Abstract 
Background: Acute pesticide poisoning, particularly from suicide attempts or accidental exposure, is a growing issue, especially in developing countries. This study explores predictive factors for the Length of Stay (LOS) in patients with pesticide-induced thrombocytopenia.
Methods: This cross-sectional retrospective study was conducted at Khorshid Hospital, Isfahan University of Medical Sciences. It included patients aged 18 or older admitted between 2020 and 2021 with acute pesticide intoxication who experienced thrombocytopenia upon admission or during hospitalization, excluding those with significant pre-existing hematological conditions or a history anti-platelet medication. Data was collected on demographics, toxicological features, clinical and laboratory findings, and LOS.  Data were extracted from patients’ clinical records. 
Results: Among the 240 patients studied, the average age was 36.3 years, with a majority being male. Most patients had an LOS of over 72 hours. Significant factors of longer LOS included the type of pesticide (with herbicides and fungicides associated with extended stays), higher white blood cell counts, and lower magnesium levels. There was no significant association between LOS and clinical outcomes. Multivariable linear regression revealed that benzodiazepine administration, and magnesium were associated with reductions in LOS and ICU admission, endotracheal intubation was associated with a longer length of stay (p<0.05).
Conclusion: The findings of this study suggest that targeted treatment with benzodiazepine may reduce hospital LOS. Additionally, monitoring of laboratory data such as WBC and magnesium level could also influence LOS. Future multicenter studies with larger sample sizes are necessary to further evaluate the predictive factors of LOS in these patients.
Keywords: Hospitals, Length of stay, Pesticides, Thrombocytopenia

Introduction 
Pesticides are chemical products used to eradicate various pests and enhance agricultural efficiency (1). They include a wide range of substances such as insecticides, fungicides, herbicides, and rodenticides, which are used globally (2). The use of pesticides has increased significantly over recent decades, particularly in developing countries (3). Pesticides are widely used in Iranian agriculture which has become major toxicological concern among health professionals (4). 
Acute pesticide poisoning is an emerging health issue in many countries, especially in developing nations such as Iran (5). Various studies have demonstrated the adverse effects of pesticides on human health (6). Despite their critical role in food supply, pesticides can impact different organs and cause serious illnesses (7). 
In addition to long-term effects, short-term exposure to pesticides can also lead to complications (8). Many other hematologic changes secondary to acute and chronic pesticide exposure have been documented in both humans and animals, although there are some conflicting results (9). Recent studies have shown that exposure to certain chemicals can result in changes to various hematological parameters. Specifically, there have been decreases in Red Blood Cell (RBC) and White Blood Cell (WBC) counts observed in cases of acute and chronic intoxications (10). 
A review of case reports from 1946 to 1960 indicated that exposure to organochlorines, in particular, can lead to blood dyscrasias. However, it is uncertain whether this relationship is causal (11). Studies have demonstrated that Organochlorine Pesticides (OCPs) can impact the hematopoietic system through immunological mechanisms, potentially causing blood-related disorders (12). As fat plays a crucial role in supporting hematopoiesis, the accumulation of OCPs in bone marrow adipose tissue may elevate the risk of interfering with lymphohematopoietic function (13). Regarding the platelet levels, findings have been inconsistent and controversial, with reports of both thrombocytosis and thrombocytopenia in cases of pesticide exposure (14-19). The mechanism behind drug-induced thrombocytopenia is either a decrease in platelet production (bone marrow toxicity) or an increase in destruction (immune-mediated thrombocytopenia) (20). 
Due to the fact that all the admitted patients experienced thrombocytopenia either upon admission or during hospitalization, it has been proposed that the Length of Stay (LOS) can greatly influence the development of thrombocytopenia in the admitted patients.
LOS defined as the duration a patient remains hospitalized, is a key indicator of patient outcomes. LOS can be influenced by various factors, including past medical history, disease severity, and type of medical interventions (21). However, the predictive factors for LOS in thrombocytopenic patients due to pesticide intoxication have not been thoroughly assessed. This current retrospective cross-sectional study aims to evaluate the predictive factors affecting LOS in patients with pesticide-induced thrombocytopenia.
  
Materials and Methods
This cross-sectional retrospective study was conducted at Khorshid Hospital, affiliated with Isfahan University of Medical Sciences, in Isfahan, Iran. The study adhered to the Declaration of Helsinki on biomedical ethics. Ethical approval was obtained from the Ethics Committee under code IR.MUI.MED.REC.1400.381. 
In unpublished data from the center 240 patients with acute pesticide poisoning, who had no history of platelet abnormalities, experienced thrombocytopenia either upon admission or during hospitalization. 
All the patients aged 18 or older were admitted to the referral poisoning center of Khurshid Hospital due to acute pesticide intoxication from 2020 to 2021 who experienced thrombocytopenia during hospitalization and were included in the current study. Inclusion criteria required no prior history of hematological conditions (especially coagulopathies or other platelet disorders), no history of anti-platelet medication before hospitalization and no somatic disease in the previous weeks.
Patients with incomplete data in their medical records or discharged due to personal consent or other non-medical reasons leading to early discharge were excluded.

Data collection
Data were collected using a data gathering form comprising various sections: demographics, toxicological features, clinical and laboratory findings, and clinical measurements. The demographic section included variables such as age, sex, place of residence, education level, and marital status, season of toxicity and place of intoxication. The toxicological section covered the type of pesticide, route of poisoning, and the time interval between poisoning and hospitalization. Clinical and laboratory findings included vital signs, lab tests including CBC (WBC, RBC, HB, HCT, PLT), BUN, Cr, LFT (AST, ALT, ALP, total and direct bilirubin), BS, electrolytes (Na, K, Ca, phosphorus, Mg), coagulation tests (PTT, PT, INR), and clinical outcomes, including length of stay and indication for intubation or dialysis were recorded. All the protocol treatments were recorded. 
 Data were extracted from patients’ clinical records. Two researchers collected the data under the supervision of an attending toxicologist. Diagnosis of intoxication was made by expert attending physicians based on clinical examination, vital signs, self-reported history or information from relatives, and clinical laboratory tests or urinary toxicological analysis when necessary.

Definitions
Pesticide intoxication is defined as any intentional or unintentional exposure to insecticides, herbicides, rodenticides, or other pesticides, regardless of clinical manifestations. Thrombocytopenia is defined as a platelet count of less than 150,000/µL in a Complete Blood Count (CBC) result upon admission. The patients were categorized into three groups based on their length of hospital stay: less than 24 hrs, 24-72 hrs, and more than 72 hrs. The severity of manifestations varies with the degree of poisoning (22).

Statistical analysis
SPSS 26 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Continuous variables were described by mean and standard deviation, while the categorical variables were described by frequency and percentage. Chi-square or Fisher exact tests were used for categorical data to assess between-group differences. Independent samples test and analysis of variance (ANOVA) were used for normally distributed continuous variables to assess between-group differences. Linear regression was used to evaluate the factors influencing the length of stay. Protocol treatments were categorized for linear regression as: Antidotes (pralidoxime, atropine), Antiapoptotic agents (vitamin C, vitamin E, corticosteroids) and Benzodiazepines (diazepam, midazolam) and antiacid (ranitidine, pantoprazole). 

Results
A total of 240 patients were assessed in this study. The most frequently encountered pesticides among patients were insecticides (n=100), herbicides (n=57), rodenticides (n=66) and others (n=12), respectively. The mean age of the patients was 36.3±16.78 years. The gender distribution revealed a higher frequency of male patients, with 186 (77.5 %) males. The patients were categorized into three groups based on their length of stay. The majority of patients (123, 53.1%) were in the group with a stay of more than 72 hrs. Table 1 presents the toxico-epidemiologic characteristics and medical history of patients categorized by length of stay. There was a significant difference between the three groups in terms of types of pesticides. Patients in the herbicide and fungicide groups experienced longer hospitalizations. However, there were no significant differences between groups regarding other toxico-epidemiologic and demographic variables. There were also no significant differences between groups concerning physical illnesses, psychiatric disorders, or self-harm history. However, it is also worth noting that there were significantly higher frequencies of prolonged hospitalization among the patients with severe toxicity.
Results are expressed as numbers (percentages) or mean±standard deviation (SD). Categorical variables were analyzed between groups using Fisher’s exact test or Chi-square test. *According to the post hoc analysis, a significant difference was observed between group 3 (more than 72 hours) and other groups 
Therapeutic interventions and clinical outcomes were also compared between groups as shown in table 2. Patients with longer lengths of stay exhibited a higher frequency of requiring various treatments, including dialysis, ICU hospitalization, and intubation. Additionally, medications such as pralidoxime, atropine, NAC, vitamin C, vitamin E, Corticosteroids, pantoprazole, and KCl were significantly more frequently administered to the patients in the group that stayed more than 72 hrs. There was no significant association found between clinical outcomes and length of stay. 
The statistical analysis revealed no significant differences between the groups for most laboratory findings. However, significant differences were observed in WBC count and magnesium levels among the three studied groups. Patients in the “over 72 hrs” group exhibited significantly higher WBC and lower magnesium levels.
Factors associated with LOS were examined using a multivariable linear regression model in table3. Benzodiazepines were found to reduce in LOS by 20 min, while antibiotic administration was associated to an increase in LOS by 20 min. Intensive care unit duration was also linked to an increase in LOS by 16 minutes. Furthermore, for every 1 mg/dL increase in blood magnesium levels, the length of stay decreased by 3 min (p<0.05). 

Table 1. The comparison of toxico-epidemiologic and medical history variables between groups based on the length of stay