found patients with sepsis and ARDS had shorter survival rates than those without ARDS (58% vs. 31%, respectively) [12].Similarly, mean arterial pressure (MAP) < 65, requiring vasopressor support was present in 45% of non survivors as compared to 20% in survivors with statistical significance(p value 0.025).

In the present study changes in platelet indices with time varied significantly between survivor and non-survivor. A distinctive pattern of variation was observed during the course of hospitalisation which could be used for predicting the clinical outcome and also guide medical intervention. We found PLT and PCT can be helpful in identifying patients with sepsis from other patients in ICU setup on the basis of baseline parameters. But at baseline or within 48 hours of admission or at the time of sepsis diagnosis none of these platelet indices were significantly different among survivors and non-survivors, which shows that we cannot relate these parameters to outcome in early course of illness. Though not significant PDW had greater elevations in non-survivors similar to study of S. V. R. Raja Sekhar et al [13] and Akarsu's et al research in neonates with sepsis.[14]. Similarly, PLT and PCT were lower in non survivors at baseline.

Conflicting data exists for MPV in sepsis, as some studies report a lower level of MPV in non survivors [15] while others show complex patterns of MPV changes in the form of initial rise followed by decrease in MPV in sustained bacterial infection. In all 10 patients MPV fell as the platelet count rose. The peak platelet count was 212 + 63% (mean ± SD) of baseline platelet count and the minimum MPV was 80.2 ± 5-1% (mean + SD) of baseline MPV. On an average the peak platelet count occurred 10 days after the onset of infection and the lowest MPV was observed one day after the peak platelet count.[16]

Thrombocytopenia due to decreased production or increased production is a well known consequence of sepsis. Increased platelet activation and prothrombotic potential may lead to increased aggregation in circulation[17]. Both platelet count and PCT did not differ significantly at time of admission but showed decreasing values in non-survivors and increasing trend in survivors[18-22].

In previous studies thrombocytopenia developed in 145 patients (47.6%); 77 patients(25.3%) had low platelet count at the time of ICU admission and an additional 68 (22.3%) patients developed thrombocytopenia during their hospital course[22]. Although persistent thrombocytopenia is associated with worse outcomes, a single initial platelet count does not discriminate survivors from non-survivors[22,23]

At the most imminent time of outcome three parameters, viz. lower PLT (112K ± 98K vs 225K ± 133K), higher PDW (17.52 ± 1.58 vs 16.74 ± 0.84), lower PCT (0.113 ± 0.10 vs 0.21 ± 0.13) were present in non-survivors which was statistically significant compared to survivors, in accordance with findings in a previous study [18].

A higher PDW suggests platelet heterogeneity, which is attributed to platelet swelling and immaturity. The present study shows increasing PDW values with time in non survivors and a decreasing trend in survivors which is in agreement with other studies[18].

Using ROC curve analysis, PCT was found to be the best mortality predictor with sensitivity of 56.5% and specificity of 60% at an optimum cut off of 0.131%. According to a previous study, among the platelet indices, MPV was the best mortality predictor, with an AUC of 0.825 and an optimum cut-off of 10.25 fL with a sensitivity of 93.9% and specificity of 60.9%[18].

 LIMITATIONS

Although, changes in platelet indices were associated with sepsis but a cause-effect relationship could not be elicited by this study. A deeper analysis of kinetics of platelet indices would provide a better assessment of platelet indices and mortality. Long term outcomes or mortality cannot be analysed by this study. Thus, a prospective study with larger sample size can provide better assessment.

In previous studies, focus was mainly on platelet indices within 72 hours, but the present study assessed absolute values at baseline and at the time of outcome, thus displaying a trend between two extreme points of study. It also assessed other predictors for mortality and found higher lactate levels, respiratory rate, SOFA score, and a lower GCS to be associated with increased mortality. Platelet indices are easily and readily available parameters for clinicians even at resource limited facilities. They are cost effective and can be availed at multiple times during hospitalisation with immediate results. These changes in platelet indices can be understood with simple arithmetic.

Thus, application of trend of changes in these indices over course of hospitalisation can be of great significance for timely intervention and prognostication.

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