• Users Online: 285
  • Print this page
  • Email this page

 
Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 11  |  Issue : 4  |  Page : 150-155

Hematological indices as predictors of mortality in dengue shock syndrome: A retrospective study


1 S.P. Medical College, Bikaner, Rajasthan, India
2 AIIMS Jodhpur, Rajasthan, India

Date of Submission20-Jun-2022
Date of Decision24-Jul-2022
Date of Acceptance17-Aug-2022
Date of Web Publication06-Sep-2022

Correspondence Address:
Ketan Bhatnagar
S.P. Medical College, Bikaner, Rajasthan, India
India
Login to access the Email id

Source of Support: This study received no extramural funding, Conflict of Interest: None


DOI: 10.4103/2221-6189.355312

Rights and Permissions
  Abstract 

Objective: To explore predictive hematological parameters on admission which are associated with mortality in NS1 positive dengue shock syndrome patients.
Methods: Demographic characteristics, hematological parameters, and the outcome of NS1 positive dengue shock syndrome patients without any comorbidity and coexisting infections were collected from the Intensive Care Unit and the results were compared between the survivor and non-survivor groups.
Results: The mean age was (30.77±11.48) years and 56 (56.6%) patients were males. Out of the total 99 patients, 72 (72.27%) patients were successfully discharged and 27 (27.27%) patients eventually succumbed to death. The most common hematological finding was thrombocytopenia (95.95%), followed by anemia (52.52%) and decreased mean platelet volume (37.37%). After controlling other variables, logistic regression analysis showed that absolute neutrophil count and mean platelet volume were associated with mortality.
Conclusions: Total leucocyte count, absolute neutrophil count, and total platelet count are significantly higher, and mean platelet volume is significantly lower in the non-survivor group as compared to the survivor group. Absolute neutrophil count and mean platelet volume are predictors associated with mortality.

Keywords: Dengue shock syndrome; NS1; Complete blood count; Thrombocytopenia; Leucocytosis; White blood cell; Absolute neutrophil count; Mean platelet volume


How to cite this article:
Gauri L A, Bhatnagar K, Sameja P, Nehara HR, Saini K, Dutt R, Bhatnagar B, Khokhar MS, Kumar V, Garg A. Hematological indices as predictors of mortality in dengue shock syndrome: A retrospective study. J Acute Dis 2022;11:150-5

How to cite this URL:
Gauri L A, Bhatnagar K, Sameja P, Nehara HR, Saini K, Dutt R, Bhatnagar B, Khokhar MS, Kumar V, Garg A. Hematological indices as predictors of mortality in dengue shock syndrome: A retrospective study. J Acute Dis [serial online] 2022 [cited 2022 Oct 3];11:150-5. Available from: https://www.jadweb.org/text.asp?2022/11/4/150/355312




  1. Introduction Top


Dengue is an acute febrile illness caused by dengue RNA virus which belongs to the Flaviviridae family[1]. Dengue was first described by Benjamin Rush in the eighteenth century and the word “dengue” was taken from the Swahili word “Ka-dinga pepo” which means a seizure induced by an evil spirit[2]. It occurs due to bite of Aedes mosquito and is found in tropical and subtropical regions. According to World Health Organization, the incidence of dengue infection has risen tremendously with around half of the world population at risk and an estimated incidence of 390 million cases per year, and cases in Asian countries account for 70% of the burden in the world[3]. As per data provided by the Director General of Health Services, in the year 2021, India recorded about 193 245 cases with around 20 749 cases from Rajasthan accounting for 10.7% of the national burden. The rising trend of dengue in the past few years has become a global challenge and is primarily credited to population migration from rural to urban areas with sub-standard living patterns causing a higher density and providing breeding places for mosquitoes. The majority of the infected people are asymptomatic or have only mild symptoms such as fever, some may develop severe illness and in a few of them, it can become life-threatening[4]. The clinical course of the disease is divided into 3 phases viz. febrile, critical, and recovery phases. The incubation period is mostly about 4 to 7 days. It is also called “break-bone fever” because of the joint and muscle pain associated with this infection. The commonly observed hematologic changes in dengue fever include thrombocytopenia, leucopenia, and hemoconcentration[5].

Approximately 2%-5% of patients who had dengue infection develop severe complications, so it is very essential to stratify these patients and effectively look for those who require urgent intervention. This is important in resource-limited countries to reduce an overburden on the health care system[6]. Our study aims to describe the potential predictive hematological parameters which are associated with mortality in NS1 positive dengue shock syndrome (DSS) patients.


  2. Patients and methods Top


2.1. Study setting and population

This was a retrospective study and included adult patients (≥18 yrs) with NS1 positive DSS without any comorbidity and coexisting infection who were admitted to the Intensive Care Unit at S.P. Medical College and P.B.M. Hospital, a tertiary care center in North Western Rajasthan during dengue outbreak between September 2021 to November 2021.

2.2. Ethical statement

The study is approved by the Institutional Ethics and Research Board of S.P. Medical College, Bikaner (Rajasthan) vide approval number F 29 (Acad) SPMC/2022/2200, dated 30/04/2022.

2.3. Definitions

As per WHO classification, dengue hemorrhagic fever was labelled based on the presence of hemorrhage, fever, thrombocytopenia, and plasma leak suggesting increased vascular permeability like hemoconcentration, pleural effusion, ascites, and hypoalbuminemia[7]. DSS denotes dengue hemorrhagic fever with marked plasma leakage showing narrow pulse pressure or hypotension. Increased hematocrit (Hct) was considered as a value >45% while thrombocytopenia was defined as a total platelet count of <1.5 lac/mm3. Anemia was defined as hemoglobin less than 13 g/dL for males and less than 12 g/dL for females. Leucocytosis was considered with white blood cell count (WBC) count >11 000/mm3, neutrophilia was considered with absolute neutrophil count (ANC)>7700/mm3, and decreased mean platelet volume (MPV) was labeled with a value <9.4 fl[8],[9].

2.4. Data collection

Parameters like demographic, clinical, hematological, and the outcome of NS1 positive DSS patients were collected from the Intensive Care Unit. A total of 99 DSS patients were divided into two groups: one included the patients who survived (survivor; n=72) and the other included the patients who died (non-survivor; n=27) during treatment. Hematological parameters on admission were compared between the two groups and analyzed.

2.5. Primary outcome

The primary outcome was in-hospital death.

2.6. Laboratory investigations

Complete blood count of the NS1 positive DSS patients was studied for individual hematological indices like hemoglobin (Hb), mean corpuscular volume (MCV), Hct, WBC, ANC, absolute lymphocyte count (ALC), absolute monocyte count (AMC), platelet count, and MPV.

2.7. Statistical analysis

The statistical analysis was done using SPSS software version 16.0. The continuous variables were represented as median (Q1, Q3) or mean±SD while percentage and frequency were used to represent categorical variables. The Mann-Whitney test and Chi-square test were used to compare the two groups. The significance level of our study was α=0.05.


  3. Results Top


3.1. Demographic characteristics

The demographic characteristics of the patients are shown in [Table 1]. The mean age was (30.77±11.48) years and 56 (56.6%) patients were male. Fifty-four (54.5%) patients belonged to the urban area and 45 (45.5%) belonged to the rural area. Out of the total 99 patients, 72 (72.27%) patients were successfully discharged and 27 (27.27%) patients eventually succumbed to death [Figure 1].
Table 1: Demographic characteristics.

Click here to view
Figure 1: The study flowchart.

Click here to view


Among survivors, the mean age was (31.25±11.17) years, 41 (56.9%) patients were male and 40 (55.6%) patients lived in urban areas while in non-survivor group, the mean age was (29.52±12.41) years, 15 (55.6%) patients were male and 14 (51.9%) lived in urban areas.

3.2. Hematological parameters

The hematological parameters of the patients are shown in [Table 2] and [Table 3]. Thrombocytopenia was present in 95 (95.95%) patients and was the most common hematological finding, followed by anemia in 52 (52.52%) patients, decreased MPV in 37 (37.37%) patients, neutrophilia in 8 (8.08%) patients, and leucocytosis in 7 (7.07%) patients. Numbers of patients with leucocytosis (P=0.001) and neutrophilia (P<0.001) were significantly different between the two groups.
Table 2: Comparison of laboratory parameters in the survivor and non-survivor group.

Click here to view
Table 3: Laboratory findings in the survivor and non-survivor group (n, %).

Click here to view


In this study, the median WBC count was significantly higher in non-survivors as compared to survivors [6.8 (3.7, 10.1) cells×103/μL vs. 4.2 (3.2, 5.8) cells×103μL, P=0.001]. The median ANC was also significantly higher in the non-survivors group [4.3 (2.8, 8.4) cells×103/L vs. 2.2 (1.5, 3.0) cells×103/L, P<0.001]. The median platelet count was significantly higher in the non-survivors group [44.0 (3.02, 79.0) cells×103/μL vs. 31.5 (21.5, 50.0) cells×10>L; P=0.006]. The median MPV was significantly lower in non-survivors [8.4 (7.4, 10.1) vs. 9.3 (8.6, 10.4); P=0.02]. After controlling other variables, logistic regression analysis showed that the predictors associated with mortality were ANC and MPV [Table 4].
Table 4: Binary logistic regression analysis of variables associated with mortality.

Click here to view



  4. Discussion Top


The complete blood count analysis is an effective and noncumbersome way to predicate the outcome of dengue patients. In this study, the in-hospital deaths were significantly associated with higher WBC count, higher ANC, higher platelet count, and lower MPV value. Patients with leucocytosis and neutrophilia were significantly higher in the non-survivors group. The mortality in the study group was 27.27%. Logistic regression analysis after controlling other variables showed that the predictors associated with mortality were ANC and MPV.

In this study, the mean age of the study group was (30.77±11.48) years, 56 (56.6%) patients were male and 54 (54.5%) patients lived in urban areas, which is similar to other studies done in the Indian subcontinent[10],[11],[12]. Jain et al[10] reported a mean age of (30.9±13.9) years with males as the majority. Baitha et al[11] also has similar conclusion. The higher male and urban predominance may be due to more outdoor exposure of males and the higher population density in urban areas with a substandard living pattern.

The median WBC count of this study was significantly higher in the non-survivors group. Among the non-survivors, 20 deaths were attributable directly to dengue, 3 deaths were due to ventilator- associated pneumonia, 3 deaths were due to gastrointestinal bleeding with septic shock and 1 died due to intracranial hemorrhage. Leucopenia is a well-known manifestation in the case of dengue infection and this study demonstrated higher WBC in the nonsurvivors group. The results were in line with other studies[11],[13],[14],[15]. Singhal et al[13] reported a high WBC count in all fatalities and it has been reported earlier also as a poor prognostic marker. Another study by Amâncio et al reported that the factors correlated with mortality were subsequent comorbidities, difficulty of breathing, lassitude, higher WBC, elevated serum creatinine, and decreased serum albumin levels[14]. Baitha et al[11] concluded that a higher leucocyte count, acute kidney injury, and tachypnea at time of admission were significantly associated with higher in-hospital mortality. Another study conducted by Eu-Ahsunthornwattana et al[15] reflected the absence of leucopenia as a marker of severe dengue infection. The associated leucocytosis might be due to gastrointestinal bleed with simultaneous bacteremia, meningitis, or ventilator-associated pneumonia. Therefore, empirical antibiotics should be administered to dengue patients with leucocytosis, altered sensorium, and gastrointestinal bleed[16],[17].

ANC was statistically higher in the non-survivor group as compared to the survivor group suggesting bacterial infection. Ralapanawa et al[18] also showed higher leucocyte and neutrophil values in patients with dengue hemorrhagic fever.

Thrombocytopenia was the most common hematological finding in this study but no association was found with the primary outcome. Possible mechanisms of thrombocytopenia include (I) inhibition of bone marrow progenitor cells due to dengue virus, (II) increased apoptosis leading to platelet destruction, (III) complement-mediated lysis, (IV) production of anti-platelet antibodies, (V) disseminated intravascular coagulation leading to platelet consumption. The median total platelet count was significantly higher in the nonsurvivor group. This suggests that the platelet count could not predict mortality, which has also been mentioned in some studies[10],[11],[19]. A study done by Jain et al[10] concluded that platelet counts neither correlate with bleeding manifestations nor determine the disease outcome of dengue infection. Baitha et al[11] also showed that neither bleeding manifestation nor thrombocytopenia determined the mortality. In the study of Chaloemwong et al[19], prolonged duration of thrombocytopenia was seen more commonly in severe dengue patients and was considered to be a predictor of severity rather than total platelet count. The bleeding manifestation in case of dengue infection is more due to coinciding platelet dysfunction and therefore efforts should not be made to just increase the platelet count by transfusion and possessing the patients to undue risk of transfusion reaction. This result was not consistent with some other studies. A study by Pinto et al[20] from Brazil showed that age >55 years, hematuria, gastrointestinal bleeding, and low platelet count were associated with high mortality. Nandwani et al[21] in their study concluded that initial thrombocytopenia, initial leucocytosis, and low MPV are probable predictors of fatal outcomes in disease progression.

The median MPV value in our study was significantly lower in the non-survivor group as compared to the survivor (P=0.02). MPV is an indicator of bone marrow activity, a high MPV denotes increased megakaryocytic activity whereas a low MPV denotes bone marrow suppression and is associated with high chances of bleeding[22]. Studies have shown that dengue fever is associated with a lower value of MPV[21],[22],[23]. Nandwani et al[21] in their retrospective analysis observed that low MPV was associated with worse outcome in course of disease. Nehara et al[23] in their study regarding platelet indices in dengue patients showed that low MPV and low PCT (plateletcrit) has appreciable specificity and sensitivity for dengue fever and a low PCT and low platelet count can be used as a predictor of severity in dengue infection. A study by Khatri et al[24] among dengue patients found no significant abnormality regarding MPV, platelet distribution width or PCT compared to controls. Other studies have shown that MPV is not a considerable prognostic marker in dengue infection[22]. Since only a few studies explored the association between platelet indices and disease outcomes, further research is required to confirm the same.

In this study, the mortality rate was 27.27%. This could be due to more sick patients being admitted to the hospital as it is a tertiary care center and therefore represents the Berksonian bias. Case fatality in dengue has varied from 0.5%-5% but in cases of DSS it has ranged up to 44%[15].

This study had a few limitations. It was a single-center study with a small sample size which included only those patients who were admitted to the Intensive Care Unit. The results may differ depending on the geography of the areas, genetic makeup of the patients, and the prevalent serotype. The strength is that a complete blood count can easily be used to stratify the severity of dengue easily and cost- effectively in developing countries where well-equipped health infrastructure is lacking.

In conclusion, total leucocyte count, ANC, and total platelet count are significantly higher, and MPV was significantly lower in the nonsurvivor group as compared to the survivor group. After controlling other variables, predictors associated with mortality are ANC and MPV. Hematological indices are objective measures as compared to the subjective findings like generalized weakness, pain abdomen, and headache and therefore are more important in determining the severity and predicting the outcome.

Conflict of interest statement

The authors report no conflict of interest.

Funding

This study received no extramural funding.

Authors’ contributions

L.A.G., H.R.N., and K.B. contributed to the project design, data interpretation, drafting, and revising; P.S., K.S., and R.D. contributed to statistical analysis, data interpretation, and submission; B.B., M.S.K, V.K., and A.G. contributed to collection of data, statistical analysis, and data interpretation. All authors contributed equally to the manuscript.



 
  References Top

1.
Gubler DJ. The global emergence/resurgence of arboviral diseases as public health problems. Arch Med Res 2002; 33(4): 330-342.  Back to cited text no. 1
    
2.
The Fielding H. Garrison Lecture: “Break-Bone” fever in Philadelphia, 1780: Reflections on the history of disease. Bull Hist Med 2016; 90(2): 193-221.  Back to cited text no. 2
    
3.
WHO. Dengue and severe dengue. [Online]. Available from: http://www.who.int/news-room/fact-sheets/detail/dengue-and-severe-dengue [Accessed on 2022 Jan 20].  Back to cited text no. 3
    
4.
Whitehorn J, Farrar, J. Dengue. Brit Med Bull 2010; 95(1): 161-173,  Back to cited text no. 4
    
5.
Ali N, Usman M, Syed N, Khurshid M. Haemorrhagic manifestations and utility of haematological parameters in dengue fever: A tertiary care centre experience at Karachi. Scand J Infect Dis 2007; 39(11-12): 1025-1028.  Back to cited text no. 5
    
6.
Jaenisch T, Tam DTH, Kieu NTT, Van Ngoc T, Nam NT, Van Kinh N, et al. Clinical evaluation of dengue and identification of risk factors for severe disease: Protocol for a multicentre study in 8 countries. BMC Infect Dis 2016; 16: 120.  Back to cited text no. 6
    
7.
World Health Organization. Dengue hemorrhagic fever: diagnosis, treatment, prevention and control. Geneva: WHO; 1997.  Back to cited text no. 7
    
8.
Tahir N, Zahra F. Neutrophilia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2022.  Back to cited text no. 8
    
9.
CBC (Complete Blood Count). [Online]. Available from: http://www.healthcare.uiowa.edu/path_handbook/rhandbook/test299.html [Accessed on 2022 Apr 14].  Back to cited text no. 9
    
10.
Jain S, Mittal A, Sharma SK, Upadhyay AD, Pandey RM, Sinha S, et al. Predictors of dengue-related mortality and disease severity in a tertiary care center in North India. Open Forum Infect Dis 2017; 4(2): ofx056.  Back to cited text no. 10
    
11.
Baitha U, Shankar SH, Kodan P, Singla P, Ahuja J, Agarwal S, et al. Leucocytosis and early organ involvement as risk factors of mortality in adults with dengue fever. Drug Discov Ther 2020; 14(6): 313-318.  Back to cited text no. 11
    
12.
Rabbani MU, Aslam M, Zaheer MS, Ashraf MU. Clinical and laboratory profile of dengue fever in a North Indian Tertiary Hospital. J Assoc Physicians India 2018; 66(4): 37-39.  Back to cited text no. 12
    
13.
Singhal T, Kothari V. Clinical and laboratory profile of fatal dengue cases at a tertiary care private hospital in Mumbai, India. Am J Trop Med Hyg 2020; 103(3): 1223-1227.  Back to cited text no. 13
    
14.
Amâncio FF, Heringer TP, de Oliveira C da CHB, Fassy LB, de Carvalho FB, Oliveira DP, et al. Clinical profiles and factors associated with death in adults with dengue admitted to intensive care units, Minas Gerais, Brazil. PLoS One 2015; 10(6): e0129046.  Back to cited text no. 14
    
15.
Eu-Ahsunthornwattana N, Eu-ahsunthornwattana J, Thisyakorn U. Peripheral blood count for dengue severity prediction: A prospective study in thai children. Pediatrics 2008; 121(Supplement 2): S127-S128.  Back to cited text no. 15
    
16.
Lee IK, Liu JW, Yang KD. Fatal dengue hemorrhagic fever in adults: Emphasizing the evolutionary pre-fatal clinical and laboratory manifestations. PLoS Negl Trop Dis 2012; 6(2): e1532.  Back to cited text no. 16
    
17.
Thein TL, Ng EL, Yeang MS, Leo YS, Lye DC. Risk factors for concurrent bacteremia in adult patients with dengue. J Microbiol Immunol Infect 2017; 50(3): 314-320.  Back to cited text no. 17
    
18.
Ralapanawa U, Alawattegama ATM, Gunrathne M, Tennakoon S, Kularatne SAM, Jayalath T. BMC Res Notes 2018; 11(1): 400.  Back to cited text no. 18
    
19.
Chaloemwong J, Tantiworawit A, Rattanathammethee T, Hantrakool S, Chai-Adisaksopha C, Rattarittamrong E, et al. Useful clinical features and hematological parameters for the diagnosis of dengue infection in patients with acute febrile illness: a retrospective study. BMC Hematol 2018; 18: 20.  Back to cited text no. 19
    
20.
Pinto RC, de Castro DB, de Albuquerque BC, Sampaio V de S, dos Passos RA, da Costa CF, et al. Mortality predictors in patients with severe dengue in the State of Amazonas, Brazil. PLoS One 2016; 11(8): e0161884.  Back to cited text no. 20
    
21.
Nandwani S, Bhakhri BK, Singh N, Rai R, Singh DK. Early hematological parameters as predictors for outcomes in children with dengue in northern India: A retrospective analysis. Rev Soc Bras Med Trop 2021;54: e05192020.  Back to cited text no. 21
    
22.
Wiwanitkit V. Mean platelet volume in the patients with dengue hemorrhagic fever. Platelets 2004; 15(3): 185.  Back to cited text no. 22
    
23.
Nehara HR, Meena SL, Parmar S, Gupta BK. Evaluation of platelet indices in patients with dengue infections. Int J Sci Res 2016; 5(7): 78-81.  Back to cited text no. 23
    
24.
Khatri S, Sabeena S, Arunkumar G, Mathew M. Utility of platelet parameters in serologically proven dengue cases with thrombocytopenia. Ind J Hematol Blood Transfus 2018; 34(4): 703-706.  Back to cited text no. 24
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  2. Patients and ...
  In this article
Abstract
1. Introduction
3. Results
4. Discussion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed350    
    Printed4    
    Emailed0    
    PDF Downloaded36    
    Comments [Add]    

Recommend this journal