Background: Burn injuries are a major cause of morbidity and mortality, because of the severe local and systemic response developed, affecting organics functions. A decline in platelets and lymphocyte count compromise the immune response and patient´s outcome. To evaluate the usefulness of platelet to lymphocyte ratio as a biomarker of mortality in severely burned patients, the present research was performed.

Methods: A descriptive, longitudinal, prospective study was carried out at the Burn Department of Calixto García Hospital, La Habana, from January 2022 to December 2023. All admitted patients with major burns, ages between 19 and 60 years old, and less than 24 hours since the beginning of the trauma, were included. Blood samples were taken on days 3 and 6 after injury, to determine platelet to lymphocyte values, and a relationship between the mortality rate and presence of complications was established.

Results: 143 burned patients were included, males were predominant (63 %), flame (98.2 %) was the first causal agent and accidents (89.6 %) were the main production mode. 90 % of patients survived. Platelet-to-lymphocyte ratio values were lower in patients who developed complications and in the nonsuvivors group.

Conclusions: Platelet to Lymphocyte ratio is an effective biomarker for predicting mortality in severely burned patients.

Keywords: Burns, inflammation, lymphocytes, platelets

Burn injuries are a major cause of morbidity and mortality, representing a global health problem, affecting not only the skin, but besides developing an important local and systemic inflammatory response, with harmful effects in most of the organs and system of organs.¹ The severity of the burn injury is a determining factor for patient´s prognosis. Despite the advancement in therapeutic protocols, including hydric resuscitation, early debridement of burned tissue, skin grafting, and enteral nutrition, the incidence of mortality rates and complications are still remarkable.²

Major Burn causes significative changes in haematological parameters marking the final evolution of the disease.³ White blood cells are the first defense line against injuries, and are seriously affected after a thermal trauma.^4,5 Disorders in leukocytes, mainly in lymphocyte count and functions have been described.^5,6 Lymphocytes (B and t), are one of the main immune cells with essential function for a normal host response, originating in the bone marrow, and circulating in peripheral blood and lymphatic tissue, playing a determinant role in both, innate and humoral immune response.⁷ A decline in lymphocyte count, (lymphopenia), suggests an Inflammatory process and immunosuppression.^6,7 A redistribution of lymphocyte cells following an extensive burn injury, with a disruption of the balance between T cells (helpers and suppressive) seems to produce disturbances of the adaptative immune response.⁸

Platelets or Thrombocytes are anucleated small blood cells, that originated in bone marrow from the megakaryocytes series, having a crucial role in thrombus formation, hemostasis and wound healing.⁹ They have been recognized to be closely involved in the burn injury physiopathology, by inducing cytokines and epidermal growth factor (EGF) release, and several Inflammatory mediators.⁸ Platelets count are useful as an acute biomarker for predicting sepsis, thrombotic complications and mortality in the major burn. Thrombocytopenia is considered a risk factor for septic shock in burns. Platelets are consumed in the endothelium of the damaged burned skin, affecting the function (margination), hemostasis and healing.^5,6

During the last decades numerous researches have been developed to find out non-invasive and effective diagnostic tools for the early detection of complications in severely burned patients. Utility of different Inflammatory biomarkers as Protein C Reactive (PCR), Procalcitonin, and Neutrophil to Lymphocyte Ratio (NLR), have been widely studied in burn trauma.^9-12

Platelets to lymphocytes ratio (PLR) is defined as the ratio of platelets count to lymphocytes count, and can be calculated quickly and inexpensively from a routine complete blood count,^13,14 which is performed in most the locations of the medical, using automated equipment for haematic cytometry.¹⁵ PLR has been demonstrated to play a role as a marker of acute inflammation in differents conditions as: Breast and Lung cancer, Covid – 19 infection, neonatal sepsis, Cardiovascular diseases and traumas.^16-21

 As a new biomarker, PLR has been described as the combination of two hematological parameters, providing the concept of Inflammatory cascade and platelet aggregation.²² An improvement in the understanding of changes in blood cell series and derivated indexes as PLR, following a burn trauma, provides a tool for a rational and efective use of immunomodulator drugs.^22,23

There are no previous published studies in the country reporting the determination of PLR levels in burned patients; and being the inflammation is the physiopathological axis of the burn disease, there is a requirement to identify accessible biomarkers to predict the earliest clinical manifestations of complications or mortality in severe immunocompromised burned patients. To evaluate the usefulness of platelet to lymphocyte ratio in the evolution of the major injury, the present study was performed.

A descriptive, longitudinal and prospective investigation was carried out at the Burn Department, of ¨¨Calixto García Universitary Hospital¨¨, La Habana, Cuba, from January 2022 to December 2023, to evaluate the predictive value of the Platelet to Lymphocyte ratio as a biomarker, in severely burned patients. All admitted patients fulfilling the selection criteria, were studied.

Inclusion criteria

1. Burned patients with body surface area affected ≥ 20 % (Major Burns).
2. Ages between 19 – 60 years old.
3. Admitted patients with less than 24 hours since the beginning of injury.

Exclusion criteria

1. Burns associated with other’s traumas.
2. Immunodeficiencies conditions and coagulopathies, cancer.
3. History of medication intakes: aspirin, warfarin.
4. Patients who died before the 6 th day of evolution.

Data collection

Medicals records were fulfilled, and clinic findings were closely measured. Vital Signs were taken daily, including: Blood Pressure, Urine output, Cardiac and breathing rhythm.

Treatment of the Burn Wound: Extension and deepness of the burn were diagnosed. Burn Extension (Total Body Surface Area) ≥ 20 % were considered major burns. Change of dressing and wound swabs were performed daily.

Complete Blood Counts, Platelets Counts, Chest X-rays, microbiological cultures, and Electrocardiographics studies were performed 3 times per week, to detect complications.

To determine PLR values, blood samples (10 ml of venous blood) were taken at days 3^rd and 6^th after burn trauma, (considering that a calculated fluid reposition is performed during the first 6 days). Samples were centrifugated at 3000 rpm for 15 minutes. All were analyzed at the Central Laboratory of Calixto García Hospital. The cut-off value for PLR was: 71.4.

A relation between PLR values and the discharge status was established.

Statistical analysis

Data were collected from medical records. Analysis of data was carried out using Excel and SPSS software versión 20.0 for Windows, with 95 % CI. The non parametric test (Wilcoxon) was performed to find statistical significance (p<0.005) of quantitative variables. The Media Values (X) and Standards Derivation. (SD) were calculated.

Ethics aspects

The present study was carried out following the standards ethics issues for human research, according to the Helsinki Declaration, Fortalezza, Brasil, 2013. The consent signature of every patient was confirmed by researchers.

Of a total of 216 admitted burned patients, 143 were included. Table # 1 shows the demographic distribution of the sample.

Males were the predominant group. (63 %). Aged group between 30 and 49 years old is the most affected. (71 = 49.6 %). Accidents were the main production mode (128= 89.6 %), followed by 14 suicides (9.8 %) and 1 homicide (1 = 0.6 %).

Figure # 1 shows the etiological agents found.

Figure 1 Etiology of Burns. January 2022-December 2023.

Flame was the first causal agent (69 = 98.2 %), followed by scald burns (37 = 25.8 %). Figure 2 shows media (X) values of Platelet to Lymphocyte Ratio at day 3^rd after burn injury, and its relation with the discharge status.

Figure 2 Discharge Status and PLR.  Day 3^rd after burn injury.

PLR cut off value =71.4, p= 0.02

130 patients (90 %) were discharged live, and 13 (9,09 %) did not survive. PLR Media (X) ± SD values at day 3^rd after burn, were lower (40.5 ± 18.6) in non survivors than in survivors (89.92 ± 22.9). p< 0.05

Table 2, exhibits the PLR values (Media ± Standard Derivation) on day 6 th after burn trauma and its relation with the discharge status. A permanent decline of PLR was observed in patients who died. (p<0.05).

Table 3 exposes the incidence of complications and its relation with the discharge status. A 100 % of studied patients developed wound infection. The incidence of complications was higher in nonsuvivors.

Different biomarkers have been described to predict complications and mortality in severe burn trauma, but during the last decades, a new group of hematological indexes has been recognized as the earliest and useful inflammation markers, including Platelets to Lymphocyte ratio and Neutrophil to Lymphocyte ratio.⁹ Systemic Inflammation in severely burned patients can lead to a decline in platele count and a neutrophilic sequestration in organs with suppression of an immune response, causing lymphopenia.^24,25 In the present research, low values of platelet to lymphocyte ratio were found since the first 72 hours after trauma, in all burned patients studied, being lower in those who did not survive. On the day 6 th after injury recovery of the PLR levels was not obtained in patients who died (p < 0.05).

A similar correlation was demonstrated by Angulo et al.,¹³ in a retrospective study of 88 adult burned patients, with a Media PLR value lower than 60.28 in non-survivors, suggesting that PLR can predict survival in adults with thermal injuries.

According to Del Carpio Orantes,²⁶ PLR is a useful parameter for predicting prognosis in diseases affecting immune response. Hussein et al.,²⁷ described the role of platelet count in predicting outcome in a sample of 30 burned patients, finding thrombocytopenia since the first hours after trauma in dead patients.In the present study, a permanent decline in platelet counts associated with lymphopenia in non survivors patients, was a crucial factor in obtaining a low PLR level even after an adequate hydric reposition.

Djordjevic²⁸ claims that PLR, NLR and Monocyte to lymphocyte ratio may help to identify mortality in critically ill patients, revealing the absence of a proinflammatory state in immunocompromised conditions.

 Aggarwall et al.,²⁹ carried out a prospective investigation in a group of 90 pediatric burned patients, finding lower levels of PLR in children who developed sepsis and in those who did not survive. Their results confirm our findings.

A low PLR was associated with high short-term mortality in severe trauma patients, according to Kim et al.,³⁰ who reported in their study of 139 adults no- burned patients, lower PLR values in the expired group, in comparison to the survivor group.

According to Cato et al.,³¹ an important diminish in platelets count occurs on the 3^rd day after an extensive burn, and a slight recovery of the values can be seen a month after trauma.

Nhorigheimasi and colleagues,³² in a review article claim that PLR helps indicate a shift in platelets and lymphocyte counts in acute inflammation.

In some other conditions the values of PLR remain high,^20,33 revealing differences in the type of Inflammatory response in comparison to the major burn. Infection remains the main cause of mortality and complication of burn injury.³⁴ Most of the published investigations of burn diseases confirm the growth of germens in the wound.^11,12,34 Our results also exhibit a higher incidence of complications, including systemic infections in patients who died.

Extensive burns are still a therapeutic challenge because of the important immunosupression secondary to the systemic Inflammatory response and releasing of several mediators.³⁵ Understanding the pathophysiology behind these biomarkers, including PLR, could result in earlier intervention and improve outcome among burn patients.

A limitation of the present research was the short time studied. We consider that further investigations and comparative studies should be performed to obtain more efficient results. Conclusions: Since the first 72 hours after trauma, a diminish in PLR values was found in burned patients who did not survive, and a recovery of the values was not seen at day 6^th of evolution. Platelet to Lymphocyte ratio is an effective biomarker for predicting mortality in severely burned patients.

None.

None.

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