Studying The Individual Role And Interrelationship Between Mean Platelet Volume And Platelet Distribution Width In Predicting The Fall/Rise Of Platelet Count In Dengue

Global Journal of Pathology & Laboratory Medicine
Volume 2, Issue 1, July, 25-36

Unified Citation Journals, Pathology 2023, 2(1) 25-36; https://doi.org/10.52402/Pathology218
ISSN 2754-0952

Author: Dr M Naveen Kumar 1, Dr. Bhargavi 2, Dr. Vinila Belum Reddy 3, Dr S Jayabhaskar Reddy 4, Dr Manimekhala P 5, Dr Vanajakshi S 6, Dr Bala Krishna 7

1) Assistant Professor, Department Of Pathology, AIMSR Hyderabad
2) Intern, Department Of Pathology, AIMSR Hyderabad
3) Associate Professor, Department Of Pathology, AIMSR Hyderabad
4) Professor & Hod, Department Of Pathology, AIMSR Hyderabad
5) Professor Department Of Pathology, AIMSR Hyderabad
6) Assistant Professor, Department Of Pathology, AIMSR Hyderabad
7) Assistant Professor, Department Of Statistics, AIMSR Hyderabad

INTRODUCTION

Dengue, a mosquito borne viral infection, has emerged as a global disease within a short span of thirty years. Aided by the multi-fold increase in human traffic across the continents and oceans, the infection which was restricted to a few tropical countries a century ago, has spread to subtropical and temperate regions(1). 2.5 Billion people around the world live in dengue endemic countries, half of which live in 10 countries of the South-East Asia region. WHO has categorised these countries into A, B and C categories depending on the variable endemicity of dengue infection. Category A signifies hyperendemicity and India falls into this category⁽¹⁾.According to the National Vector Borne Disease Control Programme (NVBDCP), Government of India, a total of 44585 Dengue cases were reported country wide in 2021 (as of September). 7.66% were from the state of Telangana, 50% of which were from the city of Hyderabad alone ⁽²⁾.
Primary infection by any one of the four serotypes DE 1, 2, 3 & 4 of Dengue virus (DENV) does not cause any symptoms in most people ⁽³⁾. It is the secondary infection by a heterologous DENV serotype that is the single most important risk factor for severe disease.  This is due to the phenomenon called “antibody-dependent enhancement” (ADE), resulting in increased viral burden and more severe disease (Dengue haemorrhagic fever/DHF and Dengue shock syndrome/DSS) ⁽⁴⁾.
Thrombocytopenia is the hallmark of Dengue fever, along with leucopoenia ⁽⁵⁾. It occurs due to the combined effect of decreased bone marrow production and increased peripheral destruction of platelets.The decreasing platelet counts have found to predict the severity of the disease⁽¹²⁾. Hence, it is important to study platelets profile and understand its course during the disease.Mean platelet volume (MPV), which is the measure of size of an average platelet, is a marker of platelet production and activation ⁽⁶⁾. A high MPV indicates increased megakaryocytic activity. A low MPV indicates marrow suppression and increased risk of bleeding ⁽⁷⁾. Similarly platelet distribution width (PDW), which is a measure of platelet heterogeneity, is also an indirect marker for platelet activation ⁽⁸⁾. Thus, both, MPV and PDW may help in determining the marrow function as well as platelet activation during the disease progression in Dengue fever and also act as early predictors of imminent platelet fall/rise.
This study will help in advancing the knowledge of pathophysiology of Dengue infection and its spectrum of disorders. By attempting such a study, we are trying to correlate the changes in platelet indices with the variations in platelet count. If a direct correlation is found, it would help in planning the treatment better and save the patient by governing them towards a better prognosis. It simultaneously would forbid unnecessary platelet transfusions, which bleed them financially, and prevent wastage of resources.

REVIEW OF LITERATURE

Dengue virus causes a wide spectrum of disease, ranging from subclinical to severe flu-like disease. Geographical distribution of the disease has significantly augmented with a large number of cases remaining undiagnosed and underreported. Most of the cases tend to come to the physician’s attention in the later stages of the disease, as often patients consult the doctor only when their symptoms begin to worsen.
Platelet counts have no role in determining the need for transfusion in dengue. This is because transfused platelets are as likely to be destroyed by the antibodies as one’s own platelets and hence platelet transfusions have a limited role in the management of dengue ⁽⁹⁾.
Consistent monitoring of the patient’s MPV & PDW values would help in early detection of complications and help in undertaking precautionary measures to prevent further deterioration of the patient. The Mean Platelet Volume and Plateletcrit has positive correlation with low platelet count. Low MPV with low platelet count implies marrow suppression as a mechanism of thrombocytopenia. Whereas Platelet Distribution Width has a negative correlation with low platelet count. High value of Platelet Distribution Width is seen in patients with low platelet count ⁽¹⁰⁾.
High MPV, high PDW, and low plateletcrit are commonly associated with longer duration of therapy and more frequent ICU care requirement ⁽¹¹⁾. Thus, low platelet count, low PCT, low MPV and high PDW may be used as predictor of severity of Dengue infection.
Provision of insight on the relationship between platelet indices and the platelet count of the dengue patients would aid in early recognition of danger signs & symptoms and thus early prediction of the outcome, which further directs approach in therapy.                                                     

AIMS AND OBJECTIVES

The current study focuses on the role of MPV and PDW in determining the course of the disease and in predicting its dreaded complications. Early detection of DHF and DSS would greatly help in better patient management and steering away from the dire consequences. To study the correlation, if any, between MPV, PDW and platelet count in Dengue NS1 positive cases forms the main objective of this study. The aim of the study is to arrive at a “critical value” for MPV and PDW which can confidently predict severe thrombocytopenia in DF.

MATERIALS AND METHODS

The project will be along the lines of an observational study, conducted over a period of two months, during the year 2021, at the Pathology laboratory of Apollo Institute of Medical Sciences and Research, a tertiary care teaching hospital located in Hyderabad.
The current report is a Cross sectional study. Descriptive statistics like mean, Standard Deviation, Percentage will be calculated for all variables and Correlation Coefficient will be calculated between MPV, PDW & Platelet count.
Inclusion criterion for the study will be NS1 positivity in in-patients, as determined by ELISA method on blood samples, who initially present to our out-patient department with symptoms of high-grade fever, retro-orbital headache and rash. All patients who are negative for the non-structural protein 1, irrespective of their symptomatology, are excluded from the study.
Patient’s blood sample will be collected in K3 EDTA tube and the platelet indices will be obtained by using a fully automated 5-part haematology analyser, Mindray 5300. Right from the day of admission to the day of discharge the patient’s platelet indices (MPV & PDW) and platelet count will be monitored. All the data generated will be documented in a Microsoft Excel Sheet.
The statistical analysis will be performed usingIBM SPSS Version 24. Descriptive statistics like mean, Standard Deviation, percentages will be calculated for all categorical variables. Statistical correlation coefficient will be calculated between the observed MPV, PDW and Platelet count correlation between the observed values will be assessed.

Inclusion Criteria- All seropositive cases of dengue (NS1, IgG and IgM) in all age groups

Exclusion Criteria- Thrombocytopenia resulting from causes other than dengue (seronegative)

OBSERVATIONS & RESULTS

A total of 300 cases were enrolled and investigated. There were 180 patients who are male and 120 patients who are females. There were 54 patients in age below 20 years, 42 patients in 20-30 years, 66 patients 30-40 years, 54 patients 40-50 years, 48 patients in 50-60 years, 36 patients in 60-70 years. Mean age of study group was 37.2 ±8.1 years.
Maximum number of the patients was admitted during the monsoon season of the year.
Fever, headache and generalised body pains were the common chief complaints most of the patients presented. Bleeding manifestations like epistaxis and melena were not so common and were seen only in severe cases.
In the study, 282 patients had fever, 210 patients had myalgia, 228 patients had vomiting and headache each, 168 patients had abdominal pain, 72 patients had skin rash, 16 patients each had petechiae and breathlessness, 48 patients had diarrhea.
Most of the patients (88%) were admitted for a week or less. while the remaining (12%) of the total patients were admitted for more than a week. The latter group of patients experienced platelet counts as low as lesser than 29000 per mm³ of blood. Patients experiencing low/high MPV and low/high PDW values were admitted for longer durations.
A negative correlation coefficient value was observed between platelet count and MPV of patients during the course of their hospital stay. Similarly, a negative correlation coefficient value was observed between the platelet count and PDW of patients on the day with a minimum platelet count

Mean MPV in patients with Dengue fever on Day 1 was 7.42 fl, on Day 2 was 8.1 fl, Day 3 was 8.8 fl, on Day 4 was 10.9 fl, on Day 5 was 11.9 fl. P value was 0.04 indicating statistically significant difference between serial values.
Mean PDW in patients with Dengue fever on Day 1 was 12.20%, on Day 2 was 13.10%, Day 3 was 13.90%, on Day 4 was 15.60%, on Day 5 was 17.60%. P value was 0.05 indicating statistically significant difference between serial values.
Mean platelet count in patients with Dengue fever on Day 1 was 95000, on Day 2 was 86,000, Day 3 was 70,000, on Day 4 was 72,500, on Day 5 was 89,000. P value was 0.01 indicating statistically no significant difference between serial values.
The mean MPV and PDW values corresponding to the day with minimum platelet count were 8.8 & 16.435 respectively. And the mean MPV and PDW values corresponding to the day before the day the platelet count started to show a decrease in the patients were 11.90 & 17.91 respectively. Thus, the latter can be considered as ‘critical value’ or ‘value of concern’ beyond which there is a high chance of decrease in the platelet count.

DISCUSSION
Dengue is one of the most common infectious diseases prevailing in India. In spite of the fact that in India dengue was first reported in 1940s, the first case of confirmed dengue infection from Kerala was recorded in 1997 only. Since 2001 occurrence of dengue increased in Kerala and outbreaks were reported repeatedly from most of the central and southern districts ⁽¹²⁾.
Dengue has become a matter of serious concern with the current increasing trends in the number of cases. Severity of the cases increases with an associated decrease in platelet count. Initial decrease in platelet count is associated with an increase in MPV and PDW values indicating compensatory increase in bone marrow activity. Further decrease in platelet count is associated with a decrease in MPV indicating marrow suppression and inefficacious compensatory mechanisms. Timely prediction of decrease in platelet count by carefully observing the trends in MPV and PDW values will help the physicians in taking prompt decisions regarding the further plan of action.

This study is in accordance with our study was:
The incidence of dengue fever was predominant in males in the present study with 60.00% cases which was similar to the study done by  Anker M et al who also found a male predominance⁽¹³⁾. А study conducted by Khаnnа et аl., during аn outbreаk of dengue in Delhi reveаled thаt fever wаs found in аll the pаtients. Other symptoms were heаdаche (73.3 %), retro orbitаl pаin (46.6%), conjunctivаl effusion (66.6 %), аrthrаlgiа (10 %) аnd аbdominаl pаin (100 %). Their study populаtion included 35 mаles аnd 20 femаles. The meаn аge of the pаtients wаs 35.5 yeаrs (rаnge 20 67 yeаrs)⁽¹⁴⁾
Maximum number of cases (44%) were observed in the 20-39 years age group in the present study which was similar to the study conducted by Cecilia D et al who also reported in their 6 year study that the most commonly affected age group was 21-40 years. Afsar N et al also reported 86.7% of cases in their study to be under 30 years of age ^{(15) (16)}.
А study wаs conducted during а lаrge urbаn epidemic of dengue fever in Kollаm city of Kerаlа in by Dаniel et аl., (2005).The clinicаl mаnifestаtions found were fever (96.8 %), heаdаche (77.2 %) sore throаt (5.2 %), diаrrheа (15.2 %), аbdominаl pаin (62.4 %), skin rаshes (13.2 %) аnd pruritis (10.4 %). The study populаtion consisted of 130 mаles аnd 120 femаles. The pаtients meаn аge wаs 12.6 ± 20 аnd the meаn durаtion of symptoms wаs 6 dаys ⁽¹⁷⁾.
A similar study Singh et аl., (2005) found thаt during аn outbreаk of dengue Fever wаs presented in аll the febrile cаses with аn аverаge durаtion of fever being 4.5 ± 1.2 dаys. Other symptoms include heаdаche (61.6 %), bаckаche (57.8 %), vomiting (50.8 %), аbdominаl pаin (21 %), hаemorrhаgic mаnifestаtion in the form of а positive tourniquet test (21 %), gum bleeding аnd epitаxis (40 %), skin rаshes (20 %) аnd melena (14 %) ⁽¹⁸⁾.
Manish et al in their study, (7%) showed feаtures of DF with moderаte аnd severe thrombocytopeniа while only 3 cаses (2.85%) despite treаtment succumbed with further fаll in their plаtelet counts which is significаnt (P < 0.01). Thus, there wаs а significаnt аssociаtion noted between the clinicаl improvement or deteriorаtion of DF cаses аnd their plаtelet counts (P < 0.05) ⁽¹⁹⁾.
Study by Nаbilа et аl observed thаt meаn plаtelet volume wаs found to be significаntly higher in dengue cаses when compаred to controls. MPV wаs аlso noted to be significаntly higher in pаtients with plаtelet count below the normаl biologicаl reference rаnge of 1.5 lаkhs , when compаred to dengue pаtients with normаl plаtelet counts. Study concluded, high MPV indicаtes plаtelet аctivаtion аnd mаy be used аs аn initiаl mаrker to suspect dengue fever in а cаse of thrombocytopeniа ⁽²⁰⁾.
Mitrakul et al observed that platelet count in DHF/DF showed a significant decrease on the 4th day of the illness. In fact, previous studies reported DHF in adults without shock, in which platelet counts mildly to moderately decreased on the 3rd day until the 7th day of illness and reached normal levels on the 8th or 9th day ⁽²¹⁾
In the study by Manoharan A et al, observed that MPV was found to be high in patients with bleeding manifestations which was correlating with our study ⁽²²⁾.
Afsar N et al found a statistically significant p value in their study of MPV which was concurrent with present study. Increased platelet volume increases platelet adhesion, aggregation and synthesis of thromboxanes which can lead to complications like disseminated intravascular coagulation ⁽²³⁾.
A statistically significant p value of 0.05 was obtained for MPV and 0.04 for plateletcrit in the present study which was similar to the observation made by Nehara HR et al who also found a significant positive correlation. (p value<0.0001) ⁽²⁴⁾.
Since bone marrow activity and peripheral destruction of cells also play a major role in the pathogenesis of platelet count or any other blood cell count (that is, Red Blood Cells or White Blood Cells), definite perception of bone marrow mass corresponding to various blood cell indices and preliminary detection of alterations in survival time of blood cells during the disease progression would assist in better prognosis and form the topics of interest for future studies.

CONCLUSION
Fever and myalgia are commonest symptom generally observed in most of the patients. With the decrease in platelet count, the MPV & PDW values showed a gradual increase. Thus indicating a negative correlation between both the platelet count & MPV and platelet count & PDW. Preliminary identification of this increase/decrease would help in early assembling of any needed resources or even prevent any dreadful complications.  However a combination of clinical symptoms and hematological tests like Platelet count, MPV & PDW may help to establish a diagnostic algorithm that can be used to distinguish dengue patients with poor prognosis.

SUMMARY

Present Study was conducted at Dept. of Pathology,  The Apollo Institute of Medical Sciences and Research Hyderabad on sample size of 300 patients between July 2020 to August 2021.
Study focuses on the role of MPV and PDW in determining the course of the disease and in predicting its dreaded complications. A total of 300 cases were enrolled and investigated. There were 180 patients who are male and 120 patients who are females. There were 54 patients in age below 20 years, 42 patients in 20-30 years, 66 patients 30-40 years, 54 patients 40-50 years, 48 patients in 50-60 years, 36 patients in 60-70 years. Mean age of study group was 37.2 ±8.1 years.
Maximum numbers of the patients were admitted during the monsoon season of the year. In the study, 282 patients had fever, 210 patients had myalgia, 228 patients had vomiting and headache each, 168 patients had abdominal pain,72 patients had skin rash, 16 patients each had petechiae and breathlessness, 48 patients had diarrhea. Most of the patients (88%) were admitted for a week or less. while the remaining (12%) of the total patients were admitted for more than a week. The latter group of patients experienced platelet counts as low as lesser than 29000 per mm³ of blood. Patients experiencing low/high MPV and low/high PDW values were admitted for longer durations.

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To citation of this article: Dr M Naveen Kumar 1, Dr. Bhargavi 2, Dr. Vinila Belum Reddy 3, Dr S Jayabhaskar Reddy 4, Dr Manimekhala P 5, Dr Vanajakshi S 6, Dr Bala Krishna 7, Studying The Individual Role And Interrelationship Between Mean Platelet Volume And Platelet Distribution Width In Predicting The Fall/Rise Of Platelet Count In Dengue, Global Journal of Pathology & Laboratory Medicine