Abstract
INTRODUCTION: Dengue fever remains a public health challenge in Nepal, with hematological abnormalities like leukopenia and thrombocytopenia often observed. However, their prevalence and clinical significance outside the Kathmandu Valley remain poorly characterized. This study examines these markers in Koshi Province, a region prone to recurrent outbreaks but with limited data, to enhance regional understanding and early severity detection. METHODS: A cross-sectional study was conducted across four tertiary hospitals in Sunsari district, Koshi province of Nepal during the 2022 dengue outbreak. A convenience sample of 325 laboratory-confirmed dengue patients (NS1 antigen/IgM/IgG positivity) was enrolled. Data on demographics, clinical features, leukocytes count, and platelet counts were collected using Case Report Form (CRF). Hematological parameters (leukocyte count < 4,000 cells/mm³; and platelet count < 150,000 cells/mm³) were analyzed alongside clinical severity (WHO 2009 classification: DWWS, DWS, SD). Chi-square tests, adjusted residuals and logistic regression (adjusted for age and diabetes) were used to assess associations between these hematological markers and dengue severity. Additional analyses were performed to examine associations of leukopenia and thrombocytopenia with demographic characteristics (e.g., age, sex) and clinical symptoms (e.g., joint pain, rash, retro-orbital pain, nausea). RESULTS: Leukopenia was observed in 21.5% of patients, while thrombocytopenia occurred in 62.1%. Leukopenia showed a significant association with DWS (χ²=5.481, p = 0.019; Cramér's V = 0.13), with adjusted residuals highlighting its stronger link to DWS (AR = 3.40). Thrombocytopenia, though prevalent, was more common in milder cases (DWWS). Logistic regression confirmed leukopenia's association with severity (OR = 0.9999, p = 0.011), while thrombocytopenia paradoxically correlated with slightly increased severity odds (OR = 1.000005, p = 0.023). Leukopenia was significantly associated with symptoms such as joint pain, nausea, and rash, while thrombocytopenia was linked to retro-orbital pain and abdominal discomfort. No significant associations were observed between these hematological abnormalities and sex or age group. CONCLUSION: This study highlights leukopenia as an early marker of dengue severity in Koshi province, while challenging thrombocytopenia's assumed role in disease progression. Despite limitations from convenience sampling and single-timepoint data, this study provides actionable insights for risk stratification in regional dengue management. Future longitudinal studies are needed to validate these associations and refine multivariable risk models. CLINICAL TRIAL REGISTRATION DETAILS: Clinical trial number: not applicable.