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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 11
| Issue : 4 | Page : 328-332 |
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Role of mean platelet volume and platelet distribution width in assessing the severity of dengue fever: An observational study
Shreya Arora1, Monica Gupta1, Anita Tahlan2, Samiksha Gupta1, Gautam Jesrani1
1 Department of General Medicine, Government Medical College and Hospital, Chandigarh, India
2 Department of Pathology, Government Medical College and Hospital, Chandigarh, India
| Date of Submission | 17-Oct-2022 |
| Date of Acceptance | 02-Jan-2023 |
| Date of Web Publication | 17-Mar-2023 |
Correspondence Address:
Dr. Gautam Jesrani
Department of General Medicine, Level 4, D Block, Government Medical College and Hospital, Sector 32-160 030, Chandigarh
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/jdrntruhs.jdrntruhs_182_22
Background: Platelet count has been widely used to evaluate the severity, guide management and predict outcome in patients with dengue fever. This sole use, however, has prevented the utility of other platelet indices like Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) from being explored.
Objectives: To study the association of MPV and PDW with the disease severity in patients with dengue fever.
Materials and Methods: This prospective observational study was conducted in a tertiary care centre of Northern India for a period of one year. A total of 100 patients with confirmed dengue infection who fulfilled the inclusion criteria were followed from the day of admission to recovery. Clinical and laboratory findings, including platelet parameters were noted. They were classified on the basis of World Health Organization (WHO) 2009 criteria, and MPV and PDW values were correlated in each category. Pearson correlation analysis was performed for correlation identification between platelet indices and disease severity.
Results: 64% patients with dengue fever had a low MPV (<9.0 fl). An increased PDW (>13 fl) was observed in 77% cases. A significant correlation was observed between low MPV and platelet count in severe dengue (P value <0.01). Strongest correlation was observed between low MPV and severe dengue (r value 0.745). No significant correlation was witnessed between PDW and severity of infection.
Conclusion: Mean platelet volume may serve as an additional laboratory marker to predict severe dengue infection, but PDW is inferior in delineating the disease severity.
Keywords: Dengue fever, mean platelet volume, platelet count, platelet distribution width, platelet indices
How to cite this article:
Arora S, Gupta M, Tahlan A, Gupta S, Jesrani G. Role of mean platelet volume and platelet distribution width in assessing the severity of dengue fever: An observational study. J NTR Univ Health Sci 2022;11:328-32 |
How to cite this URL:
Arora S, Gupta M, Tahlan A, Gupta S, Jesrani G. Role of mean platelet volume and platelet distribution width in assessing the severity of dengue fever: An observational study. J NTR Univ Health Sci [serial online] 2022 [cited 2023 Mar 21];11:328-32. Available from: https://www.jdrntruhs.org/text.asp?2022/11/4/328/371755 |
| Introduction | |  |
Dengue fever (DF) is an arboviral disease caused by one of the four serotypes of Dengue virus (DEN 1-4), belonging to the family Flaviviridae. The primary vector for the disease is Aedes aegypti mosquito, which is widely spread in the tropical and subtropical regions. It is an imperative public health challenge globally with more than 2.5 billion people at risk of infection in the tropics and subtropics.[1] Annually, an estimated 390 million (284-528 million) dengue infection occurs in around 129 countries, of which 70% of the burden contributor is in Asia.[1] The disease ranges from a mild subclinical infection to acute febrile illness to full blown shock.
In 2009, the WHO revised the classification of the disease from 1997 dengue case guidelines (dengue fever, dengue hemorrhagic fever and dengue shock syndrome). The current scheme is based on the levels of severity, i.e., dengue without warning signs, dengue with warning signs (abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy, restlessness, hepatomegaly, and increased haematocrit concurrent with a rapid decrease in platelet count) and severe dengue.[2] The modification was done as dengue affects different age groups and a wide geographical area. The course of DF depends on numerous underlying factors such as age, comorbid conditions, infecting serotype and secondary infection with other serotypes/organisms. Of all the clinical features, the disease severity and mortality appear to depend maximum on the occurrence of bleeding manifestations, which can vary from minor petechiae and gum bleeding to life-threatening internal hemorrhage, and such manifestations are assumed as a result of underlying thrombocytopenia.[3] The exact mechanisms of thrombocytopenia in DF remain unclear, although many theories have been postulated for it.[4],[5]
The platelet count has been used to predict the course of DF in a patient since long, so as to predict the likelihood of bleeding, severity of illness and prognosticate patient recovery. Nevertheless, there are various drawbacks associated with this parameter. Foremost, apart from the platelet count, effective hemostasis also depends on the platelet activity. Relying solely on platelet count to predict bleeding outcomes can be premature. Secondly, analytical errors by the automated analyzers result in falsely low platelet counts in routine practice, due to either giant platelets or platelet aggregates in the blood. Such analytical errors are common during stages of inflammation. Furthermore, an artefactual rise in automated platelet count due to bacterial overgrowth in the sample may mask underlying thrombocytopenia, and lead to inaccurate results.[6] This may lead to unnecessary platelet transfusions, which have their own associated risks and cost implications.
The exclusive dependence on platelet count as a management criterion for DF has prevented the potential efficacy of other indices like Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) from being explored and recognized. The MPV is a measure of platelet size, and can be used as a surrogate marker for bone marrow activity, while PDW measures the variability in the size of platelets. These indices are calculated and given by every 3-part differential cell counter, but are often not reported, possibly because their utility in clinical practice has not been well-established. Based on these concepts, the platelet indices and the lack of substantial evidence in their utility, this study was formulated to recognize whether these indices can be used as better alternatives or as adjuncts to platelet count in the evaluation of severity in dengue patients.
| Objective | | |
To study the association of MPV and PDW with the disease severity in patients with dengue fever.
| Materials and Methods | | |
Design and study population
This observational study was done prospectively in a tertiary health care center of North India during the recent dengue outbreak in 2020-2021. All patients aged 12 years and above, whose clinical presentation was compatible with that of dengue were screened. A presumptive diagnosis of dengue infection was made in the setting of the typical symptoms (fever, nausea/vomiting, rash, headache, eye/muscle or joint pain, leucopenia and positive tourniquet test), which was subsequently confirmed by specific laboratory tests (demonstration of dengue NS1 antigen or IgM antibody). Patients suffering with pre-existing chronic disease which may interfere with the assessment of complications of DF, or having concurrent infections were excluded. Also, those who had received prophylactic blood transfusions before the emergence of bleeding manifestations were also excluded.
Ethical approval and consent to participate
The study was approved form institutional review board (vide number RC-13-Mar-19). Informed consent after explaining the study and objectives was obtained from every individual, and further assessment was done only after obtaining positive written consent. The study participants were assured that the confidentiality of their personal data would be maintained.
Sample collection and follow up
Cases with confirmed dengue infection were followed from the day of admission till they either recovered clinically and were discharged or suffered from complications. Demographic details, clinical features and warning signs were noted. Laboratory findings including platelet parameters (count, MPV and PDW) were recorded using BC 3000 plus Mindray Automated Hematology Analyzer on venous samples collected in ethylene-diamine tetra-acetic acid (EDTA) vials. The samples were analyzed within one hour of sample collection.
The patients were divided into 3 categories (classical dengue, dengue with warning signs and severe dengue) based on their clinical progression. The indices were compared between these 3 groups to look for any association with the severity of the disease.
Statistical analysis
Data was collected and entered into Microsoft Office Excel Sheet 2019. Statistical analysis was performed using the latest SPSS version 28 software, including descriptive analysis. Pearson's correlation analysis was performed on the 3 platelet indices, and later with risk and severity categories of patients. Any P value of <0.05 was considered significant.
| Result | | |
Description of study population
A total of 100 confirmed cases of DF were included in the study. Among these, 38% were females and 62% were males. The age-related demographics demonstrated maximum number (52) of patients in the age group of 26-50 years. 24 patients belonged to <25 years of age, 21 in the age group of 51-75 years and 3 patients were >75 years of age. Serological parameters showed that 63 patients were positive for dengue NS-1 antigen, 35 patients were positive for dengue IgM by ELISA and 2 patients were positive for both NS1 and IgM.
MPV and RDW values and its correlation with disease severity
Among the patients who developed severe dengue (characterized by the presence of shock and respiratory distress), a low MPV (<9 fl) was present in all 4 cases (100%). In the 19 patients that developed dengue with warning signs (manifested by abdominal pain, clinical fluid accumulation, mucosal bleeding, and lethargy), a low MPV was present in 14 cases (~74%). In the remaining, 77 cases of dengue with no warning signs, a low MPV was seen in 46 cases (60%). The mean values for MPV and PDW of the 3 groups are presented in [Table 1].
A significant positive correlation (r = 0.587, P < 0.01) was observed between rising and falling trends of platelet counts with MPV for the overall sample [Figure 1] as well as for all the 3 risk groups individually [Table 2]. The strongest correlation has been noted for the group with severe dengue with a correlation coefficient of 0.745 (P < 0.01). | Table 2: Pearson Correlation Analysis between Platelet Count, MPV and PDW in the 3 Categories Based on Severity of the Disease
Click here to view |
On the other hand, a high PDW (>13 fl) was seen in 77% of all the cases: 100% of patients (n = 4) with severe dengue, 78% of patients (n = 15) with dengue with warning signs, and 75% of patients (n = 58) with dengue without warning signs. A statistically significant correlation was not observed between platelet count and the PDW [Table 2].
| Discussion | | |
Dengue infection is associated with an increase in the vascular permeability and thrombocytopenia. The latter is also recognized by the WHO as a marker of clinical severity. The exact cause of thrombocytopenia in DF has not been elucidated. Possible pathogenesis includes direct suppression of the bone marrow by the virus, anti-dengue antibody mediated damage, peripheral consumption of platelets due to high levels of platelet-activating factor, isolated viral replication in the platelet or abnormal pooling of blood.[4] Studies have shown that DF is characterized by increased platelet activation (as evidenced by increased expression of P- selectin on the platelet surface), increased apoptosis (as shown by increased phosphatidylserine levels) and complement mediated destruction; all of which account for thrombocytopenia.[5]
PDW is also measure of platelet activation and heterogeneity. In our study, an increased PDW was seen in 77% of the cases. A study by Xu et al.[7] postulated that a higher PDW in hypo-productive thrombocytopenia could be due to significant dysplasia of hematopoiesis in the bone marrow. Any significant correlation was not observed between the PDW and platelet count or disease severity in this study. Similar to this, a recent literature by Khatri S et al.[8] on 106 patients demonstrated no significant changes in PDW, MPV and plateletcrit in DF with thrombocytopenia. Although, severe and bleeding manifestations were few in included patients.
Similar to our data, a case-control research by Bashir et al.[9] on 334 patients with DF revealed lower levels of MPV and platelet count with increased value of PDW. It also exhibited that MPV <9 fl and PDW >13 fl had very high sensitivity for DF. A considerable sensitivity and specificity was recorded by Hardeva et al.[10] for low platelet count and MPV values, and high PDW, which can be used as a predictor of the severity of dengue infection. Krishnamurthy et al.[11] and Kumar et al.[12] also observed similar findings in their respective research.
It has been well established that a low platelet count is associated with increased risk of developing bleeding and other complications.[13] This is also in accordance with our observations. However, having a combination of markers for relation is more efficient than relying on a single parameter alone. Platelet activation leads to a change in shape from biconcave to spheroid and causes the formation of pseudopodia, which affects the values of MPV and PDW.[14],[15] Observing MPV and platelet count trends together can help interpret the major contributory cause of thrombocytopenia in a patient and thus, accordingly aid in assessing the need for transfusion. Plateletcrit is identical to hematocrit, which incorporates MPV and platelet count, and can predict the requirement of platelet transfusion.[14] In a research on MPV and plateletcrit, it was observed that low MPV was associated with high chances of bleeding and low plateletcrit value can identify the need of platelet transfusion.[16]
An increasing MPV suggests a rapid marrow response (a left shift) with the release of newly synthesized, large platelets that increase the overall MPV.[17] In this scenario, the low platelet count is largely due to increased peripheral destruction. The combined presence of low platelet count and high MPV represents adequate marrow functioning and platelet recovery.[14] A wait-full watch may suffice in such a case, hence averting the need for transfusion.[18]
In our study, we concluded that low MPV with thrombocytopenia was associated with an increased severity of infection and bleeding tendencies. In our opinion, serially observing the trends of platelet count and MPV in a dengue patient can help guide further management and prevent redundant transfusions. PDW is increased in dengue infection, although its correlation with the severity of the disease was not established to be clinically significant.
Assessment of platelet transfusion requirement was not assessed in this study due to COVID-19 pandemic, which is one limitation of the research. Additionally, a large number of participants had severe DF, which led to low MPV values, and relationship with platelet transfusion requirement could not be assessed. Studies on a larger scale are required to determine the cut-off values of MPV that would help predict bleeding tendencies and guide protocols for transfusions.
| Conclusion | | |
Platelet indices are affected in DF. Our study suggests that MPV could be used as a predictor of severe dengue and development of bleeding manifestations. A rising trend in MPV can point towards possible increased regenerative capacity and recovery, thereby alleviating the need for platelet transfusions and reduction in the overall dengue expense burden significantly. On the other hand, PDW has relatively inferior correlation with disease severity.
Consent to participate
The participants, who gave written informed consent after explaining the study and objectives, were included in this study and all of the participants were assured that confidentiality of their personal data would be maintained.
Ethical approval
The study was approved form institutional research/ethics committee vide number RC-13-Mar-19.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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| 4. | De Azeredo EL, Monteiro RQ, de-Oliveira Pinto LM. Thrombocytopenia in dengue: Interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators. Mediators Inflamm 2015;2015:313842. doi: 10.1155/2015/313842. |
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| 10. | Hardeva RN, Shyam LM, Sahil P, Gupta BK. Evaluation of platelet indices in patients with dengue infections. Int J Sci Res 2016;5:78-81. |
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| 13. | Jayashree K, Manasa GC, Pallavi P, Manjunath GV. Evaluation of platelets as predictive parameters in dengue Fever. Indian J Hematol Blood Transfus 2011;27:127-30. |
| 14. | Kantharaj A. Role of red cell and platelet indices as a predictive tool for transfusions in dengue. Glob J Transfus Med 2018;3:103-8. [Full text] |
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| 16. | R Mohr, U Martinowitz, M Golan, L Ayala, D A Goor, B Ramot. Platelet size and mass as an indicator for platelet transfusion after cardiopulmonary bypass. Circulation 1986;74:153-8. |
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[Figure 1]
[Table 1], [Table 2]
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