Diagnostic Utility of Platelet - Lymphocyte Ratio in Adults with Sepsis: A Case - Control Study

Introduction

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.¹ It is a major cause of morbidity and mortality worldwide, despite the advancements in its pathophysiology and therapeutic interventions. Previously, Systemic Inflammatory Response Syndrome (SIRS) was used for detecting the presence of a dysregulated host response. Presently, the Sequential Organ Failure Assessment (SOFA) (originally the Sepsis-related Organ Failure Assessment) is the scoring system used for the categorization of sepsis.

In the recent years, studies have reported the crucial role played by lymphocytes and platelets in the inflammatory process, and the platelet-lymphocyte ratio (PLR), a novel inflammatory marker, has drawn the attention of researchers. PLR may act as an indicator of inflammation in a wide spectrum of diseases like myocardial infarction, acute kidney injury, hepatocellular carcinoma, and nonsmall-cell carcinoma.^2,3

Studies have been conducted to demonstrate PLR as a predictor of mortality due to sepsis, but there are no studies available on its diagnostic utility in sepsis. Therefore, in the present study, we aimed to fill this gap by performing a study on adults with sepsis, in the Indian population.

Materials and Methods

The study included patients admitted to the Father Muller Medical College Hospital, Mangalore, Karnataka, India, in 2019, who had been diagnosed with sepsis on the basis of clinical examination and whose blood sample had been sent for culture. Blood culture was considered as the gold standard test in our study. The patients were divided into 2 groups– blood-culture positive and bloodculture negative, based on the culture results.

The blood samples were examined using a Beckman Coulter (LH 750) analyzer. The haematological parameters, platelet, and lymphocyte counts, on the day of admission, were used for the calculation of PLR. The absolute lymphocyte and platelet counts provided by the Coulter were used. In case of discrepancy, the manual platelet value obtained through the blood smear method was taken into consideration. The PLR was obtained by dividing the absolute lymphocyte and absolute platelet counts.

As the difference in the mean between the two groups was insignificant, the area under the curve (AUC) and optimal cut-off value could not be determined using the receiver operating characteristic (ROC) curve, and the sensitivity, specificity could not be determined.

Inclusion Criteria

Case Group:

1. All patients >18 years of age.

2. Hospitalized patients with culture-positive blood.

Control Group:

1. Hospitalized patients with culture-negative blood.

Exclusion Criteria

1. Patients diagnosed with malignancy; autoimmune diseases; and chronic inflammatory diseases like tuberculosis and connective tissue disorders which altered the PLR.

2. Patients with prior antibiotic therapy.

3. Patients with congenital heart disease.

4. Patients on antiplatelet drugs.

5. Concomitant illnesses like malaria, dengue, or any other viral fever.

6. Culture-positive blood report with the skin commensal identified.

Statistical Analysis

Sample size: Each group consisted of 76 patients.

Z_α =1.96 at 95% C.I Z_β =1.281 at 90% power 

Study design: Observational descriptive study

Plan for data analysis

The data was entered into Microsoft Excel 2016 worksheet following which the statistical analysis was carried out on IBM SPSS version 23, using the mean, standard deviation, and t-test. A P value of <0.05 was considered statistically significant.

If the variation in the mean values between the two groups was significant, then the AUC and optimal cut-off value were plotted using ROC curve, and the specificity and sensitivity were determined.

Results

Each group comprised 76 patients – Group A: culturepositive and Group B: culture-negative patients. The mean age of the patients in groups A and B was 58 years and 53 years, respectively. In both the groups, the number of male patients was more than that of female patients.

Majority of the cases in group A were diagnosed with urosepsis, and the culture contained E. coli bacteria in most cases.

Discussion

Sepsis is a life-threatening condition caused by dysregulated host immune response to infection. Due to the various forms of clinical presentations of sepsis, even experienced clinicians find it very difficult to diagnose sepsis, although basic clinical examination findings and routine lab work are able to indicate the presence of inflammation and organ dysfunction. Currently, the SOFA is in use to quantify sepsis. A high SOFA score is indicative of an increased risk of mortality.

The use of PLR in research related to sepsis is new. There is a decrease in the platelet count during sepsis. This could be due to decreased platelet production in the bone marrow which can result from pre-existing conditions or from the inhibitory effect of pathogen toxins, drugs, or inflammatory mediators on hematopoiesis.⁶ Sepsis also causes a decrease in the number of circulatory lymphocytes due to apoptosis via death receptor and mitochondrial pathways.⁷ The concept of using PLR in the diagnosis of sepsis is still emerging and needs to be explored further through more studies, which encouraged us to conduct the present study. Some of the previous studies only estimated PLR as a predictor of mortality due to sepsis, and it was also compared with other parameters.

Shen et al studied the prognostic role of PLR in septic patients wherein the data of 5537 ICU patients was collected retrospectively. Further subgrouping was done based on vasopressor use, acute kidney injury (AKI), and SOFA score. Their results showed that PLR >200 was significantly associated with mortality and PLR <200 was not found to be significant. In the subgroups comprising patients with vasopressor use, AKI, and SOFA score >10, the association between high PLR and mortality was not significant when compared to those with SOFA score <10 where the association was found to be significant. They concluded that high PLR was associated with an increased risk of mortality.²

Menezes et al aimed to assess the PLR as a predictor of mortality in sepsis. Retrospectively, the data of 195 ICU patients with septic shock was studied in detail. The cutoff value for PLR was 8 in this study, and the patients were grouped as PLR<8 (low PLR) and PLR>8 (high PLR). The area under the ROC curve was plotted to know the accuracy of PLR in predicting mortality. The mortality period of patients with low PLR was 4 and 28 days, respectively, indicating low LPR to be associated with mortality.⁵

Biyikli et al and Duman et al compared the admission lactate levels and the PLR among the deceased and surviving patients >65 years old, who had been diagnosed with septic shock. Various other parameters like systolic blood pressure, diastolic blood pressure, and Glasgow Coma Scale were studied. They failed to demonstrate any statistical significance in the lactate levels and PLR in septic patients.³

In our study, the majority of the patients in both the groups were in their 5th decade of life. In both the groups, the male gender outnumbered the female gender. As far as the clinical diagnosis was concerned, majority of the patients in group A presented with urosepsis. Some of the other diagnoses included typhoid, pneumonia, and uremic encephalopathy to name a few. E. coli was found to be the cause of sepsis in majority of the culturepositive cases. However, the PLR was not found to be statistically significant. Due to this, the optimum cut-off value for differentiating between the two groups could not be derived and hence, the sensitivity, specificity, positive predictive value, and negative predictive value could not be determined.

Study limitations

The small sample size and retrospective collection of the data could have led to missing out a few exclusion criteria. Some of the exclusion criteria, such as ruling out patients who were on antiplatelet drugs, were difficult as the information would not have been documented in the discharge summary. This study could have been conducted prospectively, to avoid missing out on the important parameters, be it inclusion or exclusion. The sample size also could have been increased. Also, there were no previous studies for comparison, as this study was the first of its kind.

Conclusion

Despite the significant advancements in the diagnosis and treatment of sepsis, its mortality rate remains high. As there is no single specific test for the diagnosis of sepsis, further studies are required to establish the diagnostic utility of PLR in patients with sepsis.

Conflicts of Interest

Authors declare that there is no conflict of interest.