Accepted Manuscript Mean Platelet Volume, a novel biomarker in adolescents with severe Primary Dysmenorrhea Suna Kabil Kucur, Ali Seven, Kadriye Beril Yuksel, Halime Sencan, Resident, Ilay Gozukara, Nadi Keskin PII:
S1083-3188(16)00164-9
DOI:
10.1016/j.jpag.2016.01.128
Reference:
PEDADO 1961
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 10 January 2016 Accepted Date: 31 January 2016
Please cite this article as: Kabil Kucur S, Seven A, Yuksel KB, Sencan H, Gozukara I, Keskin N, Mean Platelet Volume, a novel biomarker in adolescents with severe Primary Dysmenorrhea, Journal of Pediatric and Adolescent Gynecology (2016), doi: 10.1016/j.jpag.2016.01.128. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Mean Platelet Volume, a novel biomarker in adolescents with severe Primary Dysmenorrhea KABIL KUCUR Suna, Assist Prof, Dumlupinar University Medical Faculty Evliya Celebi Training and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani
RI PT
Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected], Gsm: +905323559047
SEVEN Ali, Assist Prof, Dumlupinar University Medical Faculty Evliya Celebi Training and
SC
Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected]
M AN U
YUKSEL Kadriye Beril, Assist Prof, Dumlupinar University Medical Faculty Evliya Celebi Training and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected] SENCAN Halime, Resident, Dumlupinar University Medical Faculty Evliya Celebi Training
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and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected] GOZUKARA Ilay, Assist Prof, Mustafa Kemal University Medical Faculty, Department of
EP
Obstetrics and Gynecology, [email protected] KESKIN Nadi, Assoc. Prof, Dumlupinar University Medical Faculty Evliya Celebi Training
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and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, nadi [email protected] Running title: Mean Platelet Volume in adolescents with Primary Dysmenorrhea
ACCEPTED MANUSCRIPT Abstract Study objective: To evaluate whether mean platelet volume (MPV) would be a profitable marker in predicting disease severity in adolescents with severe primary dysmenorrhea (PD). Design: A total of 67 patients diagnosed with PD and 37 healthy adolescents with regular
RI PT
menstrual cycles were included in the study. Hemoglobin, MPV, white blood cell count (WBC), platelet, lymphocyte, and neutrophil counts were measured as part of the automated complete blood examination. Neutrophil to lymphocyte ratio (NLR) and platelet to
SC
lymphocyte ratio (PLR) were obtained from the absolute neutrophil or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale (VAS) was
M AN U
used to assess the level of pain, as mild (60 mm) PD.
Results: The MPV level of the combined severity PD and control groups were similar. However, the MPV was significantly lower in the severe PD group compared to the control
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group (p = 0.04). There were no significant differences in the other hematological parameters between the groups. The mean VAS score of the PD and control subjects were 7.35 ± 2,25 and 1.07 ± 1,96, respectively (p < 0.01). There was a poor negative correlation, which was
EP
statistically insignificant, between MPV and WBC. Conclusion: The present study demonstrated that MPV is decreased in adolescents with
AC C
severe PD. Further studies with larger numbers of subjects are necessary to clarify the roles of platelets in the pathogenesis of severe PD and evaluate the changes in MPV value in response to treatment.
Keywords: Adolescent, primary dysmenorrhea, pelvic pain, mean platelet volume platelet, visual analog scale
ACCEPTED MANUSCRIPT Mean platelet volume as a novel biomarker for adolescents with severe primary dysmenorrhea
Introduction
RI PT
Dysmenorrhea is a leading gynecological complaint among adolescents, which can cause recurrent school or work absenteeism1. It usually presents with lower abdominal cramping accompanied by headaches or vomiting2. Dysmenorrhea in the absence of an
SC
organic pelvic pathology is primary dysmenorrhea (PD)3. PD symptoms typically begin a few hours before or after the onset of menstrual bleeding, and lasts approximately 48−72 hours
M AN U
with initial onset 6−12 months after menarche2. The cause of PD has not to date been fully elucidated. However, it has been suggested that excess prostaglandin activity can lead to increased uterine contraction and vasoconstriction of uterine vessels, resulting uterine ischemia in PD4, 5, 6. Ischemia in turn can trigger free radical accumulation, which can cause
TE D
endometrial damage and inflammation7. Inflammation may therefore also play an important role in the pathophysiology of PD8, 9.
The mean platelet volume (MPV), a component of a routine complete blood count, is a
EP
marker of platelet function and activity10. Decreased MPV levels have been reported to demonstrate disease activity and inflammatory burden in various inflammatory diseases11, 12, . Furthermore, a recent study reported low MPV values throughout the menstrual cycle in
AC C
13
PD patients compared to a control group14. The aim of the current preliminary study is to evaluate whether MPV would be a profitable marker in predicting disease severity in patients with PD. This might provide new insight into the pathogenesis of this common disease, which may be informative for new therapeutic developments.
Materials and methods Study population
ACCEPTED MANUSCRIPT This prospective cross sectional study was conducted at the Obstetrics and Gynecology Clinic, Dumlupinar University Evliya Celebi Training and Research Hospital, Kutahya, Turkey. The study was approved by the Ethics Committee at Dumlupinar University and conducted in accordance with the declaration of Helsinki and Good Clinical Practice
RI PT
guidelines. All participants provided informed written consent. Adolescent girls with regular menstrual cycles of 24−35 days and suffering from PD during at least in 50% of their menstrual cycles, were enrolled in the study. The diagnosis was made using patient history
SC
and through physical examination15. After systemic and gynecological evaluation of the study participants, exclusion criteria included the following: women taking medication in the
M AN U
previous 3 months; women using intrauterine contraception devices: patients suffering from a pelvic disorder causing dysmenorrhea; smoking; cardiovascular disease; clinical obesity; diabetes mellitus; malignancy; hematological, hepatic or thyroid disease; fibromyalgia; acute or chronic inflammatory diseases; any systemic disease; patients with a body mass index
TE D
(BMI) >29.
Hematological parameters
EP
Blood samples were obtained during the first 4 days of spontaneous menstrual cycle. Haemoglobin, MPV, white blood cell count (WBC), and platelet, lymphocyte, and neutrophil
AC C
counts were measured as part of the automated complete blood count in ethylene diamino tetra acetic acid tubes by using a Beckman Coulter LH 780 Hematology Analyzer (Beckman Coulter, Miami, Florida, USA). Analyzes were performed immediately after sampling to prevent in vitro platelet activation. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were obtained from the absolute neutrophil count or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale (VAS), a validated pain scale, was used to assess the level of pain16, 17, 18. The score itself is determined by measuring the distance from the left side of the
ACCEPTED MANUSCRIPT 100 mm scale to the point which the patient marked as the level of pain. The VAS score was classified as mild (60 mm) dysmenorrhea.
Statistical analysis
RI PT
Statistical Package for Social Sciences version 21.0 software for Windows (Chicago, IL, USA) was used for statistical analysis. All data are presented as mean ± standard deviation. The Kolmogorov-Smirnov test was used to analyze the data distribution. To
SC
determine differences between quantitative variables, an independent samples t-test was used. Data found to be abnormally distributed were analyzed using the Mann-Whitney U test for
M AN U
independent subgroups. For correlation analysis, Pearson’s correlation test was used. A pvalue 0.05
Day of cycle (mean ± SD)
28.0 ± 10.79
27.0 ± 10.22
p > 0.05
Parity (number)
0.51 ± 0.84
0.80 ± 0.61
p > 0.05
Abortion (number)
0.27 ± 0.79
0.58 ± 0.93
p > 0.05
Heart rate (beats per minute)
84.01 ± 7.36
85.96 ± 9.0
p > 0.05
Systolic blood pressure (mmHg)
111.85 ± 14.01
112.90 ± 11.88
p > 0.05
Diastolic blood pressure (mmHg)
59.83 ± 24.72
57.69 ± 30.98
p > 0.05
M AN U
SC
RI PT
PD group (n = 67)
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EP
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SD = standard deviation. BMI = body mass index. VAS = visual analog scale. PD = primary dysmenorrhea.
ACCEPTED MANUSCRIPT
Control group (n = 38)
p-value
WBC (/mm3 x 103)
7.69 ± 1.85
7.68 ± 2.16
p = 0.938
Platelet count (/mm3 x 103)
263.05 ± 72.86
279.71 ± 54.05
p = 0.234
Hemoglobin concentration (g/dl)
13.38 ± 1.25
12.70 ± 2.33
p = 0.67
MPV (fl)
8.46 ± 0.99
8.82 ± 1.23
p = 0.763
PLR
128.33 ± 41.57
132.85 ± 48.79
p = 0.634
NLR
2.38 ± 1.17
p = 0.42
RI PT
PD group (n = 67)
SC
Table 2. Hematological parameters of PD and control groups
2.21 ± 0.83
AC C
EP
TE D
M AN U
WBC = white blood cell count. MPV = mean platelet volüme. PLR = platelet to lymphocyte ratio. NLR = neutrophil to lymphocyte ratio.
ACCEPTED MANUSCRIPT Table 3. Comparison of hematological parameters between severe PD and control groups. Control group (n = 38)
p-value
MPV (fl)
8.26 ± 0.90
8.82 ± 1.23
p = 0.04
PLR
133.30 ± 42.00
132.85 ± 48.79
p > 0.05
NLR
2.39 ± 1.22
2.21 ± 0.83
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Severe PD group (n = 39)
p > 0.05
AC C
EP
TE D
M AN U
SC
PLR = platelet to lymphocyte ratio. NLR = neutrophil to lymphocyte ratio.
S1083-3188(16)00164-9
DOI:
10.1016/j.jpag.2016.01.128
Reference:
PEDADO 1961
To appear in:
Journal of Pediatric and Adolescent Gynecology
Received Date: 10 January 2016 Accepted Date: 31 January 2016
Please cite this article as: Kabil Kucur S, Seven A, Yuksel KB, Sencan H, Gozukara I, Keskin N, Mean Platelet Volume, a novel biomarker in adolescents with severe Primary Dysmenorrhea, Journal of Pediatric and Adolescent Gynecology (2016), doi: 10.1016/j.jpag.2016.01.128. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Mean Platelet Volume, a novel biomarker in adolescents with severe Primary Dysmenorrhea KABIL KUCUR Suna, Assist Prof, Dumlupinar University Medical Faculty Evliya Celebi Training and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani
RI PT
Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected], Gsm: +905323559047
SEVEN Ali, Assist Prof, Dumlupinar University Medical Faculty Evliya Celebi Training and
SC
Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected]
M AN U
YUKSEL Kadriye Beril, Assist Prof, Dumlupinar University Medical Faculty Evliya Celebi Training and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected] SENCAN Halime, Resident, Dumlupinar University Medical Faculty Evliya Celebi Training
TE D
and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, [email protected] GOZUKARA Ilay, Assist Prof, Mustafa Kemal University Medical Faculty, Department of
EP
Obstetrics and Gynecology, [email protected] KESKIN Nadi, Assoc. Prof, Dumlupinar University Medical Faculty Evliya Celebi Training
AC C
and Research Hospital, Department of Obstetrics and Gynecology, Okmeydani Street Evliya Celebi Avenue 43000, Kutahya, Turkey, nadi [email protected] Running title: Mean Platelet Volume in adolescents with Primary Dysmenorrhea
ACCEPTED MANUSCRIPT Abstract Study objective: To evaluate whether mean platelet volume (MPV) would be a profitable marker in predicting disease severity in adolescents with severe primary dysmenorrhea (PD). Design: A total of 67 patients diagnosed with PD and 37 healthy adolescents with regular
RI PT
menstrual cycles were included in the study. Hemoglobin, MPV, white blood cell count (WBC), platelet, lymphocyte, and neutrophil counts were measured as part of the automated complete blood examination. Neutrophil to lymphocyte ratio (NLR) and platelet to
SC
lymphocyte ratio (PLR) were obtained from the absolute neutrophil or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale (VAS) was
M AN U
used to assess the level of pain, as mild (60 mm) PD.
Results: The MPV level of the combined severity PD and control groups were similar. However, the MPV was significantly lower in the severe PD group compared to the control
TE D
group (p = 0.04). There were no significant differences in the other hematological parameters between the groups. The mean VAS score of the PD and control subjects were 7.35 ± 2,25 and 1.07 ± 1,96, respectively (p < 0.01). There was a poor negative correlation, which was
EP
statistically insignificant, between MPV and WBC. Conclusion: The present study demonstrated that MPV is decreased in adolescents with
AC C
severe PD. Further studies with larger numbers of subjects are necessary to clarify the roles of platelets in the pathogenesis of severe PD and evaluate the changes in MPV value in response to treatment.
Keywords: Adolescent, primary dysmenorrhea, pelvic pain, mean platelet volume platelet, visual analog scale
ACCEPTED MANUSCRIPT Mean platelet volume as a novel biomarker for adolescents with severe primary dysmenorrhea
Introduction
RI PT
Dysmenorrhea is a leading gynecological complaint among adolescents, which can cause recurrent school or work absenteeism1. It usually presents with lower abdominal cramping accompanied by headaches or vomiting2. Dysmenorrhea in the absence of an
SC
organic pelvic pathology is primary dysmenorrhea (PD)3. PD symptoms typically begin a few hours before or after the onset of menstrual bleeding, and lasts approximately 48−72 hours
M AN U
with initial onset 6−12 months after menarche2. The cause of PD has not to date been fully elucidated. However, it has been suggested that excess prostaglandin activity can lead to increased uterine contraction and vasoconstriction of uterine vessels, resulting uterine ischemia in PD4, 5, 6. Ischemia in turn can trigger free radical accumulation, which can cause
TE D
endometrial damage and inflammation7. Inflammation may therefore also play an important role in the pathophysiology of PD8, 9.
The mean platelet volume (MPV), a component of a routine complete blood count, is a
EP
marker of platelet function and activity10. Decreased MPV levels have been reported to demonstrate disease activity and inflammatory burden in various inflammatory diseases11, 12, . Furthermore, a recent study reported low MPV values throughout the menstrual cycle in
AC C
13
PD patients compared to a control group14. The aim of the current preliminary study is to evaluate whether MPV would be a profitable marker in predicting disease severity in patients with PD. This might provide new insight into the pathogenesis of this common disease, which may be informative for new therapeutic developments.
Materials and methods Study population
ACCEPTED MANUSCRIPT This prospective cross sectional study was conducted at the Obstetrics and Gynecology Clinic, Dumlupinar University Evliya Celebi Training and Research Hospital, Kutahya, Turkey. The study was approved by the Ethics Committee at Dumlupinar University and conducted in accordance with the declaration of Helsinki and Good Clinical Practice
RI PT
guidelines. All participants provided informed written consent. Adolescent girls with regular menstrual cycles of 24−35 days and suffering from PD during at least in 50% of their menstrual cycles, were enrolled in the study. The diagnosis was made using patient history
SC
and through physical examination15. After systemic and gynecological evaluation of the study participants, exclusion criteria included the following: women taking medication in the
M AN U
previous 3 months; women using intrauterine contraception devices: patients suffering from a pelvic disorder causing dysmenorrhea; smoking; cardiovascular disease; clinical obesity; diabetes mellitus; malignancy; hematological, hepatic or thyroid disease; fibromyalgia; acute or chronic inflammatory diseases; any systemic disease; patients with a body mass index
TE D
(BMI) >29.
Hematological parameters
EP
Blood samples were obtained during the first 4 days of spontaneous menstrual cycle. Haemoglobin, MPV, white blood cell count (WBC), and platelet, lymphocyte, and neutrophil
AC C
counts were measured as part of the automated complete blood count in ethylene diamino tetra acetic acid tubes by using a Beckman Coulter LH 780 Hematology Analyzer (Beckman Coulter, Miami, Florida, USA). Analyzes were performed immediately after sampling to prevent in vitro platelet activation. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were obtained from the absolute neutrophil count or platelet count, respectively, divided by the absolute lymphocyte count. The visual analog scale (VAS), a validated pain scale, was used to assess the level of pain16, 17, 18. The score itself is determined by measuring the distance from the left side of the
ACCEPTED MANUSCRIPT 100 mm scale to the point which the patient marked as the level of pain. The VAS score was classified as mild (60 mm) dysmenorrhea.
Statistical analysis
RI PT
Statistical Package for Social Sciences version 21.0 software for Windows (Chicago, IL, USA) was used for statistical analysis. All data are presented as mean ± standard deviation. The Kolmogorov-Smirnov test was used to analyze the data distribution. To
SC
determine differences between quantitative variables, an independent samples t-test was used. Data found to be abnormally distributed were analyzed using the Mann-Whitney U test for
M AN U
independent subgroups. For correlation analysis, Pearson’s correlation test was used. A pvalue 0.05
Day of cycle (mean ± SD)
28.0 ± 10.79
27.0 ± 10.22
p > 0.05
Parity (number)
0.51 ± 0.84
0.80 ± 0.61
p > 0.05
Abortion (number)
0.27 ± 0.79
0.58 ± 0.93
p > 0.05
Heart rate (beats per minute)
84.01 ± 7.36
85.96 ± 9.0
p > 0.05
Systolic blood pressure (mmHg)
111.85 ± 14.01
112.90 ± 11.88
p > 0.05
Diastolic blood pressure (mmHg)
59.83 ± 24.72
57.69 ± 30.98
p > 0.05
M AN U
SC
RI PT
PD group (n = 67)
AC C
EP
TE D
SD = standard deviation. BMI = body mass index. VAS = visual analog scale. PD = primary dysmenorrhea.
ACCEPTED MANUSCRIPT
Control group (n = 38)
p-value
WBC (/mm3 x 103)
7.69 ± 1.85
7.68 ± 2.16
p = 0.938
Platelet count (/mm3 x 103)
263.05 ± 72.86
279.71 ± 54.05
p = 0.234
Hemoglobin concentration (g/dl)
13.38 ± 1.25
12.70 ± 2.33
p = 0.67
MPV (fl)
8.46 ± 0.99
8.82 ± 1.23
p = 0.763
PLR
128.33 ± 41.57
132.85 ± 48.79
p = 0.634
NLR
2.38 ± 1.17
p = 0.42
RI PT
PD group (n = 67)
SC
Table 2. Hematological parameters of PD and control groups
2.21 ± 0.83
AC C
EP
TE D
M AN U
WBC = white blood cell count. MPV = mean platelet volüme. PLR = platelet to lymphocyte ratio. NLR = neutrophil to lymphocyte ratio.
ACCEPTED MANUSCRIPT Table 3. Comparison of hematological parameters between severe PD and control groups. Control group (n = 38)
p-value
MPV (fl)
8.26 ± 0.90
8.82 ± 1.23
p = 0.04
PLR
133.30 ± 42.00
132.85 ± 48.79
p > 0.05
NLR
2.39 ± 1.22
2.21 ± 0.83
RI PT
Severe PD group (n = 39)
p > 0.05
AC C
EP
TE D
M AN U
SC
PLR = platelet to lymphocyte ratio. NLR = neutrophil to lymphocyte ratio.
