Dengue fever, a rapidly spreading mosquito-borne viral disease, poses a significant public health challenge globally. It is estimated that around 50 million infections occur annually across 100 endemic countries, with a 30-fold increase in incidence observed over recent decades. The disease's geographic expansion has brought new areas under its influence, including rural regions previously unaffected [1]. The World Health Organization (WHO) regions of the Americas, Southeast Asia, and the Western Pacific are particularly burdened, accounting for nearly 75% of the global disease load. In these regions, dengue fever has transitioned from being an urban and peri-urban phenomenon to affecting rural areas as well [2].

The disease is characterized by its epidemiological patterns, hyperendemicity, and the circulation of multiple dengue virus (DENV) serotypes. Four primary serotypes, DENV-1, DENV-2, DENV-3, and DENV-4, are known to cause clinical illness, with a fifth serotype, DENV-5, identified more recently [3]. Dengue infection can manifest in a range of clinical forms, from asymptomatic to severe cases, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which can be fatal.

India has experienced a notable increase in dengue cases, with significant outbreaks reported in recent decades [4]. The disease's prevalence has expanded, with 35 states affected in a major outbreak in 2015. The National Vector Borne Disease Control Programme (NVBDCP) data shows fluctuating but generally increasing numbers of cases and deaths over the years, with the highest number of cases reported in 2017. The seasonal pattern of dengue, with a peak following the monsoon season, adds complexity to its management and control efforts [5].

Dengue fever's clinical manifestations include a range of symptoms such as severe headache, retro-orbital pain, myalgia, arthralgia, rash, and mild hemorrhagic signs [6]. Severe forms of the disease can lead to complications like plasma leakage, bleeding, and organ impairment. Haematological and biochemical changes are common, with leukopenia, thrombocytopenia, and elevated liver enzyme levels often observed [7].

The present study focuses on the haematological profile of patients with dengue fever, aiming to explore the correlation between haematological parameters and the severity of the disease. Understanding these dynamics is crucial for improving diagnostic accuracy and guiding clinical management [8]. By examining haematological markers, this study seeks to provide insights that could enhance the screening and monitoring of dengue patients, ultimately contributing to better health outcomes.

Place of Study: The study was conducted at the Department of Internal Medicine, Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Burla.

Period of Study: The study covered a period of two years, from November 2017 to October 2019.

Study Design: This research is a hospital-based observational (descriptive) study.

Study Group

Inclusion Criteria:

1. All patients admitted to the dengue ward and general medicine wards with:

• Serum NS1 antigen and/or IgM antibody positive by ELISA.
• Age over 14 years.

Exclusion Criteria:

1. Patients co-infected with dengue and malaria, as determined by MP-QBC/Slide Test.
2. Patients with pre-existing conditions such as chronic kidney disease, chronic liver disease, sickle cell disease, or thalassemia.

Case Definition

• Dengue without Warning Signs: Patients with fever and NS1 and/or IgM positive by MAC ELISA, without signs of CNS dysfunction, persistent vomiting, abdominal pain, hemorrhage, fluid accumulation in the body, cold clammy skin, hypotension, or features of congestive heart failure (CCF) or respiratory distress.
• Dengue with Warning Signs: Patients positive for NS1 and/or IgM by MAC ELISA plus any of the following:
1. Persistent vomiting (more than 5 times in 6 hours, more than 2 times in 1 hour, or more than 1 time for 2 consecutive days).
2. Abdominal pain.
3. Lethargy/restlessness.
4. Ascites and/or pleural effusion (clinically and/or confirmed by ultrasonography).
5. Increased hematocrit with decreased platelet count.
• Severe Dengue: Patients positive for NS1 or IgM by MAC ELISA with any of the following features:
1. Severe plasma leakage leading to shock or fluid accumulation with respiratory distress.
2. Severe bleeding.
3. Severe organ involvement:

• Liver: AST or ALT ≥ 1000.
• CNS: Impaired consciousness.
• Heart and other organs.

Patients were categorized into three groups based on the severity: Group 1 (Dengue without warning signs), Group 2 (Dengue with warning signs), and Group 3 (Severe dengue).

Method of Data Collection: The study included clinically suspected cases of dengue confirmed by serological tests for either dengue-specific NS1 antigen assay and/or IgM antibodies detection. A total of 104 patients admitted to VIMSAR, Burla, from November 2017 to October 2019, were selected. Written consent was obtained from the patients or their attendants before enrollment. Detailed clinical histories, physical examinations, and relevant baseline investigations were conducted as per the study proforma. Patients were treated according to WHO guidelines for dengue, which included IV fluids, paracetamol, blood products, and inotropics. Hematological parameters were evaluated using 2 ml blood samples collected in EDTA prefilled vials, examined for hemoglobin count, hematocrit, platelet count, total leukocyte count, and differential leukocyte count. The analysis was performed using the automated analyzer SYSMEX XS 800i (3-part differential). Liver and renal function tests (LFT and RFT) were conducted using the automated biochemical analyzer COBAS C 311.

Ethical Approval: The study was approved by the ethical committee of VIMSAR and was conducted with minimal risk to participants.

Statistical Analysis: Data were entered and analyzed using SPSS version 22 software. All clinical and hematological profile parameters were expressed as mean and standard deviation (SD) values. Appropriate statistical tests, such as ANOVA, post hoc (Bonferroni test), and Kruskal-Wallis tests, were applied to the hematological parameters to compare the groups (Group 1, Group 2, and Group 3). A p-value of less than 0.05 was considered statistically significant.

Age Distribution

Table 1: Age Distribution

Figure.1: Age Distribution

Sex Distribution

Table 2: Gender Distribution

Figure.2: Sex distirbution

Symptomatology

Table 3: Key Symptoms

Figure.3: Symptomatologyin Different Dengue Groups

Dengue Test Results

Table 4: Dengue Positive Results

Figure.4: Dengue Result

Hematological Parameters

Platelet Count

Table 5: Platelet Count

Total Leukocyte Count (TLC)

Table 6: Total Leukocyte Count

Hematocrit

Table 7: Hematocrit

Hemoglobin

Table 8: Hemoglobin

Packed Cell Volume (PCV)

Table 9: Packed Cell Volume

Activated Partial Thromboplastin Time (aPTT)

Table 10: aPTT

These results highlight significant variations in the hematological profile among different groups of dengue patients, suggesting potential biomarkers for disease severity and prognosis. Further detailed analysis and discussion of these findings are warranted to understand the clinical implications and underlying pathophysiological mechanisms.

Hematological Profile in Dengue Fever: The present study underscores the significant role of hematological parameters in the diagnosis and management of dengue fever. Our findings align with previous research, highlighting the characteristic changes in these parameters associated with the disease [9].

Thrombocytopenia emerged as a consistent and crucial hematological abnormality in our cohort, with 46.2% of patients exhibiting platelet counts below the 100,000/cmm threshold. This observation is in concordance with the findings of Singh NP et al., Khan E et al., and Farhan F et al., who reported even higher incidence rates of thrombocytopenia [10]. The statistical significance of this association (p<0.001) reinforces the importance of platelet monitoring in dengue patients.

Leucopenia was another prominent hematological feature, affecting 52% of our study population. This finding is consistent with the observations of Ole Wichmann et al. and Butt et al. [11] The statistically significant association between leucopenia and dengue infection (p<0.001) emphasizes its diagnostic utility.

Hemoconcentration, as evidenced by elevated hematocrit levels, was observed in 9.6% of our patients. This is in line with the findings of Deshwal et al., who reported a similar incidence of raised hematocrit [12]. The significant association between haemoconcentration and dengue infection (p<0.001) underscores its importance in disease severity assessment.

Hemoglobin levels did not show significant variations in our study, a finding that contrasts with some previous reports. This discrepancy might be attributed to differences in study populations, disease severity, or timing of blood sampling [13].

Correlation of Hematological Parameters with Disease Severity: Our study revealed a correlation between certain hematological parameters and the severity of dengue infection. Patients with dengue warning signs (DW) and severe dengue (SD) exhibited higher hematocrit levels compared to those with dengue fever (DF). This finding aligns with the established knowledge that hemoconcentration is a hallmark of dengue shock syndrome [14].

While thrombocytopenia is a common feature of dengue, its correlation with disease severity is complex. Although low platelet counts are often associated with severe dengue, it is essential to consider other clinical factors in assessing disease progression [15].

Limitations and Future Directions: The present study has certain limitations, including its retrospective design and relatively small sample size. Further prospective studies with larger cohorts are warranted to strengthen the findings. Additionally, exploring the correlation between hematological parameters and other clinical variables, such as age, gender, and comorbidities, could provide valuable insights into disease pathogenesis and prognostication. [16]

Our study reaffirms the critical role of hematological parameters in the diagnosis and management of dengue fever. Thrombocytopenia, leucopenia, and hemoconcentration emerged as significant hematological abnormalities associated with the disease. While these parameters can aid in disease severity assessment, a comprehensive clinical evaluation is essential for optimal patient care [17]. Future research should focus on identifying early hematological predictors of severe dengue and exploring the potential of hematological monitoring in guiding therapeutic interventions [18].

The present study highlights the pivotal role of hematological parameters in the diagnosis, management, and prognostication of dengue fever. Our findings underscore the consistent presence of thrombocytopenia, leukopenia, and hemoconcentration among dengue patients, correlating significantly with disease severity[19].

Thrombocytopenia, observed in nearly half of our patient cohort, emerges as a critical marker for dengue, emphasizing the necessity for vigilant platelet monitoring. The substantial prevalence of leukopenia further supports its diagnostic utility, reinforcing the need for regular white blood cell counts in suspected cases. Hemoconcentration, indicative of plasma leakage, is a reliable marker for severe dengue, particularly dengue shock syndrome, underscoring its importance in assessing disease progression [20].

The study also establishes a correlation between specific hematological parameters and disease severity, providing valuable insights into the pathophysiological mechanisms of dengue. Elevated hematocrit levels in patients with warning signs or severe dengue reinforce the role of hemoconcentration as a hallmark of severe disease.

While hemoglobin levels did not show significant variations, this discrepancy may be attributed to differences in study populations and methodologies, highlighting the need for further research in this area. Despite the limitations of a retrospective design and a relatively small sample size, our findings are consistent with existing literature and contribute to a growing body of evidence supporting the utility of hematological monitoring in dengue management.

Future research should focus on prospective studies with larger cohorts to validate these findings and explore the potential of early hematological markers in predicting severe dengue. Additionally, investigating the interplay between hematological parameters and clinical variables such as age, gender, and comorbidities could provide deeper insights into disease pathogenesis and inform targeted therapeutic interventions.

In conclusion, the study reaffirms the critical role of hematological parameters in the comprehensive management of dengue fever. Thrombocytopenia, leukopenia, and hemoconcentration serve as significant markers for disease severity, aiding in early diagnosis and guiding clinical management. Enhanced understanding and monitoring of these parameters can ultimately improve patient outcomes and reduce the burden of this rapidly spreading viral disease.

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