Hematological Parameters in Dengue: The Serological Angle A Study

Anagha A Joshi, Divyashree BN, Gayathri BR

Anagha A Joshi, Department of Pathology, Kempegowda Institute of Medical Sciences, Research Centre, Bengaluru, Karnataka, India
Divyashree BN, Department of Pathology, Kempegowda Institute of Medical Sciences, Research Centre, Bengaluru, Karnataka, India
Gayathri BR, Department of Pathology, Kempegowda Institute of Medical Sciences, Research Centre, Bengaluru, Karnataka, India

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http: //creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Divyashree BN, Department of Pathology, Kempegowda Institute of Medical Sciences, Research Centre, Bengaluru, Karnataka, India.
Email: divyashree234@gmail.com
Telephone: +9110213154

Received: December 18, 2017
Revised: April 18, 2018
Accepted: April 23, 2018
Published online: May 3, 2018


AIM: : Dengue occurs as epidemics in India. As there is no specific antiviral therapy, early diagnosis in resource poor settings helps reduce mortality. Our study is to analyse the utility of hematology parameters in association with serology patterns in dengue.

MATERIALS AND METHODS: A total of 132 serologically proven dengue cases over a month period in November 2016 along with relevant hematological data (obtained by automated hematology analyser and peripheral smears) were analyzed.

RESULTS: The age range was 5months to 65years with male preponderance.Serology patterns showed NS1 antigen positivity in 29% and IgG positivity in 25%. Rise in hematocrit was noted in 38% of NS1 with antibody as against 28% of NS1 only cases, indicating it was a later event. Leucopenia was prominent (87%) in NS1 (alone and NS1 with antibody) indicating it was an early marker of dengue. Leucocytosis (83%) and neutrophilia (50%) were noted in antibody patterns indicating that they could be late events (parameters). Thrombocytopenia was noted in 43% of antibody pattern as against 21% of NS1 pattern, indicating it was a late event.

CONCLUSION: In resource limited rural setups in India, haematological parameters may have utility as early markers of dengue and in association with serology aid in early diagnosis and management.

Key words: Dengue; NS1 antigen; Antibody; Blood counts

© 2017 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Joshi AA, Divyashree BN, Gayathri BR. Hematological Parameters in Dengue: The Serological Angle A Study. International Journal of Hematology Research 2018; 4(1): 180-184 Available from: URL: http://www.ghrnet.org/index.php/ijhr/article/view/2232


Dengue, an arboviral infection (DENV 1-4) transmitted by Aedes mosquito manifests as an acute febrile illness and is endemic in India. It affects 100 millions worldwide with 2,50,000 cases of dengue haemorrhagic fever and 24,000 deaths annually[1,2]. In India, epidemics are more frequent, straining the limited resources of the public health system[3].

The clinical manifestations of Dengue include fever, headache, muscle & joint pain, nausea, vomiting and rash. In the early phase, it has to be differentiated from other febrile illnesses like malaria, typhoid, leptospirosis etc[4]. Dengue has been classified as Non Severe Dengue with and without warning signs and Severe Dengue (WHO 2009)[5].While Dengue is a self limiting condition, severe forms if not detected early and treated properly are lethal in 5-10% of cases[6].

Dengue is diagnosed by viral isolation, detection of viral genomic sequence by reverse transcription polymerase chain reaction (RT-PCR) (not possible in peripheral areas with limited resources in health care system) and detection of NS1 antigen with corresponding IgM, IgG antibodies by Enzyme immunoassay & Immunochromatographic test (EIA&ICT)[1,2,7,8]. The latter are simple, rapid and easy diagnostic tests which are excellent tools for potentially fatal and epidemic prone infections[8,9].

Apart from these, platelet count is the only lab test available in peripheral areas which supplements a diagnosis of Dengue haemorrhagic fever (DHF)/ Dengue shock syndrome (DSS)[2,8,9]. It has been observed that a drop in platelet counts with a rise in haematocrit occurs after the 3rd day of illness. The platelet counts serve as a predictive and recovery parameter of DHF/DSS[10].

However, it has been noted that the other hematology parameters like total white cell count, atypical lymphocyte count and haematocrit too aid in diagnosis and prognosis in dengue[4,10,11]. While a few studies emphasised the utility of platelet counts in association with serology[1,2]. Occasional studies only have evaluated the utility of other hematology parameters in association with serology[12].

Our study focusses on the utility of these hematology parameters including platelet counts, but where platelet count is not an early indicator of dengue[1], the total leucocyte counts- leucopenia & lymphocytosis are earlier and prominent events in dengue[13] along with haematocrit in resource limited rural set ups[14].

The aim of the study is to: (1) Assess utility of hematology parameters (total leucocyte count, differential counts, platelet counts & haematocrit) in association with serology patterns in dengue; (2) Analyse serology patterns in dengue.


This is a prospective study done on 132 patients with positive dengue serology in hematology department of Kempegowda Institute of Medical Sciences Hospital & Research Centre, Bangalore over a one month period in Nov 2016.

The inclusion criteria were: all patients with serological confirmation of dengue (NS1, IgM, IgG antibody positivity by Rapid card method-Standard diagnostics Biolene Alera) with associated tests haematocrit, leucocyte counts, thrombocytopenia(< 1.5 lakhs/cumm) were included in the study (as low platelet counts were significant in dengue).

The exclusion criteria were: (1) Patients with dengue seropositivity with normal & increased platelet counts; (2) Patients with concomitant infections like malaria, typhoid etc along with dengue.

The haematological data (obtained from automated hematology analyser- Sysmex 1800i) was tabulated for analysis.

The peripheral smears (made for cross verification of platelet as per hospital protocol) was screened for estimation of platelets & differential counts.

Results of dengue tests were obtained from microbiology department.

Ethical committee clearance

The study involves analysis of available data for which informed consent has been obtained at the clinical side for testing.

The study maintains anonymity of patient identity by recording only age & gender against the unique hospital identification number along with relevant data.

The study was approved by ethical committee of hospital.


A total of 132 dengue serology positive cases were analysed. The age range was between 5 months to 65 years with most cases in the 12-25 years group. The average age was 32 years. There was a slight male predominance with male: female ratio of 1.2:1 (Table 1).

Table 1 Age & gender distribution of platelets.
CasesAge groupGender Total
≤ 12 years>12 yearsMale Female

Lab Parameters

(1) Serology Test. (1) The serology pattern showed predominance of NS1 antigen followed by IgG. (2) The age & gender distribution of serology patterns showed higher proportion of NS1 antigen & antibody positive cases in adults and males compared to children & females respectively (Tables 2, 3, 4).

Table 2 Serology pattern in dengue.
Serology Pattern Number Percentage (%)
NS1 antigen3829
NS1 IgM1411
NS1 IgG1814
NS1 IgM, IgG118
IgM, IgG1511

Table 3 Age and gender distribution of serology pattern.
Serology pattern Adults Pediatric
Males Females Males Females
NumberPercentNumberPercent NumberPercent Number Percent
NS1 antigen161213106532
NS1 IgM65321143
NS1 IgG54542165
NS1 IgM, IgG65212111
IgM, IgG755432--
Total 51 38 21 22 

Table 4 Age & gender distribution of serology pattern in relation to population.
Serology pattern Adult males Adult females Pediatric males Pediatric females
Number Percent Number Percent Number Percent Number percent
NS1 antigen16/513113/3834 06/21 29 03/22 14
NS1 with antibody17/513310/3826 05/21 24 11/22 50
Antibody18/513515/3839 10/21 48 08/22 36

(2) Hematology parameters. (1) Haematocrit: A total of 72 cases with a rise in haematocrit over reference range for age & sex15was noted in our study (Table 5). (2) Total leucocyte count: Our study showed normal counts in 73/132 cases(55%), leucopenia in 47/132 cases (36%) and leucocytosis in 12/132 cases (9%). Leucopenia is a prominent feature in dengue (Table 6 & 7). (3) Differential count: Differential count was changed in 96 of 132 cases and was normal in 36 cases (27%), 88 cases of 132 showed lymphocytosis(67%) & 8 cases (6%) showed neutrophilia. Lymphocytosis is the predominant feature begins early in disease & is established late in the disease (Table 8). (4) Platelet count (thrombocytopenia): Thrombocytopenia was categorised on the basis of platelet count as; Mild with counts < 1.5 lakhs/cumm, with 29/132 (22%); Moderate with counts < 0.75 lakhs/cumm, with 28/132 (21%) and; Severe with counts < 0.5 lakhs/cumm with 75/132 (57%). Platelet count < 1.0 lakhs/cumm is one of the defining criteria for dengue haemorrhagic fever: we had 128 cases of 132 with counts < 1.0 lakhs/cumm (Table 9).

Table 5 Serology pattern in case with haematocrit rise.
Serology pattern Number positive Percentage NS1 & antibody association
NS1 antigen202866%
NS1 with antibody2738
Antibody only253472%
Total 72100

Table 6 Normal and increase total counts in association with serology.
Serology pattern Normal total count Increased total count
Number Percent Number Percent
NS1 antigen1622 - -
NS1 with antibody2230217
Antibody only35481083

Table 7 Serology patterns in decreased total counts (leucopenia).
Serology pattern Number Percent NS1 Ab association
NS1 antigen224787%
Ns1 with antibody1940
Antibody only61313%

Table 8 Serology patterns in association with differential count.
Serology patterns Neutrophilia Lymphocytosis* Association with antibody
Number Percent Number Percent
NS1 antigen2252630 
NS1 with antibody225273070%
Antibody only4503540
TOTAL 810088100 
*lymphocytosis- age adjusted values were used


Our study analysing age was in accordance with other studies with most cases in younger age with a slight male predominance perhaps due to occupation & recreational activities in men[11,16].

The serology pattern showed NS1 predominance followed by IgG. Except for IgM & IgG, all patterns showed concordance with others[17] whereas NS1, NS1 IgM patterns were similar to few studies[1,9].

We had a lower proportion of NS1 positive pattern with a higher proportion of antibody only pattern in children as against adults. In support of this, we observed that few studies had noted a higher risk of severe disease in children than adults[18]. There was no significant difference between the genders.

The immune response model in dengue indicates that NS1 antigen is the earliest marker detected in blood in dengue, between 1-9 days after fever. It is a marker of early diagnosis (acute phase) of disease. IgM antibody is detected from 5th day onwards till 2nd-3rd month, it indicates active/recent infection. IgG antibody from 7th day onwards, decreasing after 3rd month[1,7,18].

Hematocrit rises due to hemoconcentration attributed to plasma leakage as a result of increased capillary permeability occurring in the critical period. It aids in prognostication and management in dengue[19,20]. Analysis of our study showed that of 72 cases with a rise in haematocrit, there was a higher proportion in NS1 with antibody (38%) as against the lower proportion (28%) in NS1 antigen only pattern.

IgM is the earliest antibody to be detected from 5th day onwards. The results of our study suggests that the haematocrit rise is established only as a later event in dengue as few studies claimed[21,22] and is preceded by drop in blood counts[22]. We could not get data from similar studies to compare our results.

Total leucocyte count - Leucopenia is a major finding in dengue & caused by bone marrow suppression by virus[4,16]. Leucopenia aids in diagnosis, differentiation & prognostication of dengue[23,24,25]. In our study, we had 47/132 (36%) of leucopenia cases, 47% of these observed in NS1 antigen pattern whereas 13% were noted in antibody only pattern. There was a strong association with NS1 positivity (NS1 antigen & NS1 antibody) which was in concordance with other studies[26,27].

In contrast, normal counts were noted more (48%) in the antibody pattern rather than NS1 antigen pattern (22%). Our study indicated that leucocytosis was a later event mostly associated with antibody & none with NS1 antigen, in contrast to few studies which claimed it was an early event[13].

The results of our study suggests that leucopenia is an early marker of dengue infection as claimed by few studies[22,26] in view of NS1 antigen association.

Differential count - Bone marrow suppression causes a decrease in polymorphs with increase in lymphocytes especially atypical lymphocytes due to stimulation by nonspecific or specific viral antigens[24,27]. Lymphocytosis is a major finding in dengue especially atypical plasmacytoid lymphocytes[4,11]. The differential count (especially lymphocytosis) helps in differential diagnosis & prognostication in dengue[4,13,16].

We observed lymphocytosis in 67% of cases. A significant number of these (40%) were associated with antibody only pattern as against a lower proportion (30%) with NS1 antigen pattern. Neutrophilia was noted in 6% of cases & half the cases were associated with antibody only pattern.

Our study supports the observation of few studies that early in illness there is decrease in neutrophils with lymphocytosis[27]. Lymphocytosis is a later event predominantly and is established as disease progresses[13].

We could not get data from similar studies to confirm our findings.

Thrombocytopenia in dengue is caused by bone marrow suppression & immune mediated clearance of platelets[28]. Thrombocytopenia aids in diagnosis of dengue & helps in its differential diagnosis[4]. It is useful as a diagnostic, predictive & recovery parameters of DHF[10].

We had a total of 132 cases of thrombocytopenia. The results in severe thrombocytopenia category showed higher proportion of cases with the antibody only pattern (43%) as against the lower proportion in NS1 antigen pattern (21%). This was in concordance with few studies which claimed increased association of thrombocytopenia with antibody patterns[8,29]. A few studies noted increased association with NS1 antigen[1,9]. Others claimed more association of NS1 with antibody[11]. A few studies have found no correlation between the two[2]. However, on comparison between studies, it was found inaccurate due to varying thresholds of platelet count, varying methods of correlation, inclusion of normal & high platelet counts in the studies & number of cases included in the study.

The results in our study was in agreement with the observation made in few studies that platelet counts start decreasing by 3rd/4th day to 7th day10,30 in view of stronger association with antibody pattern.

Limitations of the study

Our study was limited by: (1) relatively smaller study size; (2) very few similar studies to compare our data & derive conclusions; (3) blood tests were done on random samples & this aspect suffered from lack of standardisation.


In India, frequent dengue epidemics strain the limited resources of the public health system. This study explores the utility of simple, easy, rapid & cost effective tests like serology & hematology, also as a supplement & substitute to one other in diagnosis & prognosis of the dengue spectrum especially in rural & peripheral areas.


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Peer reviewer: Raul Morales-Borges


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