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dOI 10.11603/IJMMR.2413-6077.2020.2.11509

EFFECTS OF HEMOTOXIC SNAKE BITE ENVENOMATION  
ON HAEMATOLOGICAL PARAMETERS VARIABILITy IN PREDICTING 
COMPLICATIONS

M.P. Harikrishnan, *C.R. Anil Kumar, M.K. Anand, J. Earali
JUBILEE MISSION MEDICAL COLLEGE AND RESEARCH INSTITUTE, THRISSUR, INDIA

Background. Snake bite envenomation is a major public health problem in India with a high mortality rate. 
The major complications following a hemotoxic snake bite are disseminated intravascular coagulation (DIC), 
shock, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS) and coagulopathy. The study explores 
a possible correlation of the haematological parameters studied to complications like DIC, AKI, acute renal failure 
(ARF), ARDS, shock and gastrointestinal (GI) bleed. 

Objective. The aim of the study was to find out the effect of snakebite envenomation on the major 
haematological parameters of the body in relation to complications.

Methods. This cross-sectional study was conducted during a period of 18 months. 150 patients were included 
in the study after obtaining their informed consents. Data collection was done using a proforma. The study also 
compared clotting time (CT) by capillary tube method and whole blood clotting time at 20 minutes (WBCT20). 
SPSS software was used for statistical analysis.

Results. Among the people with complications, the majority (52%) of participants had AKI, 26% of them 
requiring dialysis, 16.7% participants had GI bleed, 11.3% participants had shock and 10% participants had DIC.

Conclusions. A prolonged bleeding time was found to be one of the most helpful haematological parameters 
in predicting shock and AKI. Clotting time by both capillary tube and WBCT20 methods were comparable in 
predicting complications.

KEyWoRdS: hemotoxic snake bite; acute kidney injury; shock; clotting time; bleeding time.

*Corresponding author: Anil Kumar CR, Associate Professor, 
Jubilee Mission Medical College and Research Institute, Thris-
sur, 680005, India. E-mail: anilkumarcr3005@gmail.com

International Journal of Medicine and Medical Research 
2020, Volume 6, Issue 2, p. 22-29
copyright © 2020, TNMU, All Rights Reserved

M.P. Harikrishnan et al.

Introduction 
Snakebite envenomation is a major public 

health problem in India with a high mortality 
rate [1]. The WHO estimates that there are 
81000 snake envenomation in India per annum 
with a mortality of 11000 (13.5%) [2]. It has been 
reported that there are 5 million snake bites 
with 2.5 million envenomation and 125,000 
fatalities worldwide annually [3]. India is 
reported to have the highest number of snake 
bites (81,000) and deaths (11,000) per year [3]. 
Snakebite is considered as one of the neglected 
tropical diseases by the WHO [4]. The mortality 
due to snakebites in India is due to various 
socioeconomic, cultural and environmental 
causes [5]. Among the 52 species of venomous 
snakes in India, 4 species are responsible for 
greatest number of snake bites which are 
medically significant. These are referred to as 
the big four, Bungarus caeruleus (common 
krait), Daboia russelii (Russel’s viper), Echis 
carinatus (saw scaled viper), Naja naja (Indian 
cobra). But recently it has been discovered that 
another species, the hump-pit viper (Hypnale 

hypnale), is capable of causing lethal enve-
nomation [6].

The venomous snakes found in India can 
be classified per the type and action of venom 
as Neurotoxic (Cobra, Krait) and Hemotoxic 
(Vipers). Then main complaints are pain and 
swelling at the site of snake bite [7–11].

The major complications following hemo-
toxic snake bite are disseminated intravascular 
coagulation (DIC), shock, acute kidney injury 
(AKI), acute respiratory distress syndrome 
(ARDS) and coagulopathy [12]. AKI is one of the 
serious complications developing after snake 
bite [13,14]. Early identification of hemotoxic 
envenomation and anti-snake venom (ASV) 
administration may help decrease morbidity 
and mortality [15].

The study tries to find out the common 
complications after hemotoxic snake bites and 
to explore a possible correlation of the haema-
tological parameters to complications. The 
study also compares clotting time by capillary 
tube method and WBCT20. ASV administration 
is currently based on prolongation of WBCT20. 
Capillary tube method for estimating CT could 
be used in a resource poor setting, if the 



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predictability of the test is comparable to that 
of WBCT20. In a study by Ratnayake et al [16] 
the diagnostic utility of WBCT20 was determined 
at the time of admission and it was found out 
that it had got sensitivity of 82% and specificity 
of 98% in detecting venom induced consumption 
coagulopathy (VICC). The aim of the study was 
to assess the value of haematological para-
meters, i.e. bleeding time (BT), clotting time 
(CT), prothrombin time (PT), activated partial 
thromboplastin time (aPTT) in predicting the 
complications. The primary objective was to 
assess the effect of snake bite on the major 
haematological parameters of the body in 
relation to complications. 

Methods
This cross-sectional study was conducted 

over a period of 18 months after obtaining 
clearance from the institutional ethics com-
mittee. A total of 150 patients, who were above 
18 years of age, had given written informed 
consent and had clinical features of hemotoxic 
envenomation or increase of any of the eva-
luated haematological parameters as bleeding 
time (BT), clotting time (CT), prothrombin time 
(PT), activated partial thromboplastin time 
(aPTT), were included in the study. Convenient 
sampling was done. 

The patients who had not given written 
informed consent and the patients with bites 
other than hemotoxic snakebites were excluded 
from the study. Any patient who is a known case 
of bleeding disorder, chronic alcoholic, with 
acute or chronic liver disease, pregnant females 
and on anticoagulation therapy were excluded 
from the current study. After admission a comp-
lete history was taken and a thorough clinical 
examination was conducted. As per the pro-
tocol followed in our Institute, all patients bitten 
by poisonous snakes received polyvalent anti 
snake venom (ASV), within 15 minutes of 
reaching the hospital, provided they had clinical 
features of envenomation. The patients with 
no initial features of envenomation were ad-
ministered with ASV as soon as they exhibited 
first signs of envenomation.

Initial blood samples collected from the 
patients admitted with hemotoxic envenomation 
were sent for complete hemogram, random 
blood sugar (RBS), renal function tests (RFT), 
liver function tests (LFT), serum electrolytes and 
important coagulation parameters including 
BT, CT (both WBCT20 and capillary tube me-
thods), PT with INR, D-dimer and a PTT. All 
patients with features of envenomation were 

administered with 10 vials of ASV. The response 
was monitored clinically by doing WBCT20 and 
Clotting Time (CT) using the capillary tube 
method, with 2 hour intervals if prolonged 
initially, otherwise with 6 hour intervals.

If the features of envenomation were per-
sistent or if the WBCT20 was prolonged after 6 
hours of first dose, a repeated dose of 10 vials 
of ASV was given. Blood parameters like BT, CT, 
PT, APTT and D-dimer were investigated as per 
the protocol. The first sample of blood was 
taken on admission for evaluating BT, CT, PT 
with INR, and APTT. BT was subsequently 
estimated 2 times with a 5 minute interval, then 
in 2 hours, 4 hours, and 6 hours after admission. 
Then every 6 hours if prolonged. Once normal, 
it was repeated once daily. CT was estimated 
at time of admission. If in norm, CT was re-
peated with 6 hour intervals for 1 day to test 
for requirement of ASV. If prolonged, it was 
tested with 2 hour intervals till the normal rate. 
CT was estimated by 20-minute whole blood 
clotting method (WBCT20) and capillary tube 
method for comparison study. APTT was done 
on the 1st day and 7th day, but PT was done at 
the time of admission and daily. D-dimer was 
done when there was prolongation of CT on 3 
consecutive occasions. ASV was given according 
to the standard protocol with administration of 
ASV every 6 hours till normal coagulation 
profile. 

A bite was considered hemotoxic, if the 
culprit snake is identified as hemotoxic or by 
coagulopathy as suggested by haematological 
parameters. aKi was defined as the increase of 
serum creatinine ≥0.3 mg/dL within 48 hours 
or increase in serum creatininein ≥1.5 times 
from baseline. AKI staging was performed 
according to the “Kidney disease: improving 
global outcomes” (KDIGO) clinical practice 
guidelines [17]. Shock was defined by a systolic 
blood pressure of <90 mmHg with evidence of 
tissue hypoperfusion (<0.5 mL/kg/h decrease 
in urine output, cold skin, and or requiring 
inotropic drugs). The data was collected, 
occurrence of complications and derangement 
in haematological parameters were studied and 
analysed. The data collected was recorded in a 
standard data collection sheet as per study 
proforma and later transferred to Microsoft 
Excel spread sheet for statistical analysis. 
Complications like AKI, shock were considered 
as primary outcome variables. CT by capillary 
tube and WBCT20 at different time periods, BT, 
PT, aPTT etc. were considered as explanatory 
variables. 

M.P. Harikrishnan et al.



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Descriptive analysis was carried out by 
frequency and proportion for categorical 
variables. Categorical outcomes were compared 
between the study groups using the Chi square 
test / the Fisher's Exact test (if the overall 
sample size was <20 or if the expected number 
in any one of the cells was <5, Fisher's exact 
test was used). P value <0.05 was considered 
statistically significant. iBm SPSS version 22 was 
used for statistical analysis [18]. 

Results
In the study it was observed that the snake 

bites were more common in males. Out of 150 
subjects in our study, 24 (16.0%) cases, were 
bites by Russel’s viper, 4 (2.7%) cases by krait, 
2 (1.3%) cases by hump nosed pit viper and 120 
(80.0%) were unidentified. The patients included 
in the study, who had any comorbidity, 
accounted for 36.0% of the study population 
(Table 1). 

Among the complications, the majority 
(52%) of participants had AKI, 26% of them 
required dialysis; 16.7% participants had GI 
bleed; 11.3% participants had shock and 10% 
participants had DIC (Table 2).

Association between AKI and shock with 
various parameters have been shown in the 
Table below (Table 3). At the time of admission, 
11 patients (47.8%) presenting with AKI 
reported prolonged CT (capillary tube). 
However, in 6 hours 22 (100%) participants with 
prolonged CT had AKI. A majority of 36 (60%) 
participants reported AKI with normal WBCT20 
at the time of admission. The occurrence of AKI 
was evidenced in 30 (81%) participants with 
prolonged WBCT20 in 6 hours. The occurrence 
of AKI was found in 17 (58.6%) participants with 
PT >16.50 seconds. all participants with aPTT 
>35 reported aKi (Table 3). WBCT20 and CT by 
ca pilla ry t ube met hod in 6 hours were 
comparable in predicting AKI.

Table 1. Summary of baseline parameters in study population (n= 150)

Parameter Summary (number, %)
Age

18-30 37 (24.7%)
31-40 30 (20%)
41-50 29 (19.3%)
51-60 27 (18%)
61-65 27 (18%)

Gender
Male 98 (65.3%)
Female 52 (34.7%)

Place of Bite
Indoor 1 (0.7%)
Outdoor 149 (99.3%)

Snake Type
Russel’s Viper 24 (16%)
Krait 4 (2.7%)
Hump nosed pit viper 2 (1.3%)
Unidentified 120 (80%)
Classical Bite 43(28.7%)
Local Reaction 65 (43.3%)
Cellulitis  27 (18%)
Gangrene 8 (5.3%)
Ecchymoses/Bleeding 14 (9.3%)
Comorbidities  54 (36%)
Pain at bite site 128 (83.3%)
Numbness 125 (83.3%)
Sweating 98 (65.3%)
Periorbital oedema 71 (47.3%)
Vomiting 64 (42.7%)
facial puffiness 48 (32%)

Parameter Summary (number, %)
Abdominal pain 45 (30%)
Neurological signs 28 (18.7%)
Respiratory distress 25 (16.7%)
Low back ache 20 (13.3%)
Bleeding from any site 15 (10%)
Respiratory failure 15 (10%)
ARDS 11 (7.3%)
Hematemesis 4 (2.7%)

Comorbidities
Diabetes Mellitus 25 (16.7%)
Hypertension 24 (16%)
Ischemic Heart  
Disease

0 (0%)

Respiratory Failure 0 (0%)
Bronchial Asthma 11 (7.3%)
Chronic Obstructive 
Lung Disease

23 (15.3%)

CT prolonged
At the Time of admission 23 (15.3%)
2 Hours 36 (24%)
4 Hours 29 (19.3%)
6 Hours–12 hours 49 (32.03%)
Day 2 4 (2.7%)

WBC T20-Prolonged
At the time of admission 90 (60%)
2 Hours 61 (40.7%)
4 Hours 48 (32%)
6 Hours–12 hours 86 (57.3%)
Day 2 15 (10%)

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The occurrence of shock was found in 6 
(26.1%) participants with prolonged CT at the 
time of admission (P value of 0.039). However, 
11 (50%) participants had shock with prolonged 
CT in 6 hours (P value <0.001). The occurrence 
of shock was found in 11 (12.2%) participants 
with normal WBCT20 at admission. 17 (42%) 
participants with prolonged WBC T20 in 6 hours 

reported shock. The occurrence of shock was 
found to be statistically significant with p value 
of <0.001 and the proportion of shock was 8 
(66.7%) with BT >7 seconds. The occurrence of 
shock was found to be significant with a P value 
of <0.001 in 7 (30.4%) participants with >35 aPTT 
(Table 4).

Table 2. Summary of the complications observed (N=150)

Complications Summary (number, %)
AKI 78 (52%)
Acute Renal Failure (AKI requiring dialysis) 39 (26%)
Dialysis done 39 (26%)
GI Bleed 25 (16.7%)
Shock 17 (11.3%)
DIC 15 (10%)
ARDS 11 (7.3%)
Reaction to ASV 6 (4%)
Mortality 2 (1.3%)
Intra Cerebral Bleed 0 (0%)
Hypopituitarism 0 (0%)
Guillain Barre Syndrome 0 (0%)
Peripheral Neuropathy 0 (0%)

Table 3. Association of different parameters with AKI

Parameter
AKI

P Value
Present Absent

CT capillary tube at the time of admission
Prolonged (N=23) 11(47.8%) 12 (52.2%)

0.663
Normal (N=127) 67 (52.8%) 60 (47.2%)

CT capillary tube in 6 hours
Prolonged (N=22) 22 (100%) 0 (0%)

*
Normal (N=120) 48 (40%) 72 (60%)

WBCT20 at admission
Prolonged (N=90) 42 (46.7%) 48 (53.3%)

0.109
Normal (N=60) 36 (60%) 24 (40%)

WBCT20 at 6 hours
Prolonged (N=37) 30 (81%) 7 (19%)

<0.001
Normal (N=105) 40 (38%) 65 (62%)

BT
>7 (n=12) 12 (100%) 0 (0%)

*
≤7 (n=138) 66 (47.8%) 72 (52.2%)

PT
>16.50 (n=29) 17 (58.6%) 12 (41.4%)

0.319
≤16.50 (n=116) 56 (48.3%) 60 (51.7%)

APTT
>35 (n=23) 23 (100%) 0 (0%)

*
≤35 (n=123) 51 (41.5%) 72 (58.5%)

*No statistical tests were applied due to 0 values in one of the cells.

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Discussion
In this study, shock was seen in 11.3% of the 

total cases, AKI in 52 %, ARF (AKI requiring 
dialysis) in 26% and gastro intestinal bleed in 
16.7%. A comparatively higher incidence of 
shock was reported by Harshavardhan et al. 
[19] in their study on hemotoxic snake bite 
cases (36%). But a comparable value (10.38%) 
to our study was reported by Kumar et al. [20].

Acute kidney injury (AKI) was established in 
52% of the cases in the present study. A so-
mewhat similar value was observed (30.71%) 
in a previous study [21]. Bhalla et al studied the 
clinical profile of snake bite in a tertiary centre 
and observed AKI in 47.6% of the cases [22]. 
Similar study on outcomes of snakebite 
poisoning in a tertiary centre by Meenakshi B 
et al. reported AKI in 44% of cases.

Proteins are an important constituent of 
snake venoms and they are encoded by poly-
adenylated mRNA in the venomous glands (12S 
and 20S) [21]. Besides proteins, the other 
components present in snake venom include 
lipids, polysaccharides, nucleotides, nucleosides, 
free amino acids, riboflavin, serotonin and 
histamine. Pharmacologically active substances 

of the venom are enzymes and low molecular 
weight peptides. The main sites of action of 
these enzymes are cell membranes, the vas-
cular wall and the blood coagulation cascade 
[20, 22]. Snake venom, mainly those of Viperidae, 
contain also molecules that act on the four 
interconnected blood systems (i) the coagulation 
system, (ii) fibrinolytic system, (iii) complement 
and (iv) the kinin system [22]. 

Shock is consistently the single most 
important factor in mortality due to Indian viper 
bite poisoning. The pattern of shock observed 
shows early transient shock, early sustained 
shock and late onset shock. Shock is caused by 
reduction in the circulating blood volume due 
to a venom-mediated generalized increase in 
endothelial permeability. Apart from this, 
massive limb oedema can lead to considerable 
compartmentalization of blood and plasma. 
Pulmonary intravascular coagulation, pul-
monary oedema caused by increased pulmonary 
vascular permeability, and cardiotoxic effects 
of the venom may also be contributory.

The kidney is a highly vascularized organ 
with excretory function, so it is prone to venom 
toxicity. aKi, the most significant of all the renal 

Table 4. Association of different parameters with shock

Parameter
Shock

P Value
Present Absent

CT capillary tube at the time of admission
Prolonged (N=23) 6 (26.1%) 17 (73.9%)

0.039
Normal (N=127) 11 (8.7%) 116 (91.3%)

CT capillary tube at 6 Hours
Prolonged (N=22) 11 (50%) 11 (50%)

<0.001
Normal (N=120) 6 (5%) 114 (95%)

WBCT20 at Admission
Prolonged (N=90) 11 (12.2%) 79 (87.8%)

0.875
Normal (N=60) 6 (10%) 54 (90%)

WBCT20 at 6 Hours
Prolonged (N=37) 17 (46%) 20 (54%)

*
Normal (N=105) 0 (0%) 105 (100%)

BT
>7 (n=12) 8 (66.7%) 4 (33.3%)

<0.001
≤7 (n=138) 9 (6.5%) 129 (93.5%)

PT
>16.50 (n=29) 12 (41.4%) 17 (58.6%)

*
≤16.50 (n=116) 0 (0%) 116 (100%)

APTT
>35 (n=23) 7 (30.4%) 16 (69.6%)

<0.001
≤35 (n=123) 6 (4.9%) 117 (95.1%)

*No statistical tests were applied due to 0 values in one of the cells.

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manifestations, has been reported to be of 
varying frequency in different studies [23]. 
Many studies have appeared in literature on 
snake bite-induced AKI over a decade. Phos-
pholipase A2 is the most widespread and 
extensively studied of all venom enzymes. It 
damages mitochondria, red blood cells, leu-
cocytes, platelets, skeletal muscle, vascular 
endothelium, and other membranes and leads 
to auto pharmacological release of histamine 
and anti-coagulants. Viper bites cause various 
systemic symptoms such as coagulopathy, 
haemolysis, AKI, a generalized increase in 
capillary permeability and rhabdomyolysis [23]. 
Haemoglobinuria caused by intra-vascular 
haemolysis and myoglobinuria resulting from 
rhabdomyolysis contributes to development of 
AKI. Haemorrhage, hypotension, disseminated 
intravascular coagulation, intravascular hae-
molysis, and rhabdomyolysis enhance renal 
ischemia leading to renal failure. Enzymatic 
activities of snake venoms account for direct 
nephrotoxicity and immunologic mechanism is 
insignificant [24].

A variety of factors contribute to shock like 
fright, hypovolemia (due to extravasation of 
fluids and blood loss), myocardial depression, 
haemorrhage into the adrenals and pituitary. 

Conclusions
A prolonged clotting time as obtained by 

capillary tube method in 6 hours is helpful in 
predicting development of shock. However, 
since AKI occurred even in those patients 
having normal clotting time and WBCT20, these 
parameters may not be useful as predictors of 
AKI. Prolonged CT by capillary tube method and 
WBCT20 in 6 hours were comparable in pre-
dicting AKI. Prolongation of more than 16.5 
seconds in prothrombin time was helpful in 

predicting the development of shock. However 
prolonged prothrombin time (>16.50) was not 
useful in predicting AKI. A prolonged APTT more 
than 35 seconds was helpful in predicting the 
onset of shock and AKI. A prolonged bleeding 
time was found to be one of the most helpful 
haematological parameters in predicting shock 
and AKI.

Limitations of the study
A comparatively low number of 150 cases 

may have strained the generalizations derived 
by the study. Parameters like CT by capillary 
tube method did not have a control test 
measured in patients with non-poisonous 
snake bite envenomation. A degree of individual 
variability was inevitable in the evaluation of CT 
both by capillary tube and WBCT20 methods as 
well as that of BT. The duration of envenomation 
prior to admission has not been taken into 
account in this study, possibly affecting the 
correlation between haematological parameters 
and development of complications.

Conflicts of Interest
authors declare no conflict of interest.
Authors’ Contributions
Harikrishnan M.P. – data curation; inves-

tigation; methodology; supervision; writing –
original draft; writing – review & editing. 

Anil Kumar C.R . – data curation; investigation; 
supervision; project administration; metho-
dology; supervision; writing – original draft; 
writing – review & editing. 

Anand M.K. – data curation; investigation; 
methodology; supervision; writing – original 
draft; writing – review & editing. 

Jerry Earali – data curation; investigation; 
methodology; supervision; writing – original 
draft; writing – review & editing. 

ВАРІАБЕЛЬНІСТЬ ГЕМАТОЛОГІЧНИХ ПАРАМЕТРІВ ЯК ПРЕДИКТОР 
РОЗВИТКУ УСКЛАДНЕНЬ ПІСЛЯ ПОТРАПЛЯННЯ В ОРГАНІЗМ 
ГЕМОТОКСИЧНОЇ ОТРУТИ ВНАСЛІДОК УКУСУ ЗМІЇ 

M.P. Harikrishnan, *C.R. Anil Kumar, M.K. Anand, Jerry Earali
JUBILEE MISSION MEDICAL COLLEGE AND RESEARCH INSTITUTE, THRISSUR, INDIA

Вступ. одна з найбільших проблем закладів охорони здоров’я в індії – укуси змій, які супроводжуються 
високою летальністю. найбільш часті ускладнення, які розвиваються внаслідок потрапляння в організм 
гемотоксичної зміїної отрути, це синдром дисемінованого внутрішньосудинного згортання (двЗ), шок, 
гостре ураження нирок (Гун), гострий респіраторний дистрес синдром (Грдс) та кооагулопатія. 

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мета дослідження – дослідити можливий взаємозв’язок між частотою розвитку ускладнень як 
двЗ, Гун, гостра ниркова недостатність (Гнн), Грдс, шок та кишково-шлункові кровотечі. 

Методи. це перехресне дослідження проводилося впродовж 18 місяців. було залучено 150 пацієнтів, 
які підписали поінформовану згоду. Збір даних проводили за допомогою спеціально розробленої форми. 
Також досліджували швидкість згортання крові за допомогою капіляра та 20-хвилинного тесту на 
згортання цільної крові (англ. 20WBCT, показники коагулограми. для статистичної обробки отриманих 
даних використовували програмне забезпечення IBM SPSS Statistics. 

Результати. серед покусаних людей, у яких розвинулися ускладнення, у більшості (52%) розвинулося 
Гун, внаслідок чого 26% серед них потребували діалізу, у 16,7% учасників дослідження були кишково-
шлункові кровотечі, у 11,3% - розвинувся шок, у 10% розвинувся двЗ.

Висновки. серед досліджуваних гематологічних параметрів для прогнозування розвитку 
ускладнень (гострого ураження нирок та шоку) після укусу змії найбільш інформативними був 
подовжений час згортання крові. обидва методи дослідження згортання крові і за допомогою капіляра 
і WBCT20 були релевантні та корелювали при прогнозуванні ускладнень.

КЛЮЧОВІ СЛОВА: гемотоксична зміїна отрута; укус змії; гостре ураження нирок; шок; час 
згортання крові; час кровотечі. 

Information about the authors
Harikrishnan M.P. – Senior Resident, MD General Medicine, Department of Medicine, Jubilee Mission 

Medical College and Research Institute, Thrissur.
oRCid: 0000-0003=3452-5588 email: harikrishnapuram@gmail.com
Anil Kumar C.R. – MD General Medicine, Associate Professor, Department of Medicine, Jubilee Mission 

Medical College and Research Institute, Thrissur.
oRCid: 0000-0002-6397-2005 email: anilkumarcr3005@gmail.com
Anand M.K. – MD General Medicine, Assistant Professor, Department of Medicine, Jubilee Mission 

Medical College and Research Institute, Thrissur.
oRCid: 0000-0002-0164-8402 email: anandmk92@yahoo.in
Jerry Earali – MD General Medicine, Professor, Department of Medicine, Jubilee Mission Medical College 

and Research Institute, Thrissur.
oRCid: 0000-0003-2880-1259 email: jeyearali@gmail.com

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Received 16 Nov 2020; revised 3 Dec 2020;  
accepted 7 Dec 2020.

This is open access article distributed under the Creative Com-
mons Attribution License, which permits unrestricted use, 
distribution, and reproduction in any medium, provided the 
original work is properly cited.

M.P. Harikrishnan et al.