Abstract
Dengue fever (DF) is a viral infection transmitted between humans by Aedes mosquitoes. To identify DF and evaluate severity, serological tests and clinical parameters are commonly used, but these may not be available in small local hospitals or subjective. The study aimed to identify the correlation of changes in complete blood count, including white blood cells (WBC), red blood cells (RBC), and platelet with severity of DF. This is a cross-sectional study, conducted at Bach Mai Hospital between October 2023 and February 2024. Data was imported to Excel then transferred to SPSS for analysis using the ANOVA or paired t-test. The study included 182 patients with a mean age of 41.1 ± 20.77 years (age range: 3–95). Patients with severe DF had significantly higher WBC counts and the neutrophil percentage compared to those with mild DF and DF with warning signs (P < .05). Patients with severe DF had a significantly lower lymphocyte percentage and the RBC count compared to those with mild DF and DF with warning signs (P < .05). Hematocrit values were similar across all groups (P > .05) and platelet counts were relatively similar across the groups (P > .05). Patients with severe DF had significantly higher WBC and neutrophil percentages, as well as lower lymphocyte and RBC counts, compared to those with non-severe DF. Significant changes in these parameters can help identify patients at risk of severe DF, allowing for timely intervention in small local hospitals.
Keywords: Aedes mosquitoes, complete blood count, dengue fever, lymphocytes, neutrophil, predictors, red blood cells, severity, white blood cells
1. Introduction
Dengue fever (DF) is a viral infection transmitted between humans by Aedes mosquitoes.[1] Currently, there is no approved vaccine or specific treatment, and despite significant efforts to control the epidemic, its rapid emergence and global spread have not been prevented.[2,3] The severity of dengue infection can vary widely, ranging from mild illness to dengue shock syndrome and even death. Patients usually present with a sudden onset of fever and nonspecific symptoms, making it difficult to distinguish from other infectious diseases.
Currently, serological tests are used to confirm dengue infection, including detection of the dengue NS1 antigen, which has a sensitivity of 76% and specificity of 98%, and the dengue IgM antibody through the ELISA method, which offers 90% sensitivity and 93% specificity.[4,5] However, levels of IgM or IgG can be only reliably detected in 3 to 4 days after symptoms begin, leading to potential false-negative results. In underdeveloped countries or smaller local hospitals, these serological tests may not be readily accessible, making clinical information from patient history, physical examination, and basic laboratory tests essential for diagnosis.
Several clinical parameters have been proposed as predictors, such as abdominal pain, vomiting, nausea, hepatomegaly, fluid accumulation, bleeding, respiratory distress, altered mental status, and shock. However, these parameters can be subjective as they depend on clinical experience.[4,6]
The Complete blood count (CBC), including hemoglobin (Hb), hematocrit (Hct), white blood cells (WBC) count, differential percentages of WBCs, and platelet count, change daily in dengue-infected patients.[4] There is limited evidence identifying these daily changes to distinguish dengue from other causes of acute febrile illness without specific localizing signs. The study aimed to identify the correlation of changes in WBC (total count, percentages of neutrophil or lymphocytes), red blood cells (total count, Hct), and platelet with severity of DF.
2. Methods
The study protocol was approved by the Bach Mai Hospital Institute Board Review (IRB No. 2460/BM – HDDD) and ethics committee. Informed consent was obtained from all individual participants included in the study. This is a cross-sectional study, conducted at Bach Mai Hospital between October 2023 and February 2024. The inclusion criteria consisted of patients presenting with an acute febrile illness lasting <7 days, with no identifiable source of infection. Patients are clinically diagnosed with DF when they meet at least 2 clinical criteria and 2 laboratory criteria.
Clinical criteria:
Acute fever lasting 2 to 7 days.
Hemorrhage: Subcutaneous bleeding, mucosal bleeding, or positive tourniquet test.
Enlarged liver.
Laboratory criteria
Platelet count below 100,000/mm³.
Hematocrit increase > 20% compared to normal.
Acute circulatory failure: Low blood pressure (systolic BP < 90 mm Hg) or narrow pulse pressure (systolic BP - diastolic BP ≤ 20 mm Hg).
Positive dengue virus antibody tests: IgG and IgM (+).
Exclusive criteria included patients who did not meet the above criteria. Patients were with concurrent infectious, hematologic conditions (anemia, malignant blood diseases, thrombocytopenic bleeding disorders, or hemophilia), or other internal diseases.
The CBC information was imported to Microsoft Excel. The data was presented as mean ± standard deviation and analyzed by ANOVA, following Tukey tests using IBM SPSS version 25, or paired t-tests (IBM Corp., Armonk). A P-value of <0.05 was considered statistically significant.
3. Results
The study included 182 patients with a mean age of 41.1 ± 20.77 years (age range: 3–95). Among them, 138 patients had mild DF (75.8%), 32 patients had DF with warning signs (17.6%), and 12 patients had severe DF (6.6%). Patients with severe DF had a significantly higher mean age compared to those with mild DF (P < .05), while there was no significant difference in mean age between the group with warning signs and the other 2 groups. The mean age of patients with mild DF was 38.8 ± 19.3, while the mean age for those with warning signs was 42.3 ± 24.4, and the group with severe DF had the highest mean age of 64.5 ± 11.8 (Table 1).
Table 1.
Association between age and severity of DF (n = 182).
| Mild DF | DF with warning signs | Severe DF | |
|---|---|---|---|
| No. of patients | 138 (75.8%) | 32 (17.6%) | 12 (6.6%) |
| Mean age ± SD | 38.8 ± 19.3 | 42.3 ± 24.4 | 64.5 ± 11.8*,† |
DF = dengue fever, SD = standard deviation.
P < .05 vs mild DF.
P < .05 vs DF with warning signs.
Patients with severe DF had significantly higher WBC counts compared to those with mild DF and DF with warning signs (11.1 ± 6.1, 5.4 ± 2.7, 5.9 ± 2.3, respectively, P < .05). The neutrophil percentage was significantly higher in patients with severe DF compared to those with mild DF and DF with warning signs (64.3 ± 18.9, 40.9 ± 15.1, 41.0 ± 16.1, respectively, P < .05). Patients with severe DF had a significantly lower lymphocyte percentage compared to those with mild DF and DF with warning signs (21.1 ± 16.2, 38.4 ± 13.1, 35.7 ± 12.2, respectively, P < .05). The RBC count was significantly lower in patients with severe DF compared to those with mild DF and DF with warning signs (3.9 ± 0.7, 4.8 ± 0.6, 4.5 ± 1.1, respectively, P < .05). Hematocrit values were similar across all groups (0.4 ± 0.1, P > .05) and platelet counts were relatively similar across the groups (P > .05). Patients with mild DF had a platelet count of 60.9 ± 57.4, those with DF with warning signs having 51.5 ± 50.5, and those with severe DF having 58.1 ± 33.3 (Table 2).
Table 2.
Association of hematological parameters and severity of DF.
| Mild DF | DF with warning signs | Severe DF | |
|---|---|---|---|
| WBC | 5.4 ± 2.7 | 5.9 ± 2.3 | 11.1 ± 6.1*,† |
| Neu% | 40.9 ± 15.1 | 41.0 ± 16.1 | 64.3 ± 18.9*,† |
| Lymp% | 38.4 ± 13.1 | 35.7 ± 12.2 | 21.1 ± 16.2*,† |
| RBC | 4.8 ± 0.6 | 4.5 ± 1.1 | 3.9 ± 0.7*,† |
| HCT | 0.4 ± 0.1 | 0.4 ± 0.1 | 0.4 ± 0.1 |
| PLT | 60.9 ± 57.4 | 51.5 ± 50.5 | 58.1 ± 33.3 |
DF = dengue fever, Lymp% = percentage of lymphocytes, Neu% = percentage of neutrophils, SD = standard deviation, WBC = white blood cells.
P < .05 vs mild DF.
P < .05 vs DF with warning signs.
To ensure balanced group sizes for comparison, the number of patients in each category, “mild DF,” “DF with warning signs,” and “severe DF,” was set to 12, based on the available number of severe DF cases. Significant differences (P < .05) are noted between the “mild” and “severe” categories in WBC count, neutrophil percentage, lymphocyte percentage, and RBC count. Platelet counts and hematocrit values do not show significant differences between the groups (P > .05). Early identification of severe dengue can be supported by monitoring WBC, neutrophils, lymphocytes, and RBC values. Neutrophil dominance and lymphopenia could serve as early red flags for worsening disease, especially in settings lacking serological diagnostics. Platelet and hematocrit values, though traditionally used in DF management, may be less reliable indicators of severity at a single time point (Table 3).
Table 3.
Complete blood count parameters in equal-sized dengue fever groups (n = 12).
| Parameter | Mild DF | DF with warning Signs | Severe DF | P-value (mild vs severe) |
|---|---|---|---|---|
| WBC (×109/L) | 5.4 ± 2.7 | 5.9 ± 2.3 | 11.1 ± 6.1 | <.05 |
| Neutrophil % | 40.9 ± 15.1 | 41.0 ± 16.1 | 64.3 ± 18.9 | <.05 |
| Lymphocyte % | 38.4 ± 13.1 | 35.7 ± 12.2 | 21.1 ± 16.2 | <.05 |
| RBC (×1012/L) | 4.8 ± 0.6 | 4.5 ± 1.1 | 3.9 ± 0.7 | <.05 |
| Platelet Count (×109/L) | 60.9 ± 57.4 | 51.5 ± 50.5 | 58.1 ± 33.3 | >.05 |
| Hematocrit (%) | 40 ± 0.1 | 40 ± 0.1 | 40 ± 0.1 | >.05 |
Data was presented as mean ± standard deviation.
DF = dengue fever.
4. Discussion
Globally, approximately 390 million cases of dengue virus infection are reported annually, with 96 million cases presenting clinically with severe symptoms, resulting in 21,000 deaths. More than 3.9 billion people are at risk of dengue infection. Although over 128 countries are at risk of infection, 70% of the actual burden occurs in Asia and South America.[7–11]
Patients with DF usually present with an acute febrile illness lacking localized signs or symptoms, making it difficult to distinguish from other infections, including tropical diseases like rickettsial infections, leptospirosis, malaria, or various viral illnesses. Common clinical presentations of DF include fever, headache, loss of appetite, nausea, bleeding tendencies, muscle pain, abdominal pain, sore throat, and diarrhea.[12–14] These symptoms are nonspecific and can also occur with other infections. Serological tests (NS1, IgM, IgM) are employed to confirm dengue infection; however, these laboratory tests may be inaccessible in some rural areas, local hospitals, or undeveloped countries. Our study identified significant differences in CBC parameters that aid in distinguishing dengue infection from these other causes.
Our study excluded patients with other conditions such as hematologic disorders, cardiovascular diseases, lung-related diseases, diabetes, or hypertension. This was to avoid the impact of preexisting conditions on the assessment of the relationship between age and DF severity. The study found a mean age of 41.1 years, and older patients were more likely to develop severe DF compared to younger patients. Many studies have focused on overall infection risk according to age groups. Nguyen-Tien et al reported older individuals had a lower risk of dengue infection compared to younger individuals. Specifically, those aged 31 to 45, 46 to 60, and over 60 years had a 57%, 62%, and 95% lower risk, respectively, of contracting DF compared to patients aged 16 to 30.[15] Another study showed individuals aged 15 to 34 years have been identified as the most frequently affected age group during dengue outbreaks in Vietnam and Singapore.[16,17]
Our study supported that although older population has lower infection risk, they likely to develop severity than the younger. This could be because their immune system typically becomes less robust and less effective at responding to infections. This reduced immune response can lead to a higher risk of severe disease. Another potential reason could be that older patients might experience delays in recognizing symptoms or seeking medical attention. Therefore, it is suggested that health information, education and communication programs on dengue prevention and control should be provided to all age groups but focused on the early about severity developing.
Many studies have identified parameters to support initial diagnosis and assess severity of DF. Oehadian et al reported detection of atypical lymphocytes, high-fluorescent lymphocyte counts, immature granulocytes, and immature platelets by Sysmex XE-5000 hematology analyzers could be useful for initial diagnosis.[18] Prolonged activated partial thromboplastin time, prothrombin time, thrombin time, along with elevated liver enzyme levels, may serve as helpful indicators in the diagnosis of dengue infection.[19] To help predict the severity of dengue infection, factors such as monocytosis, prolonged duration of thrombocytopenia, elevated percentages of atypical lymphocytes, and increased serum levels of lactate and lactate dehydrogenase were utilized.[20]
These parameters may only be accessible at modern hospitals; therefore, evaluating the CBC, a widely available laboratory test, proved effective in assessing DF severity. Our study demonstrated that patients with severe DF had significantly higher WBC and neutrophil percentages, as well as lower lymphocyte and RBC counts, compared to those with mild DF and those with warning signs. In hospitals where advanced diagnostic tools may not be available, it is recommended that clinicians closely monitor WBC, neutrophil, lymphocyte, and RBC counts in patients suspected of having DF. Significant changes in these parameters can help identify patients at risk of severe DF, allowing for timely intervention. Doctors should receive additional training on interpreting CBC results in the context of DF. This will enhance their ability to detect early signs of disease progression and make informed decisions about patient care.
The study had several limitations. Although we assessed all available medical records, the sample size was relatively small. The enrollment process was based on diagnosis and a review of fever history that met the inclusion criteria, which may have introduced selection bias and potentially impacted the overall quality of the study. To validate our findings, prospective or case-control studies on this topic are recommended across multiple centers and over a longer period to validate the findings.
5. Conclusion
Patients with severe DF had significantly higher WBC and neutrophil percentages, as well as lower lymphocyte and RBC counts, compared to those with mild DF and those with warning signs. These findings are consistent with several previous studies. For instance, Thanachartwet et al also reported that leukocytosis, neutrophilia, and lymphopenia were associated with severe dengue outcomes.[20] Similarly, Oehadian et al found that parameters like immature granulocytes and atypical lymphocytes were helpful in early identification of severe cases.[18]
While many previous studies have focused on more advanced biomarkers or equipment-dependent parameters, our results emphasize the clinical utility of basic CBC components – which are widely accessible even in resource-limited settings. Unlike hematocrit and platelet counts, which did not show statistically significant differences across groups in our study, the consistent shifts in WBC, neutrophils, lymphocytes, and RBCs may provide more reliable, earlier clues to severity. These similarities across studies strengthen the argument that CBC parameters, especially WBC differentials, are useful tools in severity assessment.
Therefore, significant changes in these parameters can help identify patients at risk of severe DF, allowing for timely intervention in small local hospitals. Clinicians should be encouraged to monitor and interpret these markers proactively, especially in settings lacking serological tests or advanced diagnostics.
Author contributions
Conceptualization: Duc Nhu Dang, Hoang Thien Minh Tran.
Data curation: Duc Nhu Dang, Thi Vinh An Do, Tuan Tung Nguyen, Hoang Thien Minh Tran, Manh Quan Ngo, Ngoc Nghia Nguyen, Huynh Phuong Anh Nguyen, Thi Ly Tran, Trong Khoa Nguyen, Huy Luong Duong, Lam Toi Phung, Thi Thu Ha Luong, Trong Thanh Vo, Vuong The Vinh Tran, Hoang Hiep Phan, Quoc Thang Tran.
Formal analysis: Manh Quan Ngo, Ngoc Nghia Nguyen, Huynh Phuong Anh Nguyen, Thi Ly Tran, Trong Khoa Nguyen, Huy Luong Duong, Lam Toi Phung, Thi Thu Ha Luong, Trong Thanh Vo, Vuong The Vinh Tran, Hoang Hiep Phan, Quoc Thang Tran.
Funding acquisition: Manh Quan Ngo.
Investigation: Duc Nhu Dang, Manh Quan Ngo.
Methodology: Duc Nhu Dang, Thi Vinh An Do, Hoang Thien Minh Tran, Manh Quan Ngo, Vuong The Vinh Tran.
Project administration: Hoang Thien Minh Tran, Manh Quan Ngo, Vuong The Vinh Tran.
Resources: Vuong The Vinh Tran.
Visualization: Tuan Tung Nguyen, Vuong The Vinh Tran.
Writing – original draft: Duc Nhu Dang, Thi Vinh An Do, Tuan Tung Nguyen, Hoang Thien Minh Tran, Manh Quan Ngo, Ngoc Nghia Nguyen, Huynh Phuong Anh Nguyen, Thi Ly Tran, Trong Khoa Nguyen, Huy Luong Duong, Lam Toi Phung, Thi Thu Ha Luong, Trong Thanh Vo, Vuong The Vinh Tran, Hoang Hiep Phan, Quoc Thang Tran.
Writing – review & editing: Duc Nhu Dang, Thi Vinh An Do, Tuan Tung Nguyen, Hoang Thien Minh Tran, Manh Quan Ngo, Ngoc Nghia Nguyen, Huynh Phuong Anh Nguyen, Thi Ly Tran, Trong Khoa Nguyen, Huy Luong Duong, Lam Toi Phung, Thi Thu Ha Luong, Trong Thanh Vo, Vuong The Vinh Tran, Hoang Hiep Phan, Quoc Thang Tran.
Abbreviations:
- CBC
- Complete blood count
- DF
- Dengue fever
- Hb
- Hemoglobin
- Hct
- Hematocrit
- RBC
- Red blood cells
- WBC
- White blood cells
The study protocol was approved by the Bach Mai Hospital Institute Board Review (IRB No. 2460/BM – HDDD) and ethics committee.
The authors have no funding and conflicts of interest to disclose.
Corresponding authors take full responsibility for the data, analyses and interpretation of the data, and for providing accurate data availability policies.
How to cite this article: Dang DN, Do TVA, Nguyen TT, Tran HTM, Ngo MQ, Nguyen NN, Nguyen HPA, Tran TL, Nguyen TK, Duong HL, Phung LT, Luong TTH, Vo TT, Tran VTV, Phan HH, Tran QT. Alternative markers in complete blood count as predictors of dengue fever severity. Medicine 2025;104:31(e43564).
All authors have read and agreed to the published version of the manuscript.
Contributor Information
Duc Nhu Dang, Email: dangnhu258@yahoo.com.
Thi Vinh An Do, Email: vinhanbm@gmail.com.
Tuan Tung Nguyen, Email: ntkhoa.moh@gmail.com.
Hoang Thien Minh Tran, Email: thang.tranquoc@phenikaa-uni.edu.vn.
Manh Quan Ngo, Email: quanbts@gmail.com.
Ngoc Nghia Nguyen, Email: ntkhoa.moh@gmail.com.
Huynh Phuong Anh Nguyen, Email: ntkhoa.moh@gmail.com.
Thi Ly Tran, Email: thang.tranquoc@phenikaa-uni.edu.vn.
Trong Khoa Nguyen, Email: ntkhoa.moh@gmail.com.
Huy Luong Duong, Email: dr.luong.vn@gmail.com.
Lam Toi Phung, Email: Toiphunglam@gmail.com.
Thi Thu Ha Luong, Email: ha.luongthu@imp.org.vn.
Trong Thanh Vo, Email: nihbt.nlh2010@gmail.com.
Vuong The Vinh Tran, Email: thang.tranquoc@phenikaa-uni.edu.vn.
Hoang Hiep Phan, Email: hoanghiepbvnt@gmail.com.
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