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 × 10 3 /mm 3 and 100 × 10 3 /mm 3 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 × 10 3 /mm 3 and group II – 27.64 ± 1.65 × 10 3 /mm 3 ) (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 × 10 3 /mm 3 ; CI 95% -102.63 × 10 3 /mm 3 – 141.76 × 10 3 /mm 3 ) than in group II (Mean – 92.57 ± 7.93 × 10 3 /mm 3 ; CI 95% – 77.03 × 10 3 /mm 3 – 108.11 × 10 3 /mm 3 ) (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.
Keywords: Bleeding, dengue fever, thrombocytopenia, vitamin E
|How to cite this article:
Vaish A, Verma S, Agarwal A, Gupta L, Gutch M. Effect of vitamin E on thrombocytopenia in dengue fever. Ann Trop Med Public Health 2012;5:282-5
|How to cite this URL:
Vaish A, Verma S, Agarwal A, Gupta L, Gutch M. Effect of vitamin E on thrombocytopenia in dengue fever. Ann Trop Med Public Health [serial online] 2012 [cited 2020 Aug 11];5:282-5. Available from: https://www.atmph.org/text.asp?2012/5/4/282/102004
In recent years, dengue fever has become a worldwide public health concern. In India, epidemics are becoming more frequent and are exhausting the limited public health resources. Untreated, mortality of dengue fever can be as high as 20%, whereas if recognized earlier and managed properly mortality is less than 1%.  The major threat of dengue fever is from thrombocytopenia and consequently from the bleeding manifestations. There is as yet no satisfactory treatment for thrombocytopenia in these cases.  The pathogenesis of thrombocytopenia in dengue fever is not clear but increased oxidative stress may have a role. , Vitamin E which has antioxidant and free-radical scavenging properties and may therefore help in these cases. , Hence, in the present study, we have evaluated the effect of vitamin E on thrombocytopenia in the cases of dengue fever.
|Materials and Methods|
Prospective randomized open blinded evaluation (PROBE) design.
Inclusion criteria: Patient of dengue fever (as per WHO criteria  ) with thrombocytopenia (platelet count between 10 × 10 3 /mm 3 and 100 × 10 3 /mm 3 ) without overt bleeding complications.
Exclusion criteria: Following cases were excluded from the study:
- Patients of dengue fever with platelet counts < 10 × 10 3 /mm 3 .
- Patients of dengue fever with severe thrombocytopenia requiring platelet transfusion.
- Patients of dengue fever with overt bleeding complications.
- Patients of dengue fever with history of platelet transfusion during present illness.
- Patients of dengue fever on medications known to cause thrombocytopenia /interfere with platelet functions
- Patients of dengue fever with family history of bleeding diathesis
- Seriously ill patients with dengue fever.
An informed consent was obtained in all the cases and patients unwilling to participate in the study were excluded.
Detailed history regarding nature of complaints, duration, bleeding manifestations, recent drug intake – nature and duration, any other treatment including platelet transfusion during present illness, previous bleeding manifestation, and family history of bleeding disorder were inquired in each case.
Following investigations were carried out in the cases:
- Hemogram including platelet counts.
- NS1 antigen (Dengue NS1 Antigen Microlisa kit marketed by J.Mitra and Co., India.)
- IgM Dengue antibodies (IVD IgM dengue kit marketed by IVD Research Inc.,USA)
- Liver function tests.
- Blood urea and serum creatinine.
- Bleeding time/clotting time.
- Prothrombin time/prothrombin concentration.
Categorization of cases: Cases were randomly categorized into two groups.
Group I: This received vitamin E 400 mg (Evion, Merck) once daily in addition to standard treatment given in Group II.
Group II: This received standard treatment comprising of intravenous fluids, antacids, and close monitoring.
Patients were followed up on the above treatment for 7 days. Compliance to the drugs was assessed by pill counting. Serial monitoring of platelet counts was done on days 1, 4, and 7 in all the cases.
The patients were closely observed for any bleeding manifestations or any side effects to the treatment. Patients requiring platelet transfusion after enrollment in the study were given platelets and thereafter the study was terminated in them and no further platelet estimations were done in these cases.
The statistical analysis was performed using SPPS version 11.0 software. Mean platelet counts of the two groups measured on days 0, 1, 4, and 7 were compared by Mann-Whitney U test, while discrete (categorical) observations were compared by Pearson’s Chi-square test. The descriptive values below 5% (P < 0.05) were considered statistically significant.
We enrolled 66 patients in our study (33 patients in each group). The baseline parameters and findings on initial investigations in these patients are summarized in [Table 1]. Of these, 7 patients (group I – 2 and group II – 5) developed severe thrombocytopenia (platelet counts < 10 × 10 3 /mm 3 ) requiring platelet transfusion and thereafter the study was terminated in these cases. Remaining 59 patients (group I – 31 and group II – 28) were followed for 7 days.
|Table 1: Baseline parameters of patients with dengue fever in both the groups
Click here to view
The mean platelet counts during follow-up in the two groups are summarized in [Table 2]. At baseline (day 0), there was no significant difference in the mean platelet counts in the two groups. On day 1, the mean platelet counts were higher but there was no significant difference between the two groups (P = 0.3545). On days 4 and 7, the mean platelet counts in group I cases were 122.19 × 10 3 /mm 3 and 217.35 × 10 3 / mm 3 , respectively, which were significantly higher than the mean platelet counts on these days in group II (92.57 × 10 3 /mm 3 and 146.78 × 10 3 /mm 3 , respectively) [P (day 4) = 0.0436 and P (day 7) = 0.003].
|Table 2: Mean platelet counts in Groups I and II measured serially in our cases with dengue fever
Click here to view
The percentage of cases who achieved platelet count > 100 × 10 3 /mm 3 on days 4 and 7 in the two groups are shown in [Table 3], which was significantly better in group I as compared to group II. Less cases in group I [2 out of 33 (6.06%)] as compared to group II [5 out of 33 (15.15%)] also required platelet transfusion during the course of the study [Table 4]. The findings in individual cases are depicted graphically in [Figure 1] and [Figure 2].
|Table 3: Number of patients in groups I and II achieving platelet counts > 100 × 103/mm on days 4 and 7
Click here to view
|Table 4: Number of patients requiring platelet transfusion in Groups I and II
Click here to view
|Figure 1: Graph showing the serial platelet counts in patients in group I
Click here to view
|Figure 2: Graph showing the serial platelet counts in patients in group II
Click here to view
The greatest danger of dengue fever is from the ensuing thrombocytopenia with its attendant consequences. Except for platelet transfusion there is as yet no satisfactory treatment for the dengue virus induced thrombocytopenia. 
The pathogenesis of thrombocytopenia in dengue fever is also not precisely defined.  There is some evidence that increased oxidative stress may be causative but is yet unproven. , If this were so, vitamin E, a potent antioxidant, should be helpful in these cases and this was the basis for the present study.
Our findings indicate that with passage of time, the platelet counts increased in both the groups, the increase was faster and greater in the group I receiving vitamin E 400 mg/daily with significant differences being apparent on day 4 and day 7. The proportion of cases achieving platelet counts > 100 × 10 3 /mm 3 was also significantly greater in group I on day 4 as compared to the group II and this difference between the groups had narrowed by day 7. This indicates that the platelet counts in the group not receiving vitamin E (group II) tended to catch up later in the course of the disease due to its self-limited nature. The benefit was also evident in the number of cases requiring platelet transfusion in the two groups [Table 4].
It therefore appears from our study that vitamin E can accelerate the replenishment of the circulation with platelets in dengue fever, thereby reducing the risk of bleeding, particularly during the initial period when the risk is greatest. As vitamin E is simple, safe to administer, this would be a valuable effect and there would be no harm in using it in such patients. However, we recommend a larger trial for its confirmation. We are not aware of any similar study done with vitamin E in such cases so far.
|1.||World health organization 2009 Factsheet No. 11. Dengue and dengue haemorrhagic fever. Available from: http://www.who.int/mediacentre/factsheets/fs117/en/index.html. [accessed on 2011 Jun 4].|
|2.||World Health Organization. Dengue: Guidelines for diagnosis, treatment, prevention and control, New Edition, 2009. Available from: http://www.who.int/rpc/guidelines/9789241547871/en/. [accessed on 2011 Jun 4].|
|3.||Gil L, Martínez G, Tápanes R, Castro O, González D, Bernardo L, et al. Oxidative stress in adult dengue patients. Am J Trop Med Hyg 2004;71:652-7.|
|4.||Klassen P, Biesalski HK, Mazariegos M, Solomons NW, Fürst P. Classic Dengue fever affects levels of circulating antioxidants. Nutrition 2004;20:542-7.|
|5.||Sies H, Stahl W. Vitamins E and C, beta-carotene, and other carotenoids as antioxidants. Am J Clin Nutr 1995;62:1315S-21.|
|6.||Mascio PD, Murphy ME, Sies H. Antioxidant defense systems: the role of carotenoids, tocopherols, and thiols. Am J Clin Nutr 1991;53:194S-200.|
|7.||Chairulfatah A, Setiabudi D, Agoes R, Colebunders R. Thrombocytopenia and Platelet Transfusions in Dengue Haemorrhagic Fever and Dengue Shock Syndrome. Dengue Bull 2003;27:138-43.|
|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.|
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]