International Journal of Herbal Medicine 2020; 8(6): 28-32

E-ISSN: 2321-2187
P-ISSN: 2394-0514
www.florajournal.com Assessment of the differences between mean platelet
IJHM 2020; 8(6): 28-32
Received: 15-09-2020 volume (MPV) and platelet distribution width (PDW)
Accepted: 22-10-2020
values in flare and non-flare groups in Systemic Lupus
Indah Fitri Lestari Saragih
Department of Internal Erythematosus (SLE) patients
Medicine, Faculty of Medicine,
North Sumatera University
Medan, Indonesia Indah Fitri Lestari Saragih, Blondina Marpaung, Savita Handayani
Blondina Marpaung
Department of Internal Abstract
Medicine, Rheumatology Systemic Lupus Erythematosus (SLE) is an autoantibodies process against the cell nuclei and immune
Division of North Sumatera complex that will activate the inflammatory system causing the excitatory threshold of platelet activation
University Medan, Indonesia to be lower. Increase of significant mortality due to active disease (flare) SLE needs special attention.
Study of the association of Mean Platelet Volume (MPV) and Platelet distribution width (PDW) as a
Savita Handayani marker to predict SLE activity was still controversial. On the other hand, MPV and PDW can be
Department of Internal calculated easily in routine and low-cost laboratory tests. This study assesses the differences between
Medicine, Hematology and Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) values in flare and non-flare
Oncology Division of North groups in SLE patients. We found a significant difference in MPV values between flare compared to non-
Sumatera University flares groups. Based on Receiver Operating Characteristic (ROC) curve showed an optimal cutoff value
Medan, Indonesia
for MPV in the flare group is 9.15 fl and high sensitivity (90.6%). We recommend MPV value for initial
screening in the detection of active (flare) SLE.

Keywords: systemic lupus erythematosus, MEX-SLEDAI, mean platelet volume, platelet distribution
width

1. Introduction
Systemic Lupus Erythematosus (SLE) is an autoimmune disease signed with the absence of
autoantibodies against cell nuclei and immune complexes that will activate the inflammatory
system, thereby causing damage to the targeted organs[1-2]. The CDC Lupus registry estimates
an annual prevalence from 2002-2004 in Asia (94.7 and 56.2 per 100,000 people,
respectively). The yearly incidence of different racial/ethnic groups from 2002-2004 was
significantly higher for blacks than whites for Asians, the incidence being 4.2 and 3.8 per
100,000 people, respectively. SLE was identified as the cause of death, with an average of
2,061 deaths per year over the seven years [3]. Late diagnosis, poor therapeutic adherence, and
persistent SLE disease activity play a significant role in the prognosis of SLE patients [4]. The
MEX-SLEDAI Index evaluates SLE activity in the last ten days with 85.7% sensitivity and
100% specificity. The Mex-SLEDAI has scores from 0 to 24[5]. The pathogenesis of SLE
disease is not yet fully known. Antinuclear antibodies (ANA) and Anti-Ds-DNA antibodies are
the disease's hallmark and shall be the initial test performed in SLE. Autoantibodies may be
associated with a particular clinical subset of SLE, while others may serve as a marker of
disease activity [6]. Several studies found that platelets have an important role to play in
inflammatory processes and immune responses[7-9]. Hematologic manifestation can occur in
SLE were anemia, leukopenia secondary to neutropenia, lymphopenia, and thrombocytopenia
can be mild or severe [6]. These hematologic abnormalities are due to several immune and
nonimmune mediated mechanisms. It was associated with excessive production of cytokines,
antibodies, immune complexes, growth factor deficiencies, increased peripheral accumulation,
a decreased life span, reduced neutrophil functions, gastrointestinal losses, and toxicity of
medication [7]. SLE affects the numbers, ratios, and volumes of peripheral blood cells
involving Mean platelet volume (MPV) is a parameter of a complete blood cell count (CBC)
[7]
Corresponding Author: . Platelets (PLT) play a role in inflammatory reactions and immune response. Platelet
Indah Fitri Lestari Saragih distribution width (PDW) that shows the heterogeneity in PLT morphology is clinically related
Department of Internal to PLT activation. Several studies have reported that MPV and PDW are useful markers of
Medicine, Faculty of Medicine,
North Sumatera University
SLE disease activity was still controversial [7,10-14]. The low cost and widely available
Medan, Indonesia examinations, make this study focus on how MPV and PDW affect SLE disease activity [10].

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2. Materials and methods Research Ethical Committee. In this study, we assessed the
2.1 Materials course of SLE disease activity by scoring MEX-SLEDAI.
This study used a cross-sectional design inclusion 64 Patients who had their venous blood drawn for complete
respondents were selected consecutively in June 2020 among blood count (CBC). CBC was analyzed using an automated
SLE patients who came to H. Adam Malik Hospital. Inclusion hematology analyzer Sysmex XN-1000, then MPV and PDW
criteria were: men and women who were not pregnant aged > were noted. The normal value of PDW is 10.0 - 18.0% with a
18 years, patients diagnosed with SLE according to updates of decrease in value (PDW <10.0%) and an increase (PDW>
the American College of Rheumatology (ACR) revised 18.0%). MPV has a normal value of (6.5-9.5 fl) by indicating
criteria for the classification of SLE in 1997, each respondent a decrease in value (MPV <6.5 fl) and an increase (MPV> 9.5
were assessed the course of SLE disease activity by scoring fl). The research data were processed using SPSS 20th.
MEX-SLEDAI. The MEX-SLEDAI score ranges from 0 to
32; SLE flare (active) is defined as a MEX-SLEDAI score >5 2.2 Mathods
and SLE remission or inactivity score ≤2. All respondents Analysis data used univariate analysis to represent frequency
provided informed consents, and cooperative. The exclusion distribution of gender, age, MEX-SLEDAI score, platelet
criteria included SLE patients with a massive stress (severe count, ANA test, and anti-dsDNA.The bivariate analysis uses
trauma, surgery, cardiac shock, burns), severe renal to find out the difference in MPV and PDW values between
insufficiency (GFR) <30 ml/min), cirrhosis of the liver, flare and non-flare groups in SLE patients using the Mann-
having hematological disorders such as ITP, microtiter Whitney test. The data were considered as significant if the p-
hypochromic anemia, macrocytic anemia, or other diseases value was <0.05.
that directly affect platelet size and volume such as
hypertension, diabetes mellitus, obesity, dyslipidemia, and 3. Results & discussion
sepsis. This study had an ethical clearance approval from the 3.1 Results
Medical Faculty of North Sumatera University Health

Table 1: Characteristics of research subject

Variable Flare (n=32) Non-Flare (n=32) P-Value
Sex, n(%) 0.302
Male 3 (9.3) 1 (3.1)
Female 29 (90.7) 31 (96.9)
Age, Median (min-max) years 26 (18-45) 30 (19 -53) 0.463
Trombocytes 260156 ±92286 268968 ±85114 0.86
MEX-SLEDAI, Median (min-max) 12 (6-21) 2 (1-2) <0.001*
Anti dsDNA, Median (min-max) 190 (13.2-886.0) 55.6 (23.2-570.0) 0.005*
ANA Test, Median (min-max) 107.5 (11.0-257.0) 62.7 (14.0-268.0) 0.113
Anti dsDNA: Antibodi Anti-double stranded DNA; ANA: Antinuclear Antibodies test; *p<0.05

The characteristic of research subject (table 1) in the flare

group showed the most commonly were female 29 (90.7%)
with an age range of 18–45 years, average platelet count
(260156), median MEX-SLEDAI score=12, Anti-ds DNA
level 190 (13.2-88.0) and ANA test level 107.5 (11.0-257.0).
In the non-flare group, the majority were female 31 (96.9%)
with an age range of about the same as flares group of 19 – 53
years, average platelet count (268.968), median MEX-
SLEDAI score=2, the Anti-ds DNA level 55.6 (23.2-570.0)
and ANA tests 62.7 (14.0-268.0).
Based on the frequency distribution of respondent
characteristics between the SLE flare group and the non-flare
group, the Mann-Whitney test showed significant difference
in the MEX-SLEDAI score (p<0.001) and Anti ds DNA
(p=0.005).

Table 2: The Relationship of MPV, PDW levels to flare and non-

flare SLE groups
Variable Flare (n=32) Non-Flare (n=32) P-Value Fig. 1 ROC curve of MPV levels in the flare group.
MPV, Mean ± SD 9.03±2,02 10.350 ± 1.09 0,002*
PDW, Mean ± SD 11.75±3,14 10.560 ± 2.13 0,083 3.2 Discussion
MPV: Mean Platelet Volume; PDW: Platelet Distribution Width, Most of the respondents with SLE were female. In general,
*p<0.05 SLE affects females most commonly than males with a ratio
(12: 1) [15]. This fact associated with hormonal impact is a
MPV and PDW as a biomarker for the course of SLE in table significant risk factor for SLE. Estrogens and prolactin induce
2 shows a significant difference in the mean MPV value in the autoimmunity and increase the B-cell activation factor
flare group higher than the non-flare group [(9.020 + 2.010 production and modulate lymphocyte and pDC activation. In
vs. 10.35 ± 1.09) fl, (p = 0.002)]. Eventhough the mean value contrast, androgens are considered protective in SLE [6].
of PDW was not statistically significant. Several studies also found that the majority of SLE patients
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were female such as study in Colombia (84.5%), Sweden patients than RA [(9.5 ± 1.7 vs. 8.7 ± 1.6) fl, p<0.05)][7]. On
(87%), and Jakarta (98.4%) [16-18]. The age range of the other hand, another study stated that the results were
respondents with SLE in the flare group was 26 (18-45) years different obtaining a higher MPV value in the flare than non-
in line with other studies that found almost the same that the flare in juvenile SLE patients statistically significant
median age of SLE group was 47 years, (18-64) years, and 19 (p=0.001) and also positively correlated with SLEDAI scores
- 50 years[11,19-20]. (p=0.01, r=0.55)[14]. Study Islamoglu et al. found no
The laboratory results showed that the mean platelet count significant difference in MPV value between patients with
was lower in the flare group than in the non-flare SLE group Discoid Lupus Erythematosus (DLE) and the control group
(260156 ± 92286 vs. 268968 ± 85114). In line with the (p=0.160), where the limitation of the study was a
previous study showed that the platelet count was lower in the retrospective design that collected minimal data on a
flare group SLE (268.88 ± 870.02 vs. 271.72 ± 698.07)[11]. patient[19].
However, another study found that the SLE in the non-flare Based on this study, the PDW value was higher in the flare
group had a lower value than the flare group (244.0 ± 49.5 vs. group compared with the non-flare group but not statistically
270.0 ± 105700)[12]. significant [(11.75 ± 3.14 vs. 10.56 ± 2.13), (p = 0.083)]. In
There was a significant difference in the value of Anti dsDNA line with study Sherif et al., showed that the difference of
between the SLE flare group and the non-flare group [190 PDW values in 80 (mild - severe) flares compared to non-
(13.2-886) vs. 55.6 (23.2-570), (p = 0.005)]. Gheita et al. flare SLE patients with controls group were mild flare (13.35
showed the same result, where the mean value of anti dsDNA ± 2.27), moderate flare (13.81 ± 2.98), severe flare (12.68 ±
increased significantly compared to the control group based 3.06) non flare group (12.94 ± 3.0) and control group (14.27 ±
on SLE disease activity criteria with SLEDAI and 2.17) statistically not significant (p=0.367)[20]. The study of
SLICC/ACR scores [(133.2 ± 100.50 vs. 22.03 ± 17.20) Islamoglu et al. also showed no significant difference in PDW
IU/mL, (p<0.0001)][21]. Study Narayanan K. also showed a value between DLE patients and the control group [(16.4 ±
significant positive correlation between the Anti-dsDNA 2.7 vs. 16.4 ± 0.78) (p=0.988)][19].
value and the SLEDAI score (p=0.01)[22]. In contrast, Chen et al. found that the PDW value in SLE was
The antinuclear antibody (ANA) is a general term for significantly increased in the flare compared to the non-flare
autoantibodies against various nuclear components that can be SLE group [(14.31 ± 2.90 vs. 12.15 ± 1.55), (p<0.001)], but
seen in all kinds of rheumatic diseases. Anti-double-stranded the limitation of the study was the relatively small number of
DNA (ds-DNA) dsDNA antibodies are useful in confirming samples, which affects external validation[10]. In comparison,
the diagnosis in the clinical settings when SLE is likely to be the study of He et al. (2020) obtained higher PDW values in
the diagnosis, because high concentrations of anti-ds-DNA SLE patients with Pulmonary Arterial Hypertension (PAH)
antibodies are almost exclusively present in SLE patients, than SLE without PAH. PDW and MPV values have a
anti-ds-DNA antibodies are SLE-specific. Qu et al. showed a negative correlation between platelet counts and PDW (r = -
sensitivity of ANA (95.36%) and specificity of the anti-ds- 0.770; p <0.05), MPV (r=-0.523; p <0.05), in other words, the
DNA antibody (96.90%) in SLE diagnosis. ANA has the lower of platelet count correlate in increasing PDW and MPV
highest sensitivity in the diagnosis of SLE, but its specificity values in dengue shock syndrome and DHF respondents[26].
is the worst. Otherwise, anti-ds-DNA antibody has the lowest Characteristic signs of chronic inflammatory disease were
sensitivity for SLE diagnosis, but the highest specificity. abnormal immune system regulation, and persistent
Eventhough, they have limited usefulness in monitoring inflammation affects the hematopoiesis system. Peripheral
disease activities and in predicting flares [23,24]. blood cell changes use to diagnose disease activity and
Complete blood count parameters provide a significant several collagen diseases such as RA, SLE, and Sclerosis [7].
marker of systemic inflammation. PDW and MPV became Platelets can form ROS (reactive oxygen species). Oxidative
popular and vital markers of platelet activation. Studies with stress plays a role in the inflammatory process, will activate
SLE showed lower MPV scores and higher PDW scores in platelets so that platelets have a primary role in the
patients and a positive relationship between PDW and disease pathophysiology of disease [27]. Other platelet function
activity [10,25]. In contrast, a study in DLE patients found no markers such as PDW, can represent the heterogeneity of
significant difference between PDW and MPV levels in the platelet morphology and are clinically associated with platelet
healthy control group [19]. activation. Also, MPV assesses the platelet size most
MPV has been considered a reliable marker to indicate frequently used. These parameters evaluate in routine blood
platelet activation and inflammation. Decreased MPV levels tests [10].
were observed in patients with SLE associated with an active The heterogeneity of MPV and PDW values may be due to
inflammatory state associated with disease activity [25]. differences in patient clinical characteristics, treatment
Decreasing MPV value is caused by large consumption and strategies, race, and sex comparisons. The mechanism of
activated platelets in the place of extravascular inflammation decreasing MPV value in flare group SLE patients was
[13]
. This study found MPV in SLE respondents was associated with the release of proinflammatory platelet
significantly lower in the flare than in the non-flare group bioactive molecules. Excess production of proinflammatory
[(9.02 + 2.01 vs. 10.35 ± 1.09) fl (p=0.002). In line with cytokines can suppress the bone marrow, followed by the
others studies such as Safak et al., [(7.66 ± 0.89 vs. 8.62 ± 1, creation of smaller platelet sizes. The increase in MPV in SLE
06) fL, (p<0.0001)][25], Hartmann et al., [(10.0 ± 0.7 vs. (10.7 patients in the flare group tends to be associated with vascular
± 1.0) fl, (p = 0.005)][12], Garcia et al [(7.16 ± 1.39 vs. 8.16 ± events, thrombocytopenia, and condition after receiving
1.50) fl (p=0.005)][11] and Chen et al [(10.74 ± 0.94 vs. 11.09 treatment [20].
± 1.14), p<0.001][10]. Mean platelet volume in the flare group SLE respondents had
The amount of inflammation affected the decreasing MPV a cutoff of 9.15 fl with sensitivity (90.6%) and specificity
values in RA and SLE patients due to the high consumption (66%). Previous studies had cutoff value results for MPV in
of large platelets in the area of inflammation (p<0.004)[13]. the flare SLE group, such as the Hartman et al. 9.85 fl with
The MPV value showed a significantly higher amount in SLE sensitivity (61%) specificity (24%) [12], Garcia et al. 8.32 fl
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with sensitivity (86%) and specificity (41%)[11], Yavuz et al. Cruz IM, Salgado DB et al. `Mean platelet volume is
8.4 fl with sensitivity (75%) and specificity (90%)[14]. The decreased in adults with active lupus disease, Elsevier,
limitations of this study were the delayed time between 2016;5:274
sampling and examination of the sample, small amount 12. Hartmann LT, Alegretti AP, Machado AB, Martins AF,
number of samples, and do not involve observation of the Chakr RM, Gasparin AA et al. Assesment of Mean
history of drug use and treatment activities in disease so that it Platelet Volume in Patients with Systemic Lupus
can bias the results of the study. Erythematosus. The Open Rheumatology Journal
2018;12:129-138
4. Conclusions 13. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD.
This study concludes that the mean MPV value has a Mean platelet volume: a link between thrombosis and
significant difference between a flare and non-flare group of inflammation?, Curr Pharm Des 2011;17(1):47-58.
SLE. The AUC curve shows an optimum cutoff value of the DOI: 10.2174/138161211795049804
flare group (9.15 fL) and high sensitivity. We recommend 14. YavuzS., Ece, A. Mean platelet volume as an indicator of
MPV for initial screening in the detection of active (flare) disease activity in juvenile SLE. Clin Rheumatol 2014;
SLE. 33:637–641.
https://doi.org/10.1007/s10067-014-2540-3.
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