Exploring the Relationship between the Platelet Indices and Psychosocial Morbidity in Elderly Patients at a Rural Medical College Hospital

Background: The platelet indices like mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) are a laboratory marker associated with platelet function and activity. We have tried to correlate and compare all these indices in elderly patients as far as psychosocial morbidity like cognition, frailty and depression are concerned. Methods: This was a prospective observational study and it comprised 1000 consecutive elderly patients admitted for routine check-up in medicine department. Blood samples were taken to measure platelet indices like MPV, PDW and PCT. Cognition, frailty and depression were assessed by the Mini mental state examination, frail non disabled questionnaire and Geriatric Depression scale respectively. Result: Patients with normal and high platelet count had a depression score of more than 5. [(p=0.0001, r=0.705)  2=811.21, p=0.0031,S]. In the group of low platelet count, 50.58% patients were robust, 49.42% patients were frail (r=0.792, p=0.0001). Among normal platelet count group, 92.75% were frail (r=0.337, p=0.0001). In high platelet count group, 13.40% were robust, 71.30% frail and 15.30% were disable (r=0.781,  2=652.91; p<0.0001, S). In high platelet count group 81.01% had MMSE score ≤23, (r=-0.440,  2=754.72, p=0.0001, S). 79.25% patients having high PCT had MMSE score ≤23, (r=-0.528,  2=737.28, p=0.0001, S). Conclusion: Platelet indices could be considered meaningful laboratory markers for the risk of psychosocial


Introduction
Ageing is a normal, progressive and irreversible process which affects every individual, family, community and society. Government of India under National Policy on Older Persons has defined 'senior citizen' or 'elderly' as a person who is of age 60 years or above in 1999. In our country total population of elderly is 10 crore, forming 10% of total population and it is estimated to reach up to 15crore by 2020 [1]. Among them at least 50% have chronic diseases thus posing a greater responsibility on the health services where there is a greater strain on available health infrastructure and financial constraints [2]. Aging is a process of deterioration in the functional capacity of an individual that results from structural changes, with advancement of age leading to an increased risk of functional dependence, hospitalization, and mortality [3][4][5].
Therefore, many recent studies have investigated the usefulness of various parameters of automated blood cell counters as biomarkers for adverse clinical outcomes in the elderly. Among them is total leucocytes and some subpopulations of leucocytes which is associated with frailty, red blood cell distribution width seems to be a good indicator of morbidity, and mean platelet volume as markers for cardiovascular disease and its risk factors like hypertension and diabetes [6][7][8][9][10][11][12]. The platelet indices like mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) values exhibited significant variability. There is evidence that Depression is associated with platelet activation, it also became apparent that the selective serotonin reuptake inhibitor (SSRIs) in general and sertraline in particular affect platelet function. SSRIs block reuptake of serotonin not only in nerve cells but also in platelets as well [13,14].
Common psychosocial problems include impaired memory and intelligence, anxiety, depression, frailty, dependency and dissatisfaction with family members, earning and occupation. There is limited knowledge of the usefulness of platelet indices as markers for psychosocial morbidity like depression, frailty, and cognition in the elderly. Research is needed to identify risk factors at a stage of age-related decline that would be amenable to preventive interventions. To address this issue, we have tried to analyse the association of the following platelet indices as Platelet count (PLT), platelet distribution width (PDW), MPV, and platelet crit with psychosocial morbidity as a potential biomarkers.

Material and Method
This prospective observational study was conducted in rural medical hospital at Wardha city, the state of Maharashtra from August 2016 to July 2017. All consecutive patients above the age of 60 years admitted in our hospital were enrolled for the study, after taking approval from the institutional ethics committee. In our hospital there is Adhar scheme which provides free of cost screening and treatment for the patients having average daily admission of 15 to 20 patients, being most of them elderly. We have enrolled 1200 elderly patients under this scheme who has come for routine checkup. Patients having malignant disease, infection, h/o blood transfusion, myeloproliferative disorder, h/o recent major surgery, h/o intake of anti-platelet drugs, h/o chemotherapy/radiotherapy and critically ill were excluded from the study. Total 200 patients were excluded from the study and 1000 were enrolled ( Figure 1). Review was done regarding subject's medical and pharmacological history, a physical examination, and a physical activity questionnaire. The disease status of the patient was based on the explicit diagnosis in the patient's medical history. Patient's physical activity and daily life were evaluated on the basis of their frailty index. The diagnosis of dementia and cognitive impairment was based on MMSE and the criteria of the diagnostic and statistical manual of the mental disorder. Each participant's relatives were provided with information about the purpose and objective of the study and signed informed consent. The Geriatric Depression scale was used to assess the probable depression in our study group. A score of ≥5 on geriatric depression scale was suggestive of probable depression.
The frailty score (FIND-frail non disabled questionnaire) was used for diagnosing the frailty. A patient with score a+b=1 was labelled "ROBUST", a patient with score c+d+e=1 was labelled "FRAIL" and patient with a score a+b+c+d+e=0 was labelled as "DISABLED". MMSE (mini mental state examination) questionnaire was used for diagnosing cognitive impairment. A score of ≤23 was suggestive of cognitive impairment.

Blood collection
Blood samples were obtained by venupuncture for biochemical analysis. Following platelet indices had been measured using automated hematology analyzer in the central laboratory of the hospital-platelet count, mean platelet volume and platelet distribution width and platelet crit.

B.
Plateletcrit: It is a measure of total platelet mass (0.150 to 0.500%).

C.
Mean platelet volume: It is the average size of platelets (6.0 to 11.0/cu micrometer). D. Platelet distribution width: It is the variability in the size of the smallest and the largest platelets (11.0 to 18.0%).

Statistical analysis
Statistical analysis was done by using descriptive and inferential statistics using Chisquare test, Pearsons' correlation coefficient and software used in the analysis were SPSS 20.0 version, Graph Pad Prism 6.0 version and p<0.05 is considered as level of significance.

Result and Observation
In this study we included 1000 patients of whom 601(60.1%) were males and 399(39.9%) were females, mean age was 66.02±5.76years. The mean platelet count was 303210±21296lac/ cu mm, the mean platelet crit 0.29±0.17%, mean platelet volume was 9.25±5.70 per µm 3 , and the mean platelet distribution width 14.18±5.63%. There were 165 males who were chronic smokers and 107 males who were chronic alcoholics.

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Discussion
We have found significant association of the Platelet indices like Platelet count (PLT), platelet distribution width (PDW), MPV, and plateletelcrit (PCT) with psychosocial morbidity like depression, frailty and cognition in elderly subjects. In this study almost all patients with normal (100%) and high (99.6%) platelet count had a depression score of more than 5. [(p=0.0001, r=0.705) 2=811.21,p=0.0031,S]. In a study by Morel et al. [15] similar results was found as the patients with higher platelet count showed more depression, (they used the Montgomery As berg depression rating scale), while in our study geriatric depression scale were taken [15]. The mean age in Morel et al was 42.94±9.99 years. A possible explanation in this context is that depression overlaps with anxiety and panic attack which could lead to sympathetic overdrive; a platelet would respond to adrenalin or noradrenalin released after such stress [15]. In normal platelet count cause of depression is unexplained.
In the group of low platelet count, 50.58% patients were in robust category according to frailty score, 49.42% patients were frail and none were disable, having positive correlation between platelet count and frailty score (r=0.792, p=0.0001). Among normal platelet count group, 92.75% were frail having positive correlation between platelet count and frailty score (r=0.337, p=0.0001). In high platelet count group, 13.40% were robust, 71.30% frail and 15.30% were disable. There was a positive correlation between platelet count and frailty score (r=0.781, 2=652.91; p<0.0001 S).In contrast to our study, Amira A Mahmoud et al. [16] showed non-significant correlation with platelet count and frailty in the age group of 19-70 years (mean age 48.09±18. 3). Phenotypes of frailty used in their study were Cardiovascular health study, and Centre for Epidemiological Studies-Depression. In our study we used FIND questionnaire. In their study 34 (24.2%) patients were robust with mean platelet count of 154.9±42, 22 (15.8%) were prefrail with mean platelet count of 145.7±71.7 and 84(60%) were frail with mean platelet count of 177.4±70.4, which was not significant (p=0.21). In our study patients with low platelet counts, none had MMSE score ≤23, while in high platelet count group 81.01% had MMSE score ≤23,(r=-0.440, 2=754.72, p=0.0001, S). No previous study was available for comparison between low platelet count and MMSE score (Table 12).

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• High-level peer review and editorial services in normal and high MPV group. Out of 1000 patients 223(22.3%) patients had depression score <5 and 777(77.7%) patients had depression score ≥5, MPV was positively correlated with depression score (r=0.889) and it was statistically significant (p=0.002) (2=693.82; p<0.0001 S-Significant). Similar results were seen in a study by Ataoglu et al. [19]. In this study out of 1000 patients 134(13.40%) patients were robust, 712(71.30%) patients were frail and 153(15.30%) patients were disable, there was a positive correlation between MPV and frailty score (r=0.705) and it was statistically significant (p=0.0001) (2=598.26;p<0.0001 S-Significant). There was no data of frailty with MPV. In our study out of 1000 patients 210(21%) patients had MMSE score ≤23 and 790(79%) patients had MMSE score >23. (r=0.388, 2=731.81; p=0.0001 S). Similar to our study Wang et al. [17] and Liang QC et al. [18] also compared MPV and PDW with MMSE score, and they showed significant correlation.

Conclusion
Elderly population are more prone to various psychological, physical and cognitive impairment hence our study provides evidence that platelet indices can be used as a potential biomarker to ascertain probable depression, frailty and cognitive function in elderly population. However more research are required on this topic to generalise in community.

Ethics Committee Approval
This study was approved by the ethical committee under the terms of the favourable approval by the Data Meghe institute of medical sciences (deemed to be university)[IEC reference number-DMIMS (DU)/IEC/2015-16/1489).