Dengue fever, caused by the dengue virus (DENV) and transmitted primarily by Aedes mosquitoes, represents a significant public health challenge, particularly in tropical and subtropical regions. The global burden of dengue has escalated dramatically over recent decades, with an estimated 390 million infections occurring annually, of which approximately 96 million manifests clinically with varying degrees of severity [1]. The clinical spectrum of dengue ranges from mild febrile illness to severe conditions, including dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which can lead to fatal outcomes.

The pathophysiology of dengue is complex, involving a dynamic interplay of viral, host immune, and vascular factors [2]. One critical aspect of dengue pathogenesis is the alteration in hematological parameters, which not only reflect the disease's systemic impact but also serve as key indicators for clinical diagnosis, management, and prognosis. Hematological abnormalities, such as thrombocytopenia, leukopenia, and hemoconcentration, are common in dengue and can vary significantly depending on the severity of the disease [3].

This study aims to investigate the correlation between dengue severity and hematological profiles in patients admitted to the Department of Internal Medicine at Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Burla. By conducting a detailed analysis of hematological parameters across different clinical categories of dengue—namely, dengue without warning signs, dengue with warning signs, and severe dengue—this research seeks to enhance our understanding of the hematological manifestations associated with varying disease severities [4]. The findings of this study are anticipated to provide valuable insights into the prognostic significance of specific hematological markers and contribute to the development of improved clinical management strategies for dengue patients [5].

The two-year observational study period, spanning from November 2017 to October 2019, encompasses a comprehensive dataset, offering a robust basis for analyzing trends and correlations. By focusing on a cohort of 104 patients confirmed with dengue through serological testing, this study provides a significant contribution to the existing literature on dengue hematology, particularly in the context of an Indian tertiary care setting [6]. The results are expected to have implications for public health policies, particularly in endemic regions, and may inform future research into targeted therapeutic approaches for dengue [7].

Study Design and Setting: This hospital-based observational study was conducted at the Department of Internal Medicine, Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Burla. The study spanned a two-year period, from November 2017 to October 2019, focusing on patients admitted with confirmed dengue infection. The study aimed to analyze the correlation between dengue severity and various hematological parameters.

Study Population and Inclusion Criteria: The study included patients who met the following criteria:

1. Inclusion Criteria:
• Patients aged over 14 years.
• Patients with a positive diagnosis of dengue confirmed by the presence of serum NS1 antigen and/or IgM antibodies using the Enzyme-Linked Immunosorbent Assay (ELISA).
2. Exclusion Criteria:
• Patients co-infected with dengue and malaria, identified through Malaria Parasite-Quantitative Buffy Coat (MP-QBC) or slide test.
• Patients with pre-existing conditions such as chronic kidney disease, chronic liver disease, sickle cell disease, or thalassemia.

Case Definition and Grouping: Patients were categorized into three groups based on the clinical presentation and severity of the disease:

1. Group 1: Dengue without Warning Signs
• Defined by the presence of fever and positive NS1 and/or IgM antibodies, without additional clinical complications such as central nervous system dysfunction, persistent vomiting, abdominal pain, hemorrhage, fluid accumulation, cold clammy skin, hypotension, or features of congestive heart failure (CCF) or respiratory distress.
2. Group 2: Dengue with Warning Signs
• Characterized by positive NS1 and/or IgM antibodies along with one or more of the following symptoms: persistent vomiting, abdominal pain, lethargy/restlessness, ascites and/or pleural effusion (clinically or confirmed by ultrasonography), and increased hematocrit with decreased platelet count.
3. Group 3: Severe Dengue
• Defined by positive NS1 or IgM antibodies accompanied by severe plasma leakage leading to shock or fluid accumulation with respiratory distress, severe bleeding, or severe organ involvement (such as AST or ALT ≥ 1000, impaired consciousness, or significant heart and other organ involvement).

Data Collection: Data were collected from a total of 104 patients who provided written informed consent. Clinical histories and physical examinations were documented using a standardized proforma. Relevant baseline investigations were conducted, including serological testing for dengue-specific NS1 antigen and IgM antibodies.

Hematological Assessments: Blood samples (2 ml) were collected in EDTA prefilled vials for hematological analysis. The following parameters were measured:

• Hemoglobin Count
• Hematocrit
• Platelet Count
• Total Leukocyte Count (TLC)
• Differential Leukocyte Count

These measurements were performed using an automated analyzer (SYSMEX XS 800i, 3-part differential). Additionally, liver and renal function tests (LFT and RFT) were conducted using an automated biochemical analyzer (COBAS C 311).

Ethical Considerations: The study was approved by the Institutional Ethics Committee of VIMSAR. All procedures were conducted in accordance with the ethical standards set forth by the Helsinki Declaration, ensuring minimal risk to participants.

Statistical Analysis: Data were entered and analyzed using SPSS software (version 22). Descriptive statistics were employed to summarize the clinical and hematological parameters. Continuous variables were expressed as mean ± standard deviation (SD). Comparative analyses were conducted using ANOVA, post hoc (Bonferroni test), and Kruskal-Wallis tests to determine the statistical significance of differences between the groups (Group 1, Group 2, and Group 3). A p-value of less than 0.05 was considered statistically significant, indicating meaningful differences in hematological profiles across different severities of dengue.

Age Distribution: The study included 104 dengue patients categorized into three groups based on disease severity. The age distribution of the patients is detailed in Table 1. The mean age of patients was 28.37 ± 10.72 years, with no significant difference observed among the groups (p = 0.157).

Figure 1: Age Distribution

Sex Distribution: The sex distribution among the groups showed a predominance of male patients (84.6%). The distribution across groups was as follows: Group 1 had 83% males, Group 2 had 86.7% males, and Group 3 had 85.7% males. There was no statistically significant difference in the gender distribution among the groups (p = 0.976).

Figure 2: Sex Distribution

Symptomatology: The symptom profile revealed that fever was universally present across all groups (100%). Other common symptoms included arthralgia/myalgia (94.2%), nausea/vomiting (53.8%), and headache (79.8%). Notably, symptoms such as rash (43.3%), abdominal pain (57.7%), bleeding (21.2%), pedal edema (7.7%), pleural effusion (2.9%), and ascites (14.4%) showed significant variations across groups, with p-values indicating statistical significance for rash, abdominal pain, bleeding, pedal edema, pleural effusion, and ascites.

Figure 3: Symptomatology in Different Dengue Groups

Dengue Test Results: The serological testing showed that NS1 antigen was positive in 33.6% of cases, while IgM antibodies were positive in 66.3% of cases. The distribution among the groups is summarized in Table 4.

Figure 4: Dengue Test Results

Hematological Parameters: The analysis of hematological parameters revealed significant differences across the three groups:

1. Platelet Count:

• The mean platelet count was lowest in Group 3 (61.8 x10³/µL) and highest in Group 1 (118.9 x10³/µL) with a significant p-value of 0.001.

2. Total Leukocyte Count (TLC):

• TLC was also lowest in Group 3 (3.51 x10³/µL) and highest in Group 1 (5.49 x10³/µL), with a significant p-value of 0.016.

3. Hematocrit:

• Hematocrit levels were significantly elevated in Group 3 (52.7%) compared to Group 1 (40.7%), with a p-value of 0.0001.

4. Hemoglobin:

• Mean hemoglobin levels did not show a statistically significant difference across the groups (p = 0.213).

5. Packed Cell Volume (PCV):

• PCV was significantly higher in Group 3 (52.7%) compared to Group 1 (40.7%), with a p-value of 0.0001.

6. Activated Partial Thromboplastin Time (aPTT):

• The mean aPTT was highest in Group 3 (37.8 seconds) and lowest in Group 1 (34.1 seconds), with a p-value of 0.015.

These results highlight significant variations in hematological profiles across the different severity groups of dengue, providing critical insights into the potential biomarkers for disease severity and prognosis. Further detailed analysis and discussion of these findings will help elucidate the clinical implications and underlying pathophysiological mechanisms in dengue patients.

This study explores the impact of dengue severity on hematological profiles through a comprehensive two-year observational study conducted at the Department of Internal Medicine, Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Burla. By examining 104 confirmed dengue patients across different disease severities, we aim to deepen our understanding of how dengue severity correlates with various hematological parameters and its implications for clinical management and prognosis [8].

Age and Sex Distribution: The study population exhibited a mean age of 28.37 years, with no significant difference among the severity groups (p = 0.157). This finding suggests that dengue fever affects individuals across a broad age range, and age may not be a significant factor in determining disease severity [9]. The male predominance observed in this study (84.6%) aligns with previous studies indicating a higher incidence of dengue in males, though the differences across severity groups were not statistically significant (p = 0.976). This gender distribution reflects broader epidemiological trends and suggests that male patients may be more frequently affected, though this does not directly correlate with disease severity in our cohort [10].

Symptomatology: The symptom profile revealed that fever was universally present among all patients, consistent with the hallmark presentation of dengue. Arthralgia/myalgia, nausea/vomiting, and headache were also commonly reported. Notably, significant variations in symptoms such as rash, abdominal pain, bleeding, pedal edema, pleural effusion, and ascites were observed among the severity groups. These variations underscore the complexity of dengue's clinical presentation and its progression [11]. For instance, the presence of abdominal pain and bleeding was significantly associated with higher severity, as indicated by the low p-values (0.0001 for abdominal pain and 0.0001 for bleeding). These findings align with established clinical observations where severe dengue manifestations often include abdominal pain and bleeding complications, indicative of more advanced disease stages [12].

Dengue Test Results: The serological testing data revealed that NS1 antigen positivity was observed in 33.6% of cases, while IgM antibodies were positive in 66.3%. The distribution of NS1 and IgM positivity among the severity groups was relatively consistent, though a slight increase in NS1 positivity was noted in Group 3 [13]. This trend is consistent with the understanding that NS1 antigen levels may fluctuate with disease severity, reflecting ongoing viral replication and systemic involvement.

Hematological Parameters

Platelet Count: Platelet count significantly decreased from Group 1 to Group 3, with the lowest count observed in the most severe cases (Group 3). The mean platelet count in Group 3 was significantly lower than in Group 1 (61.8 vs. 118.9 x10³/µL, p = 0.001). Thrombocytopenia is a well-documented feature of dengue and is particularly pronounced in severe cases [14]. This trend aligns with the pathophysiological understanding that severe dengue is associated with more pronounced platelet reduction due to increased peripheral destruction and consumption [15].

1. Total Leukocyte Count (TLC): TLC also demonstrated a significant decline with increasing disease severity (Group 1: 5.49 x10³/µL; Group 3: 3.51 x10³/µL, p = 0.016). The reduction in TLC is indicative of leukopenia, which is common in dengue and can exacerbate as the disease progresses. This finding supports the role of leukopenia as a marker of dengue severity [16].
2. Hematocrit: Hematocrit levels increased with disease severity, with the highest levels observed in Group 3 (52.7%). This increase is statistically significant (p = 0.0001) and reflects hemoconcentration, a key indicator of plasma leakage in severe dengue. Hemoconcentration results from fluid loss into the extravascular space, a hallmark of severe dengue and dengue hemorrhagic fever (DHF) [17].
3. Hemoglobin and Packed Cell Volume (PCV): Hemoglobin levels did not show significant variation across the groups, which may suggest that hemoglobin levels are less sensitive to changes in dengue severity compared to other parameters. However, PCV levels mirrored the trend in hematocrit, with significantly higher values in Group 3 (52.7%) compared to Group 1 (40.7%, p = 0.0001). This further supports the role of PCV as a critical parameter in assessing dengue severity [18].
4. Activated Partial Thromboplastin Time (aPTT): The mean aPTT was significantly prolonged in Group 3 (37.8 seconds) compared to Group 1 (34.1 seconds, p = 0.015). Prolonged aPTT can be associated with disseminated intravascular coagulation (DIC) and coagulation abnormalities in severe dengue, reflecting the disease's systemic impact on clotting mechanisms.

This study highlights significant variations in hematological profiles across different severity levels of dengue. Key findings include pronounced thrombocytopenia, leukopenia, and elevated hematocrit and PCV in severe dengue cases, reinforcing the importance of these hematological markers in disease assessment and management [19]. The results provide valuable insights into the pathophysiological mechanisms underlying dengue severity and offer a basis for refining diagnostic and therapeutic approaches in clinical settings. Further research is needed to explore the underlying mechanisms driving these hematological changes and to develop targeted interventions for managing severe dengue cases effectively.

This two-year observational study at Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Burla, provides significant insights into how dengue severity affects hematological profiles. By analyzing 104 patients with confirmed dengue across three distinct clinical categories—dengue without warning signs, dengue with warning signs, and severe dengue—we have elucidated key hematological variations that correlate with disease severity [20].

The study revealed a notable decline in platelet count and total leukocyte count (TLC) with increasing dengue severity, highlighting pronounced thrombocytopenia and leukopenia as critical markers of severe disease. Hematocrit and packed cell volume (PCV) levels, conversely, showed a significant increase in severe cases, reflecting the underlying pathophysiological process of plasma leakage and hemoconcentration. These findings underscore the importance of monitoring these hematological parameters for assessing disease progression and guiding clinical management.

The mean age of the study population did not differ significantly among severity groups, suggesting that age is not a decisive factor in dengue severity. However, the predominance of male patients aligns with broader epidemiological trends, though this demographic factor did not show a significant impact on disease severity within our cohort.

Symptom analysis further corroborated the association of certain clinical features—such as abdominal pain, bleeding, pedal edema, pleural effusion, and ascites—with more severe dengue cases. These symptoms, along with significant hematological deviations, offer valuable insights into the disease’s clinical spectrum and progression.

Serological testing showed consistent positivity for NS1 antigen and IgM antibodies across severity groups, with a slight increase in NS1 positivity in severe cases. This observation aligns with the role of NS1 antigen as an indicator of viral replication and severity.

Overall, this study emphasizes the critical role of hematological parameters in the diagnosis and management of dengue fever. The significant variations in platelet count, TLC, hematocrit, and PCV among different severity groups provide a robust basis for refining diagnostic criteria and therapeutic strategies. These findings contribute to a deeper understanding of dengue's impact on the hematological system and highlight the need for ongoing research to develop targeted interventions for effective disease management.

Future studies should aim to explore the mechanistic underpinnings of these hematological changes and investigate potential therapeutic approaches tailored to the severity of dengue. This research not only enhances clinical practices but also informs public health strategies, particularly in endemic regions, to mitigate the impact of dengue fever on affected populations.

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