Published in IJCP June 2020
Research article
Correlation of Hematological Parameters with Right-sided Pleural Effusion in Pediatric Dengue Cases: A Cross-sectional Study
June 22, 2020 | Harish GV, Rajashekar Reddy Tupalli
     


Abstract

Background: Capillary leak in dengue presents as ascites, pleural effusion and pericardial effusion. Among the cases of dengue admitted to our hospital in past 2 years, we have observed that right side pleural effusion was more common than left side or bilateral effusion. Objectives: 1) To study about hematological parameters and radiological findings in cases of dengue in pediatric age group. 2) To correlate hematological parameters with radiological findings of right-sided pleural effusion. Study design: Cross-sectional study. Participants: This study was conducted at our tertiary care teaching hospital Prathima Institute of Medical Sciences (PIMS), Karimnagar in Telangana. A total of 138 cases were included in the study and their hematological parameters were correlated with the radiological findings of pleural effusion. Investigations: Investigations included complete hemogram on the day of admission, on the day of diagnosis of pleural effusion and at discharge. Radiological investigations included chest X-ray, ultrasonogram of abdomen and chest. Results: Out of 138 cases, 71 (51%) had pleural effusion, of which, 46 cases (64.78%) had bilateral effusions with right side more often affected than left. Twenty-one (29.57%) cases had only right-sided pleural effusion. The mean platelet count and hematocrit were 67,640/µL and 31.8%, respectively on the day of pleural effusion. Conclusion: In cases of dengue with thrombocytopenia Grade 4 (20,000-50,000/µL), pleural effusion is more common on the right side detected by radiological investigation on Day 4 of illness.

Keywords: Dengue, radiological findings, right side pleural effusion, thrombocytopenia

Dengue fever is a tropical viral disease caused by the dengue virus transmitted by Aedes aegypti mosquito. Dengue virus is an arbovirus with single-stranded RNA belonging to genus Flavivirus; it has four serotypes - DENV-1, 2, 3 and 4. A fifth serotype, DENV-5, has been reported in Malaysia but the exact characterization of the virus has not been done.1

In 2017, a total of 1,88,401 cases were reported in India and Telangana recorded 5,369 cases during that period.2 First infection with dengue virus leads to dengue fever and second infection with different serotype leads to dengue with warning signs and severe dengue due to increased capillary permeability, causing fluid losses in third spaces, intravascular fluid depletion and shock. The immune complex of antibody and virus affects the macrophages leading to antibody-dependent enhancement and release of cytokines, cascading capillary leak.3 Research seems to point towards disturbance in the endothelial glycocalyx layer in dengue leading to capillary leaks and bleeding manifestations.4 Pleural effusion usually develops during the critical phase on Day 4-6 of illness.5 Radiological investigations like chest X-ray, ultrasonogram (USG) and computed tomography (CT) scan have been used in diagnosing pleural effusion.6-8

The current study was conducted at tertiary care teaching hospital, Prathima Institute of Medical Sciences, Karimnagar in Telangana, as we have observed in past 2 years that the incidence of right side pleural effusion was more common than left side or bilateral effusion, and hence we have correlated hematological parameters with the radiological finding of right-sided pleural effusion.

Methods

This was a cross-sectional study conducted during the period July 2018 to November 2018, in children admitted in pediatric ward and ICU at our hospital diagnosed as dengue. All children had complete hemogram and dengue serology done at admission. Cases having capillary leak with third space losses, respiratory distress and clinically diagnosed cases of pleural effusion were subjected to chest X-ray and/or USG. In these cases, complete hemogram was repeated on the day of radiological diagnosis of pleural effusion.

Children with existing congenital cardiac disorders, underlying pulmonary diseases and renal disorders were excluded from the study. A total of 138 cases were included in the study. All the data was entered into Microsoft Excel Sheet and it was analyzed using Statistical Package for Social Sciences (SPSS), Version 21.

Results

Of the 138 cases in the study, 76 (55.07%) were male and 62 (44.92%) were female. Twenty (14.49%) cases were aged less than 1 year, 27 (19.5%) cases were between 1 year and 5 years, 49 (35.50%) cases were between 6 and 10 years, 33 (23.91%) cases were between 11 and 15 years and 9 (6.52%) cases were between 15 and 18 years (Fig. 1).

Figure 1. Age and sex distribution of cases in the study.

Thirty-one (22.4%) cases were diagnosed as probable dengue, 88 (63.7%) cases were diagnosed as dengue with warning signs and 19 (13.7%) cases were severe dengue.

A total of 71 (51%) cases developed pleural effusion. Of these, 46 (64.78%) cases had bilateral pleural effusion with right side more often affected than left (including both USG and chest X-ray), 21 (29.57%) cases had only right side pleural effusion (USG and chest X-ray), 3 (4.2%) cases had pleural effusion on left side (USG and chest X-ray) and 1 (1.4%) case had bilateral equal pleural effusion (Fig. 2).

Figure 2. Case distribution according to site of pleural effusion.

The mean day at which pleural effusion developed was 4th day of illness.

The mean platelet count on the day of admission was 76,460/µL. The mean platelet count on the day of radiological diagnosis of pleural effusion was 67,640/µL. The mean platelet count at discharge was 1,24.360/µL (Table 1).

Table 1. Mean Platelet and Hematocrit of All Cases

Day

Admission

Day of pleural effusion

Discharge

Mean platelet (x103/μL)

76.46

67.64

124.36

Mean hematocrit (%)

32.41

31.8

30.68

The mean hematocrit at admission was 32.41%. The mean hematocrit on the day of pleural effusion was 31.8%. The mean hematocrit at discharge was 30.68% (Table 1).

The mean platelet count and hematocrit in bilateral pleural effusion cases were 85,000/µL and 24.90%, respectively (Table 2).

The mean platelet count and hematocrit in cases with bilateral pleural effusion with right > left side were 51,670/µL and 31.51%, respectively (Table 2).

Table 2. Mean Platelet and Hematocrit for the Pleural Effusion Cases

Pleural effusion site

Mean platelet (x103/μL)

Mean hematocrit (%)

Bilateral

85

24.90

Bilateral R > L

51.67

31.51

Right side

62.8

34.03

Left side

62.33

28.50

No effusion

80.08

31.55

The mean platelet count and hematocrit in right side pleural effusion cases were 62,800/µL and 34.03%, respectively (Table 2).

The mean platelet and hematocrit in cases with left side pleural effusion were 62,330/µL and 28.50%, respectively (Table 2).

Among 138 cases, 119 (86.2%) cases were NS1 positive, of which 62 (52.1%) cases had pleural effusion, with 43 cases having bilateral pleural effusion with right > left side, 17 cases had right side pleural effusion and only 2 cases had effusion on left side. 

In our study, we graded thrombocytopenia on the day of detection of pleural effusion into 5 grades - Grade 1 included cases with platelet count >1.5 lakh/µL, Grade 2 included cases with platelet count between 1 lakh and 1.5 lakh/µL, Grade 3 with platelet count between 50,000 and 1 lakh/µL, Grade 4 with platelet count 20,000-50,000/µL and Grade 5 with platelet count <20,000/µL.

Among these, pleural effusions were more common with platelet counts between 20,000-50,000/µL, i.e., in Grade 4 with 33 (46.47%) cases, followed by Grade 3 with 25 cases (35.2%), Grade 2 and Grade 5 included 5 (7%) cases and Grade 1 had 3 (4.2%) cases among cases with pleural effusion (Table 3).

Table 3. Pleural Effusion Site vs. Thrombocytopenia Grading

Pleural effusion (total)

Bilateral

Bilateral R > L

Right

Left

Platelet >1.5 lakh/μL (3)

0

2

1

0

Platelet 1-1.5 lakh/μL (5)

0

3

1

1

Platelet 50 k-1 lakh/μL (25)

1

14

10

0

Platelet 20 k-50 k/μL (33)

0

23

8

2

Platelet <20 k/μL (5)

0

4

1

0

Total

1

46

21

3

Right-sided pleural effusion had higher incidence in Grade 4 thrombocytopenia, i.e., with platelet count between 20,000 and 50,000/µL, followed by in Grade 3, i.e., 50,000-1 lakh/µL.

Discussion

Dengue is an arboviral disease caused by dengue virus categorized under Flavivirus, and includes five serotypes. Although the serotypes are antigenically similar, they are different enough to elicit cross protection only for few months after infection with any one of them. Infection confers lifelong immunity for that serotype. The vector for virus is female Aedes aegypti mosquito, which becomes infective after an extrinsic incubation period between 5 and 33 days at 25°C, and between 2 and 15 days at 30°C. Dengue begins abruptly after an intrinsic incubation period of 3-10 days.9 The host immune response plays an important role in the pathogenesis of dengue fever. Many pathogenic mechanisms have been proposed, like immune complex-mediated mechanism; T-cell–mediated antibodies cross-reacting with vascular endothelium, enhancing antibodies, complement and its products, cytokines and chemokines. The most accepted theory stays the virus strains enhancing the antibodies and memory T-cells in secondary infection causing release of cytokines which act on the vascular endothelium, platelets and various other organs causing vasculopathy, coagulopathy and shock.3

The course of illness in dengue is in three phases - the febrile phase, the critical phase and the recovery (convalescent) phase. The cases are defined and classified into three groups based on the severity of the clinical manifestations as probable dengue, dengue with warning signs and severe dengue.10 In our study of 138 cases, 22.4% were cases of probable dengue, 63.7% were dengue with warning signs and 13.7% were severe dengue. In a similar study conducted by Kabilan et al,11 in a tertiary care hospital in South India, among 143 cases, 65% had dengue fever, 11.2% had dengue hemorrhagic fever and 23.8% had dengue shock syndrome. In our study which extended over a period of 5 months, there were 138 cases with 20 (14.4%) cases being infants, 27 (19.5%) cases aged 1-5 years and 82 (59.4%) cases aged 6-15 years. This is comparable with the study by Kabilan et al,11 which extended over 3 months and had total of 143 cases, 29 (20%) being infants, 41 (28.7%) being between 1 year and 5 years and 51% being 6-15 years. In both the studies, the incidence of dengue was more in the age group 6-15 years.

Capillary leakage occurs usually between 3rd and 7th day of illness and patients present with hemoconcentration, pleural effusion and ascites during which the patient may be afebrile. The anti-NS1 antibodies act as autoantibodies that cross-react with the endothelium and the platelets, which triggers the intracellular signaling causing changes in capillary permeability, disturbing the integrity of the glycocalyx layer of endothelial cells. In our study, 64.78% cases had bilateral pleural effusion with right side more than left, 29.57% had isolated right side pleural effusion, while only 4.2% cases had isolated left side pleural effusion. Previously, many studies had mentioned pleural effusion as one of the manifestations of dengue. In a study conducted by Venkata Sai et al,7 right side pleural effusion had more incidence (71.87%) than left side pleural effusion (21.87%) and the effusion was detected between 5th and 7th day, while the mean day of detection of pleural effusion in our study was 4th day. Similarly, in a study conducted by Santhosh et al,12 bilateral (26%) and right side (22.9%) pleural effusion had higher incidence when compared to the left side effusion (1 patient).

In a study conducted by Shabbir et al,13 left side pleural effusion was more common with left side effusion noted in 50% cases, right side effusion in 40% cases and bilateral in 10% cases.

Thrombocytopenia occurs due to the destruction of platelets by the autoantibodies, disseminated intravascular coagulation (DIC), bone marrow suppression during early phase of disease and peripheral sequestration of platelets. In our study, we have correlated thrombocytopenia with pleural effusion, and we have observed that the mean platelet count in cases of bilateral pleural effusion right > left side was less when compared to other sites of pleural effusion. In the study conducted by Santhosh et al,12 pleural effusion was correlated with platelet count, and they found that effusion was more common with platelet count <40,000/µL. In our study, 46.47% of the cases with pleural effusion had platelet count between 20,000 and 50,000/µL, i.e., Grade 4 thrombocytopenia.

Conclusion

In cases of dengue with thrombocytopenia Grade 4 (20,000-50,000/µL), pleural effusion is more common on the right side detected by radiological investigation on Day 4 of illness.

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