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Effect of vitamin E on thrombocytopenia in dengue fever

ORIGINAL ARTICLE

Arvind Vaish, Sudhir Verma, Abhishek Agarwal1, Lokesh Gupta, Manish Gutch
Departments of Medicine, and 1Pulmonary Medicine, Chhatrapati ShahuJi Maharaj Medical University (Formerly King George’s Medical
University), Lucknow, Uttar Pradesh, India

ABSTRACT
Context: Dengue fever frequently causes thrombocytopenia for which there is no satisfactory treatment. Aim: To
evaluate the effect of vitamin E on thrombocytopenia in dengue fever. Settings and Design: A tertiary teaching
hospital during a recent outbreak of dengue fever in the area. Materials and Methods: Patients of dengue fever
(as per WHO criteria) with thrombocytopenia and platelet counts between 10 × 103/mm3 and 100 × 103 /mm3
seen during September 1, 2010 to November 30, 2010 were enrolled. After detailed history and clinical evaluation,
the patients were randomized to two groups - group I which received vitamin E 400 mg (Evion, Merck) once daily
along with standard treatment and group II which received standard treatment only. The platelet counts, bleeding
manifestations, requirement for platelet transfusion were serially monitored for up to 1 week in these cases.
Statistical Analysis Used: Percentage, mean, standard error of mean, Mann-Whitney U test, and Chi-square test.
Results: We enrolled 66 cases (group I - 33 and group II - 33). Mean platelet count at baseline in both the groups
was similar (group I - 28.39 ± 1.61 × 103/mm3 and group II - 27.64 ± 1.65 × 103/mm3) (P > 0.05). We observed that
the mean platelet count on day 4 in group I (vitamin E) was significantly higher (Mean - 122.19 ± 9.98 × 103/mm3;
CI 95% -102.63 × 103/mm3 - 141.76 × 103/mm3) than in group II (Mean - 92.57 ± 7.93 × 103/mm3; CI 95% - 77.03 ×
103/mm3 - 108.11 × 103/mm3) (P = 0.0436). Similar findings were also observed on day 7 in the two groups. Platelet
transfusion was required in less cases in group I [2 out of 33 (6.06%)] as compared to group II [5 out of 33 (15.15%)].
Conclusion: We conclude that vitamin E is beneficial in thrombocytopenia in dengue fever and results in faster
increase in the platelet counts.

Key words: Bleeding, dengue fever, thrombocytopenia, vitamin E

Introduction antioxidant and free-radical scavenging properties and


may therefore help in these cases.[5,6] Hence, in the
In recent years, dengue fever has become a worldwide present study, we have evaluated the effect of vitamin E
public health concern. In India, epidemics are becoming on thrombocytopenia in the cases of dengue fever.
more frequent and are exhausting the limited public
health resources. Untreated, mortality of dengue fever Materials and Methods
can be as high as 20%, whereas if recognized earlier and
managed properly mortality is less than 1%.[1] The major Study Design
threat of dengue fever is from thrombocytopenia and Prospective randomized open blinded evaluation
consequently from the bleeding manifestations. There (PROBE) design.
is as yet no satisfactory treatment for thrombocytopenia
in these cases.[2] The pathogenesis of thrombocytopenia Study Population
in dengue fever is not clear but increased oxidative Inclusion criteria: Patient of dengue fever (as per WHO
stress may have a role.[3,4] Vitamin E which has criteria[2]) with thrombocytopenia (platelet count
between 10 × 103/mm3 and 100 × 103/mm3) without
Access this article online
overt bleeding complications.
Quick Response Code: Website:
www.atmph.org
Exclusion criteria: Following cases were excluded from
the study:
DOI: a. Patients of dengue fever with platelet counts
10.4103/1755-6783.102004 < 10 × 103/mm3.
b.
Patients of dengue fever with severe
thrombocytopenia requiring platelet transfusion.
Correspondence:
Prof. Arvind Vaish, B-1230, Indira Nagar, Lucknow – 226 016, Uttar Pradesh, India.
E-mail: vaish12@rediffmail.com

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282 Annals of Tropical Medicine and Public Health | Jul-Aug 2012 | Vol 5 | Issue 4
Vaish, et al.: Vitamin E on thrombocytopenia in dengue fever

c. Patients of dengue fever with overt bleeding counting. Serial monitoring of platelet counts was done
complications. on days 1, 4, and 7 in all the cases.
d. Patients of dengue fever with history of platelet
transfusion during present illness. The patients were closely observed for any bleeding
e. Patients of dengue fever on medications known to manifestations or any side effects to the treatment.
cause thrombocytopenia /interfere with platelet Patients requiring platelet transfusion after enrollment
functions in the study were given platelets and thereafter the
f. Patients of dengue fever with family history of study was terminated in them and no further platelet
bleeding diathesis estimations were done in these cases.
g. Seriously ill patients with dengue fever.
The statistical analysis was performed using SPPS
An informed consent was obtained in all the cases
version 11.0 software. Mean platelet counts of the two
and patients unwilling to participate in the study were
groups measured on days 0, 1, 4, and 7 were compared
excluded.
by Mann-Whitney U test, while discrete (categorical)
observations were compared by Pearson’s Chi-square
Evaluation test. The descriptive values below 5% (P < 0.05) were
Detailed history regarding nature of complaints, considered statistically significant.
duration, bleeding manifestations, recent drug intake –
nature and duration, any other treatment including
platelet transfusion during present illness, previous Table 1: Baseline parameters of patients with dengue
bleeding manifestation, and family history of bleeding fever in both the groups
disorder were inquired in each case. Group I Group II
Number of patients (n) 31 28
Mean age ± SD (years) 28.65 ± 12.33 31.67 ± 11.34
Investigations
Age range
Following investigations were carried out in the cases:
<20 years 8 7
1. Hemogram including platelet counts. 20–40 years 14 16
2. NS1 antigen (Dengue NS1 Antigen Microlisa kit 40–60 years 6 6
marketed by J.Mitra and Co., India.) >60 years 2 1
3. IgM Dengue antibodies (IVD IgM dengue kit Male: Female 7.5:1 5:1
marketed by IVD Research Inc.,USA) Duration of complaints 5.76 ± 3.2 days 6.2 ± 3.6 days
4. Liver function tests. Laboratory findings (Mean ± SEM)
5. Blood urea and serum creatinine. Mean hemoglobin (gm/dl) 12.25 ± 2.65 11.4 ± 1.78
6. Bleeding time/clotting time. Mean TLC (cells/mm3) 7152 ± 1310 6693 ± 2738.56
7. Prothrombin time/prothrombin concentration. Mean platelet count (cells/mm3) 28.39 ± 1.6 x 103 27.64 ± 1.65 x 103
NS1Antigen (n) 14 (45.16%) 11 (39.29%)
Categorization of cases: Cases were randomly IgM Dengue antibody (n) 17 (54.84%) 17 (60.71%)
categorized into two groups. Drug history
Aspirin Nil Nil
Group I: This received vitamin E 400 mg (Evion, NSAID Nil Nil
Merck) once daily in addition to standard treatment Paracetamol Nil Nil
given in Group II. Liver function test
Serum bilirubin(mg/dl) 1.69 ± 1.30 1.36 ± 1.18
Group II: This received standard treatment comprising SGOT(IU/L) 188.5 ± 115.12 159.5 ± 100.11
of intravenous fluids, antacids, and close monitoring. SGPT(IU/L) 155.5 ± 133.27 142.2 ± 124.87
SALP(IU/L) 446 ± 230 525 ± 324
Patients were followed up on the above treatment for Blood urea (mg/dl) 31.6 ± 10.59 30 ± 16.87
7 days. Compliance to the drugs was assessed by pill Serum creatinine (ng/ml) 0.97 ± 0.40 0.92 ± 0.54

Table 2: Mean platelet counts in Groups I and II measured serially in our cases with dengue fever
Platelet counts (Mean ± SEM)
Day 0 Day 1 Day 4 Day 7
Group I (n = 31) 28.39 ± 1.61 × 103 51.87 ± 3.11 × 103 122.19 ± 9.98 × 103 217.35 ± 17.17 × 103
Group II (n = 28) 27.64 ± 1.65 × 103 58.61 ± 5.04 × 103 92.57 ± 7.93 × 103 146.78 ± 13.11 × 103
P value P = 0.7384 P = 0.3545 P = 0.0436 P = 0.0030

Annals of Tropical Medicine and Public Health | Jul-Aug 2012 | Vol 5 | Issue 4 283
Vaish, et al.: Vitamin E on thrombocytopenia in dengue fever

c. Patients of dengue fever with overt bleeding counting. Serial monitoring of platelet counts was done
complications. on days 1, 4, and 7 in all the cases.
d. Patients of dengue fever with history of platelet
transfusion during present illness. The patients were closely observed for any bleeding
e. Patients of dengue fever on medications known to manifestations or any side effects to the treatment.
cause thrombocytopenia /interfere with platelet Patients requiring platelet transfusion after enrollment
functions in the study were given platelets and thereafter the
f. Patients of dengue fever with family history of study was terminated in them and no further platelet
bleeding diathesis estimations were done in these cases.
g. Seriously ill patients with dengue fever.
The statistical analysis was performed using SPPS
An informed consent was obtained in all the cases
version 11.0 software. Mean platelet counts of the two
and patients unwilling to participate in the study were
groups measured on days 0, 1, 4, and 7 were compared
excluded.
by Mann-Whitney U test, while discrete (categorical)
observations were compared by Pearson’s Chi-square
Evaluation test. The descriptive values below 5% (P < 0.05) were
Detailed history regarding nature of complaints, considered statistically significant.
duration, bleeding manifestations, recent drug intake –
nature and duration, any other treatment including
platelet transfusion during present illness, previous Table 1: Baseline parameters of patients with dengue
bleeding manifestation, and family history of bleeding fever in both the groups
disorder were inquired in each case. Group I Group II
Number of patients (n) 31 28
Mean age ± SD (years) 28.65 ± 12.33 31.67 ± 11.34
Investigations
Age range
Following investigations were carried out in the cases:
<20 years 8 7
1. Hemogram including platelet counts. 20–40 years 14 16
2. NS1 antigen (Dengue NS1 Antigen Microlisa kit 40–60 years 6 6
marketed by J.Mitra and Co., India.) >60 years 2 1
3. IgM Dengue antibodies (IVD IgM dengue kit Male: Female 7.5:1 5:1
marketed by IVD Research Inc.,USA) Duration of complaints 5.76 ± 3.2 days 6.2 ± 3.6 days
4. Liver function tests. Laboratory findings (Mean ± SEM)
5. Blood urea and serum creatinine. Mean hemoglobin (gm/dl) 12.25 ± 2.65 11.4 ± 1.78
6. Bleeding time/clotting time. Mean TLC (cells/mm3) 7152 ± 1310 6693 ± 2738.56
7. Prothrombin time/prothrombin concentration. Mean platelet count (cells/mm3) 28.39 ± 1.6 x 103 27.64 ± 1.65 x 103
NS1Antigen (n) 14 (45.16%) 11 (39.29%)
Categorization of cases: Cases were randomly IgM Dengue antibody (n) 17 (54.84%) 17 (60.71%)
categorized into two groups. Drug history
Aspirin Nil Nil
Group I: This received vitamin E 400 mg (Evion, NSAID Nil Nil
Merck) once daily in addition to standard treatment Paracetamol Nil Nil
given in Group II. Liver function test
Serum bilirubin(mg/dl) 1.69 ± 1.30 1.36 ± 1.18
Group II: This received standard treatment comprising SGOT(IU/L) 188.5 ± 115.12 159.5 ± 100.11
of intravenous fluids, antacids, and close monitoring. SGPT(IU/L) 155.5 ± 133.27 142.2 ± 124.87
SALP(IU/L) 446 ± 230 525 ± 324
Patients were followed up on the above treatment for Blood urea (mg/dl) 31.6 ± 10.59 30 ± 16.87
7 days. Compliance to the drugs was assessed by pill Serum creatinine (ng/ml) 0.97 ± 0.40 0.92 ± 0.54

Table 2: Mean platelet counts in Groups I and II measured serially in our cases with dengue fever
Platelet counts (Mean ± SEM)
Day 0 Day 1 Day 4 Day 7
Group I (n = 31) 28.39 ± 1.61 × 103 51.87 ± 3.11 × 103 122.19 ± 9.98 × 103 217.35 ± 17.17 × 103
Group II (n = 28) 27.64 ± 1.65 × 103 58.61 ± 5.04 × 103 92.57 ± 7.93 × 103 146.78 ± 13.11 × 103
P value P = 0.7384 P = 0.3545 P = 0.0436 P = 0.0030

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Vaish, et al.: Vitamin E on thrombocytopenia in dengue fever

Results out of 33 (6.06%)] as compared to group II [5 out of 33


(15.15%)] also required platelet transfusion during the
We enrolled 66 patients in our study (33 patients in course of the study [Table 4]. The findings in individual
each group). The baseline parameters and findings on cases are depicted graphically in Figures 1 and 2.
initial investigations in these patients are summarized
in Table 1. Of these, 7 patients (group I - 2 and Discussion
group II - 5) developed severe thrombocytopenia
(platelet counts < 10 × 103/mm3) requiring platelet The greatest danger of dengue fever is from the ensuing
transfusion and thereafter the study was terminated in thrombocytopenia with its attendant consequences.
these cases. Remaining 59 patients (group I - 31 and Except for platelet transfusion there is as yet no
group II - 28) were followed for 7 days. satisfactory treatment for the dengue virus induced
thrombocytopenia.[7]
The mean platelet counts during follow-up in the
two groups are summarized in Table 2. At baseline
The pathogenesis of thrombocytopenia in dengue fever
(day 0), there was no significant difference in the mean
is also not precisely defined.[8] There is some evidence
platelet counts in the two groups. On day 1, the mean
that increased oxidative stress may be causative but is
platelet counts were higher but there was no significant
yet unproven.[3,4] If this were so, vitamin E, a potent
difference between the two groups (P  = 0.3545). On
antioxidant, should be helpful in these cases and this
days 4 and 7, the mean platelet counts in group I
cases were 122.19 × 103/mm3 and 217.35 × 103/ mm3, was the basis for the present study.
respectively, which were significantly higher than
the mean platelet counts on these days in group II Our findings indicate that with passage of time, the
(92.57 × 103/mm3 and 146.78 × 103/mm3, respectively) platelet counts increased in both the groups, the
[P (day 4) = 0.0436 and P (day 7) = 0.003]. increase was faster and greater in the group I receiving
vitamin E 400 mg/daily with significant differences
The percentage of cases who achieved platelet count being apparent on day 4 and day 7. The proportion
> 100 × 103/mm3 on days 4 and 7 in the two groups of cases achieving platelet counts > 100 × 103/mm3
are shown in Table 3, which was significantly better in was also significantly greater in group I on day 4 as
group I as compared to group II. Less cases in group I [2 compared to the group II and this difference between

Table 3: Number of patients in groups I and II achieving Table 4: Number of patients requiring platelet
platelet counts > 100 × 103/mm on days 4 and 7 transfusion in Groups I and II
Day 4 (%) Day 7 (%) Group I (n = 33) Group II (n = 33)
Group I (n = 31) 20 (64.52)* 28 (90.32)** 2 (6.06%) 5 (15.15%)
Group II (n = 28) 11 (39.28)* 20 (71.43)** P value = 0.1761
*P value = 0.0526. **P value = 0.0628

Figure 1: Graph showing the serial platelet counts in patients in group I Figure 2: Graph showing the serial platelet counts in patients in group II

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Vaish, et al.: Vitamin E on thrombocytopenia in dengue fever

the groups had narrowed by day 7. This indicates that mediacentre/factsheets/fs117/en/index.html. [accessed on 2011
Jun 4].
the platelet counts in the group not receiving vitamin E
2. World Health Organization. Dengue: Guidelines for diagnosis,
(group II) tended to catch up later in the course of the treatment, prevention and control, New Edition, 2009. Available from:
disease due to its self-limited nature. The benefit was http://www.who.int/rpc/guidelines/9789241547871/en/. [accessed on
also evident in the number of cases requiring platelet 2011 Jun 4].
3. Gil L, Martínez G, Tápanes R, Castro O, González D, Bernardo L,
transfusion in the two groups [Table 4].
et al. Oxidative stress in adult dengue patients. Am J Trop Med Hyg
2004;71:652-7.
Conclusion 4. Klassen P, Biesalski HK, Mazariegos M, Solomons NW, Fürst P.
Classic Dengue fever affects levels of circulating antioxidants. Nutrition
2004;20:542-7.
It therefore appears from our study that vitamin E can 5. Sies H, Stahl W. Vitamins E and C, beta-carotene, and other
accelerate the replenishment of the circulation with carotenoids as antioxidants. Am J Clin Nutr 1995;62:1315S-21.
platelets in dengue fever, thereby reducing the risk of 6. Mascio PD, Murphy ME, Sies H. Antioxidant defense systems: the
bleeding, particularly during the initial period when the role of carotenoids, tocopherols, and thiols. Am J Clin Nutr 1991;53:
194S-200.
risk is greatest. As vitamin E is simple, safe to administer, 7. Chairulfatah A, Setiabudi D, Agoes R, Colebunders R.
this would be a valuable effect and there would be no harm Thrombocytopenia and Platelet Transfusions in Dengue Haemorrhagic
in using it in such patients. However, we recommend a Fever and Dengue Shock Syndrome. Dengue Bull 2003;27:138-43.
larger trial for its confirmation. We are not aware of any 8. Lei HY, Huang KJ, Lin YS, Yeh TM, Liu HS, Liu CC. Immunopathogenesis
of Dengue Hemorrhagic Fever. Am J Infect Dis 2008;4:1-9.
similar study done with vitamin E in such cases so far.
Cite this article as: Vaish A, Verma S, Agarwal A, Gupta L, Gutch M.
References Effect of vitamin E on thrombocytopenia in dengue fever. Ann Trop Med
Public Health 2012;5:282-5.
1. World health organization 2009 Factsheet No. 11. Dengue and
Source of Support: Nil, Conflict of Interest: None declared.
dengue haemorrhagic fever. Available from: http://www.who.int/

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