Effects of age, gender and menstrual cycle on
platelet function assessed by impedance
aggregometry
Gösta Berlin, Mats Hammar, L. Tapper and Nahreen Tynngård
The self-archived postprint version of this journal article is available at Linköping
University Institutional Repository (DiVA):
http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-156901
N.B.: When citing this work, cite the original publication.
This is an electronic version of an article published in:
Berlin, G., Hammar, M., Tapper, L., Tynngård, N., (2019), Effects of age, gender and menstrual cycle
on platelet function assessed by impedance aggregometry, Platelets, 30(4), 473-479.
https://doi.org/10.1080/09537104.2018.1466387
Original publication available at:
https://doi.org/10.1080/09537104.2018.1466387
Copyright: Taylor & Francis (STM, Behavioural Science and Public Health Titles)
http://www.tandf.co.uk/journals/default.asp
Effects of age, gender and menstrual cycle on platelet function assessed by
impedance aggregometry
Berlin G1, Hammar M2, Tapper L1, Tynngård N3
1
Department of Clinical Immunology and Transfusion Medicine, and Department of Clinical
and Experimental Medicine, Linköping University, Linköping, Sweden
2
Department of Obstetrics and Gynaecology, and Department of Clinical and Experimental
Medicine, Linköping University, Linköping, Sweden
3
Research and Development Unit in Region Östergötland and Department of Medical and
Health Sciences, Linköping University, Linköping, Sweden
Corresponding author: Nahreen Tynngård; PhD
Research and Development Unit in Region Östergötland.
S:t Larsgatan 9D, 581 85 Linköping, Sweden,
Tel: +46 (0)10-1039773
Fax: +46 (0)10-103 85 01
E-mail: nahreen.tynngard@regionostergotland.se
Running head: Effects of age and gender on platelet function
Keywords: Platelet function, aggregation, age, gender, menstrual cycle
Abstract
Platelets are needed to prevent or arrest bleeding and aggregate at the site of injury upon
vascular damage. Platelets express receptors for estrogens which might affect the function of
the platelets and their haemostatic ability. The aim was to identify possible differences in
platelet function related to age, gender and phases of the menstrual cycle by use of impedance
aggregometry with Multiplate. In the first part of the study platelet function was assessed in
60 healthy individuals (30 men and 30 women) in each of three age groups (20-25, 40-45 and
60-65 years). In the second part of the study the platelet function was analysed on four
occasions during the menstrual cycle in women without oral contraceptives (n=17) and
compared to 19 women on oral contraceptives (OCs) and 18 men of similar age (20-40 years).
For the women on OCs, aggregation was analysed once during the tablet free week and once
late during the period with OCs. The men were sampled once. Women of younger age (< 45
years) had significantly higher agonist induced aggregation response than both men and postmenopausal women (60-65 years). The agonist induced aggregation response did not differ
between phases of the menstrual cycle or OC use. The results suggest that estradiol and/or
progesterone affect spontaneous aggregation since it was found to be lowest in the mid-luteal
phase. Spontaneous aggregation was significantly lower in women on OCs than in both men
and women without OCs. Our findings indicate that fertile age is associated with higher
aggregation response capacity of the platelets, possibly to prevent excessive bleeding during
menstruation, but this response capacity is not altered during the menstrual cycle or by use of
OCs.
Introduction
Platelets have an important role in the haemostatic process. Platelets adhere to proteins
exposed in the subendothelium resulting in platelet activation, shape change, secretion from
intracellular granules, and platelet aggregation which leads to sealing of the damaged vessel.
The function of platelets has been shown to be increased during pregnancy [1, 2], which could
be seen as a preparation for delivery. Estrogens are involved in the sexual and reproductive
function of women and their levels vary over the course of the menstrual cycle [3]. Women
have much higher levels of estrogens than men but the levels decrease following menopause
[4]. Since platelets express receptors for estrogens [5, 6], it is likely that estrogens could affect
the function of the platelets as a preparation for delivery but also for menstruation with
shedding of the endometrium. It has been shown that estrogens potentiate thrombin-induced
platelet aggregation [7]. There might thus be age, gender and menstrual cycle related
differences in platelet function.
However, conflicting results have been reported on the effect of age [8-12] and gender [8, 1215] on platelet function. Many of the studies were conducted using light transmission
aggregometry (LTA) [8, 9, 13, 15] which is considered to be the gold standard method to
assess platelet function. However, this method can only assess platelet function after the
platelets have been separated from whole blood and analysed as platelet rich plasma (PRP) or
as a washed platelet suspension. This sample preparation might affect the platelets and their
function [16].
A newer method, impedance aggregometry, enables analysis of platelet aggregation in whole
blood. Impedance aggregometry, using the instrument Multiplate, has gained popularity when
monitoring anti-platelet therapy [17]. This method might provide new insight on the effect of
age and gender on platelet since it makes analysis of whole blood possible without any
platelet sample preparation. Sex-related differences in platelet function with Multiplate have
been analysed only in a few studies with conflicting results [18-20].
This study investigates the effect of age, gender and changes in the sex-hormones during the
menstrual cycle on platelet function using impedance aggregometry (Multiplate). The
hypothesis is that platelet activity is higher for women than for men particularly during fertile
age and also is higher prior to menstruation than during the rest of the menstrual cycle.
Methods
The study was split into two parts. Part 1 aimed at assessing age and sex related differences in
platelet function and Part 2 to investigate the effects of changes in sex-hormones on platelet
function. The study was approved by the local ethical review board in Linköping, Sweden. All
participants received written and/or oral information of the study and gave their oral/written
informed consent to participate in the study.
Part 1
Sixty healthy individuals (30 men and 30 women), 20 in each of three age groups of 20-25
years (median age 24 for women, 22 for men), 40-45 (median age 44 for women, 43 for men)
and 60-65 (median age of 63 for women, 63 for men) were enrolled in the study based on
agreement of participation and fulfilling the inclusion criterion regarding age. Exclusion
criterion was intake of pharmaceuticals affecting platelets such as non-steroidal antiinflammatory drugs, acetyl salicylic acid, and platelet receptor antagonists. Blood was
collected in a 3.0-mL K2E Venosafe EDTA tube (Terumo Europe NV, Leuven, Belgium) for
analysis of haematology variables and in a 3.0-mL Hirudin tube (Roche Diagnostics GmbH,
Mannheim, Germany) for impedance aggregometry.
Part 2
Seventeen healthy women without oral or other hormonal contraceptives with a median age of
27 years (referred to as test women) were enrolled in the second part of the study to
investigate changes in platelet function during the menstrual cycle. To determine the effects
of the use of oral contraceptives (OCs), 19 healthy women on combined OCs (i.e. a
combination of a synthetic progestogen and also a synthetic estrogen or in some cases
estradiol) with a median age of 23 years (referred to as control women) were enrolled in the
study. To further investigate the effects of sex-related differences on platelet function, 18
healthy men (age 20 – 40 years, median age 30) were also included (referred to as control
men). The participants were selected based on agreement to participate and fulfilling the
inclusion criteria regarding age and use or non-use of OCs. Exclusion criteria were
pharmaceuticals affecting platelets and excessive nose or laceration bleeding as well as
remarkable bleeding during dental procedures.
The women without OCs (test women) were sampled four times during the menstrual cycle.
The first sample was collected during the early follicular phase, at a median of 1 day (range 03 days) from the onset of menstruation. The second was collected at the time of ovulation. To
verify that the women were close to ovulation a Clearblue luteinizing hormone (LH) test
(SPD, Swiss Precision Diagnostics GmbH, Geneva, Switzerland) was used after the first
sample had been collected. When the LH-test indicated ovulation, the second sample was
collected at a median of 0 days (range 0-2 days) from the positive LH-test. The third sample
(mid-luteal phase) was collected at a median of 7 days (range 6-9 days) after the positive LHtest and the fourth sample at a median of 2 days (range 1-3 days) before the next
menstruation. Figure 1 presents the sample times in relation to the normal changes in
estradiol, progesterone and LH during the menstruation cycle. The estradiol and progesterone
serum levels were assessed at each sampling occasion to verify the phase of the ovulatory
cycle. The women on OCs (control women) were sampled twice during the anticonception
cycle. The first sample was collected during the interlude of the anticonception cycle (after a
median of 5 days without OCs, range 2-6 days). The second sample was collected during the
period with OCs (after a median of 18 days with OCs, range 16-19 days). The men were
sampled once at a random time point.
Blood was collected in a 3.0-mL K2E Venosafe EDTA tube for analysis of haematology
variables, in a 3.0-mL Hirudin tube for impedance aggregometry and in a 3.5-mL serum tube
containing coagulation factors (BD Vacutainer; Becton Dickinson and Company, Franklin
Lakes, NJ, USA) for analysis of the hormone levels. For the test and control women, heavy
menstrual bleeding and number of days with sanitary protection during the menstruation were
recorded.
Haematology variables and hormone levels
Platelet concentration and haematocrit (Hct) were determined in the EDTA sample using a
haematology analyzer (Cell-Dyn Sapphire, Abbott Diagnostics Division, Abbot Park, IL,
USA) according to the accredited methods at the Department of Clinical Chemistry at the
University Hospital in Linköping.
The blood sample in the serum tube was allowed to coagulate for at least 30 min, followed by
centrifugation at 1800 x g for 10 min. The serum was aliquoted and stored at -80°C until
analysis. Estradiol, progesterone and testosterone were analysed with Cobas e 602 (Roche
Diagnostics Scandinavia AB, Bromma, Sweden) according to accredited methods at the
Department of Clinical Chemistry.
Impedance aggregometry
Platelets aggregation was assessed by impedance technology using Multiplate (Roche
Diagnostics). Multiplate measures platelets adhesion to the electrodes in the test cuvette after
stimulation of the platelets with a platelets agonist. The adhesion of the platelets to the
electrodes changes the electric resistance between the electrodes which is detected. The
aggregation response is followed for 6 min and the area under the curve (AUC) is determined
and used as a measure of aggregation [21].
For the analysis, 300 µL of pre-warmed 9 mg/mL NaCl (B.Braun, Melsungen, Germany) was
added to the test cuvette, followed by 300 µL of hirudin anticoagulated blood. The blood and
buffer were incubated under constant stirring for 3 min. This was followed by the addition of
20 µL of a platelets agonist (ADPtest, COLtest, or TRAPtest; Roche Diagnostics). In Part 2,
blood was also analysed without the addition of agonist (i.e. using 20 µL of 9 mg/mL NaCl
instead of any agonist) to assess spontaneous aggregation. Analysis of the spontaneous
aggregation made it possible to specifically investigate to what extent the response following
agonist stimulation was actually induced by the agonist. The final concentrations of the
agonists were 32 µM for TRAPtest, 6.5 µM for ADPtest, and 3.2 µg/mL for COLtest. The
aggregation response was followed for 6 min at 37ºC under constant stirring.
Statistics
Results are presented as median and 25th to 75th percentiles. Statistical comparisons were
made using IBM SPSS Statistics version 22.
Part 1
Comparisons between the different age groups were made separately for women and men
with the Kruskall-Wallis test and applying Mann-Whitney U test to determine which agegroups differed and Bonferroni post-hoc test to adjust for multiple comparisons. MannWhitney U test was used for comparison between men and women of the same age group. In
a separate analysis a comparison was made between men of all age groups (i.e. age 20-65),
menstruating women (i.e. age 20-45), and postmenopausal women (i.e. age 60-65) as well as
between these two female groups using Kruskall-Wallis test and applying Mann-Whitney U
test to determine which groups differed. Bonferroni post-hoc was used to adjust for multiple
comparisons.
Part 2
Friedman’s test was used for comparisons between the sample times of the women in the test
group and Wilcoxon signed rank test was applied to determine which sample times differed
using a Bonferroni post-hoc test to adjust for multiple comparisons. For comparisons between
the sampling times for the control women Wilcoxon’s signed rank test was used.
Comparisons between control women and test women were made between sample 1 for
control women and sample 1 for the test women as well as between sample 2 for control
women and sample 3 for test women using Mann-Whitney U-test. A mean was calculated for
all sampling times for each individual woman and used for the comparison with the men
applying the Mann-Whitney U test.
Results
Part 1
There was no difference in platelet count between the groups (Table I). Hct was significantly
higher in men than in women of the same age group (Table I). Hct was higher in women of
older age but remained unchanged in the men.
Women in the age group of 20-25 years had significantly higher agonist-induced aggregation
than women in the age group of 60-65 but there were no difference between the men of the
different age groups (Table I). The women of the younger age groups (20-25 and 40-45
years) also had significantly higher aggregation response than the men but there was no
difference between men and women in the oldest age group (60-65 years). A separate
comparison between men of all age groups (age 20-65), fertile women (age 20-45), and postmenopausal women (age 60-65) showed that men and older women had significantly lower
agonist-induced aggregation response than the younger women (Table II).
Part 2
The test women without OCs had a low estradiol level at the first sample time but had a
significant ovulatory phase increase. This was followed by a gradual decrease throughout the
rest of the menstrual cycle (Table III). All women had a progesterone level above the lower
reference limit for luteal phase (>13 mmol/L) at the third sampling occasion verifying that a
corpus luteum had developed and that ovulation had occurred prior to this sample occasion.
This was also the time when the highest progesterone levels were found. Testosterone was
low but significantly higher at the second (ovulatory) sample and was highest for 16 of the 17
women at this ovulatory sample time.
There were no changes in aggregation response throughout the menstrual cycle with
exception of spontaneous aggregation which was lowest at the third sampling time (Table III).
Women on OCs had no difference in aggregation response between the period with OCs
(sample 2) and the tablet-free week (sample 1).
Hct was shown to be slightly different between the groups with men having significantly
higher Hct than both control and test women (Table IV). The women on OCs had the highest
platelet count, significantly higher than for both men and women without OCs. However,
their spontaneous aggregation was shown to be lower than for both these groups (Table III
and IV). Women on and without OCs also had higher aggregation response than men but for
some agonists it was only significant after having adjusted for the spontaneous response
(Table IV). No difference was seen in the agonist-induced aggregation response between the
two groups of women, i.e. women with or without OCs (Table IV).
Eight women in the test group, but none in the OC group, reported that they experienced
heavy menstrual bleeding. The median number of days with sanitary protection was 6 [5-6]
for the test women and 5 [5-6] for the women on OCs.
Discussion
In Part 1 of this study we found that the older women (60-65 years) had significantly lower
aggregation response than the youngest women (20-25 years). In contrast, there was no
difference between age groups in males. Previous studies have reported conflicting results on
the association between age and platelets aggregation [8-10]. It is possible that discrepancies
between studies regarding the effect of age on platelet function could be due to the fact that in
some studies men and women were analysed in separate groups [8, 13, 22], in another study
men and women as one group [9] whereas in still another study only men were included [10].
This is supported by the fact that we found that younger women had significantly higher
aggregation response than men of the same age whereas we found no difference between men
and women in the 60-65 year age group. Part 2 of our study confirmed the results of Part 1
regarding a lower aggregation response of platelets from younger men compared with
younger women. Our hypothesis is that the higher reactivity of platelets in younger women as
compared with men and older, post-menopausal women is a way to prevent excessive blood
loss during menstruation.
Others have also reported higher platelet aggregation in younger women than in men as
analysed with LTA and Multiplate [14, 19, 20]. Testosterone has been shown to reduce
agonist-induced aggregation [14] which might explain the lower aggregation response found
in men than in younger women, even though it did not seem to have impact on the
spontaneous aggregation. However, in other studies no sex-related difference in aggregation
response was found with the two methods [15, 18]. Furthermore, Meade et al., in contrast to
our study, detected higher aggregation in both young and post-menopausal women compared
to men of similar age [8]. Differences between studies can be due to different methods to
assess aggregation (i.e. LTA vs. impedance technique), variations in agonist concentrations
[10, 22] and analysed aggregation variable (level of aggregation or the concentration of
agonist needed to induce a specific level of aggregation) as well as various age groups used in
the studies. Kasjanova et al. [10] reported that older age was associated with an increase in
aggregation but only when low dose of agonist was used. Furthermore, LTA is also affected
by pre-analytical factors including sample collection and preparation [16] and the separation
of PRP from whole blood can result in loss of platelets with higher density which could affect
the results.
The platelet count and Hct in the different groups in Part 1 were within the age and sex based
ranges established by our laboratory and similar to what has been published [23-25]. Both
Part 1 and 2 of our study showed that men had significantly higher Hct than women of all
ages which is consistent with the literature [23, 24]. The lower Hct found in women of fertile
age is likely due to regular blood loss through menstruations. However, the small differences
in Hct found in our study are unlikely to have had any impact on aggregation since others
have shown that Hct does not affect platelet aggregation when assessed by Multiplate [20, 2628].
Women on OCs were shown to have higher platelet count than men and women without OCs.
Aggregation response with Multiplate has been shown to be affected by platelet count [29-31]
with increase in aggregation with increasing number of platelets. The small differences found
in platelet count between the groups in this study most likely did not affect the results since
the platelet counts in all groups were within the normal range. At this level there is no or only
weak association between platelet count and aggregation [18, 27, 29] and aggregation is
believed to be dependent only on platelet function [29].
Furthermore, despite the higher platelet count, the women on OCs had lower spontaneous
aggregation response than both the men and the women without OCs. During the
anticonception period, the women are subjected to high levels of progestogen and estrogen
which might have caused the lower spontaneous aggregation since both substances have been
shown to inhibit aggregation [14, 32, 33]. However, use of OCs did not affect the agonistinduced aggregation which is in line with the results by Yee et al. who did not detect any
effect OCs on agonist-induced aggregation when assessed by LTA [34]. It may be that the
few days without use of OCs during the tablet-free week do not result in a high number of
new platelets with low exposition to sex steroids to appear in the circulation.
The agonist-induced aggregation response was not significantly altered by changes in the
level of estradiol, progesterone or testosterone during the menstruation cycle. This result is in
line with previous studies investigating agonist-induced changes during the menstrual cycle
with LTA [34, 35]. Using Multiplate differences in aggregation response during the menstrual
cycle were detected only when analysing changes as percentage of day 1 with lowest
aggregation in mid-luteal phase [19]. As in our study no difference was found using absolute
aggregation values during the cycle and the results varied depending on the type of agonist
used [19]. In contrast Teran et al. found that platelets were less reactive in the pre-ovulatory
phase than in the mid-luteal phase analysed with LTA and they also found that the result
depended on the agonist [36]. We found a decrease in spontaneous aggregation during the
cycle with lowest aggregation at the mid luteal phase, a time point associated with high levels
of progesterone since one week and high estradiol since three weeks. The results in our study
suggest that estradiol and progesterone may affect spontaneous aggregation, a variable rarely
studied when assessing aggregation. Spontaneous aggregation has been suggested to be
caused by ADP released from the red blood cells [37]. Whether the possible effect of estradiol
and progesterone on spontaneous platelet aggregation is caused by direct actions on the
platelets or by hormonal inhibition of ADP release from red blood cells needs to be further
studied.
A limitation in our study is that Part 1 is a small in vitro study with ten individuals in each age
and sex group and that we did not register the use of OCs or postmenopausal hormone
replacement therapy. It is a strength that the women without anticonception in Part 2 were all
shown to ovulate (according to LH-peak measurements and high progesterone in the midluteal phase). This is also confirmed by the highest testosterone levels in the ovulatory phase,
which is in line with previous findings of a mid-cycle testosterone peak [38].
The clinical importance of a higher platelet aggregation found in women of fertile age than in
postmenopausal women and men, is possibly a mechanism to prevent heavy menstrual
bleedings. However, platelet function does not seem to change rapidly enough to be detected
throughout the menstrual cycle with its changes in sex steroid levels or from use of oral OCs
to the tablet-free week.
Acknowledgement
We thank our collaborators at the Department of Clinical Chemistry and Clinical Immunology
and Transfusion Medicine at Linköping University Hospital for their assistance in the study.
Declaration of Interest
This study was supported by the grants from Region Östergötland. The authors report no other
declarations of interest.
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Table I. Part 1: Haematology variables and aggregation response of men and women of different age groups.
Women 20-25
Women 40-45
Women 60-65
Men 20-25
Men 40-45
Men 60-65
(n=10)
(n=10)
(n=10)
(n=10)
(n=10)
(n=10)
Platelet count (x109/L)
266 [240-297]
277 [225-325]
296 [260-301]
237 [229-282]
230 [204-255)]
241 [233-269]
Haematocrit (%)
39 [39-41]c
41 [40-42]
43 [42-43]a
45 (44-46]a
46 [45-47]b
44 [43-46]c
832 [752-887]c
847 [781-1079]
679 [581-743)a
676 [561-779]a
679 [581-743]b
572 [499-662]
Aggregation response
ADP-AUC (AU x min)
TRAP-AUC (AU x min) 1226 [1168-1315]c 1141 [1070-1348] 993 [916-1106]a 1048 [948-1115]a 993 [916-1106] 995 [843-1070]
COL-AUC (AU x min)
914 [801-951]
795 [755-988]
707 [612-790]
734 [679-840]a
666 [621-758]b
630 [556-757]
Results are presented as median and the 25th and 75th percentiles. Statistical comparisons were made between men and women of the same age
group as well as between the age groups for women and men separately with a = p <0.05 vs. women 20-25, b = p <0.05 vs. women 40-45 and c =
p <0.05 vs. women 60-65.
Table II. Part 1: Haematology variables and aggregation response for combined age groups of men and women.
Women 20-45
Women 60-65
Men 20-65
(n=20)
(n=10)
(n=30)
Platelet count (x109/L)
272 [233-307]
296 [260-301]
237 [223-272]
Haematocrit (%)
40 [39-42]b
43 [42-43]a
45 [44-47]ab
ADP-AUC (AU x min)
816 [750-903]b
679 [581-743]a
619 [510-729]a
TRAP-AUC (AU x min)
1205 [1107-1328]b 993 [916-1106]a
1010 [911-1126]a
COL-AUC (AU x min)
888 [789-1003]b
698 [603-817]a
Aggregation response
707 [612-790]a
Results are presented as median and the 25th and 75th percentiles. Statistical significant differences between the groups are shown with a = p
<0.05 vs. women 20-45 and b = p <0.05 vs. women 60-65.
Table III. Part 2: Haematology variables, hormone levels and aggregation results of the test women during the menstrual cycle and of control
women.
Test women S1
Day of menstrual cycle 1 [1-2]
Test women S2
Test women S3
Test women S4
15 [14-18]
22 [21-25]
26 [25-29]
267 [239-344]*
Contr. women S1 Contr. women S2
Estradiol (pM)
112 [103-138]†
764 [356-1265]*†
463 [383-577]*†
n.a
n.a
Progesterone (mM)
2.7 [2.2-3.9]†
3.5 [2.8-4.8]†
31.0 [28.3-40.7]*† 16.1 [11.3-17.2]* n.a
n.a
Testosterone (nM)
0.8 [0.6-1.0]
1.1 [1.0-1.5]*†
0.7 [0.6-0.9]
0.8 [0.7-0.9]
n.a
n.a
Platelet count (x109/L)
225 [222-248]a
242 [229-259]b
238 [212-257]
236 [224-258]
292 [238-330]a
286 [239-310]b
Haematocrit (%)
40 [37-41]a
39 [38-40]
40 [38-41]
39 [38-41]
42 [40-44]a
41 [41-42]*
Aggregation response, AUC (AU x min)
NaCl
142 [99-221]a
153 [63-223]b
102 [75-134]*
139 [116-172]
79 [50-130]a
65 [51-96]b
ADP
875 [773-915]
819 [718-890]
786 [729-874]
834 [753-906]
851 [716-898]
827 [759-851]
TRAP
1351 [1227-1421] 1346 [1194-1415]
1259[1232-1319] 1213[1175-1310] 1271 [1179-1315]
1308 [1163-1415]
Collagen
871 [761-927]
804 [784-855]
800 [730-839]
838 [771-871]
805 [784-969]
835[799-873]
ADP-NaCl
728 [631-770]
688 [586-796]
679 [602-820]
682 [616-726]
728 [652-818]
734 [652-818]
TRAP-NaCl
1206 [1019-1316] 1170 [1015-1295]
1184 [1071-1220] 1074 [992-1219] 1167 [10671252]
1191 [1091-1348]
Collagen-NaCl
715 [570-814]
695 [631-760]
771 [701-814]
721 [585-745]
692 [633-720]
738 [633-845]
Results are presented as median and the 25th and 75th percentiles within parenthesis (n=17 for test women i.e. women without oral contraceptives
and n=19 for control women i.e. women on oral contraceptives). The test women were sampled in early follicular phase (S1), at the time of
ovulation (S2), in mid-luteal phase (S3) and 1-3 days prior the next menstruation (S4). The control women were sampled during the OC free
week (S1) and during the OC period (S2). Statistical significant differences between sample times are shown for each group separately with * = p
< 0.05 vs. S1 and † = p < 0.05 vs. S4. Statistical significant differences are between control women and test women shown with a = p <0.05 for
S1 for test women vs. S1 for control women and b = p <0.05 for S3 for test women vs. S2 for control women. ADP-NaCl, TRAP-NaCl and
Collagen-NaCl are the agonist-induced response which has been corrected for spontaneous aggregation to NaCl.
Table IV. Part 2: Comparison of haematology variables and aggregation results of male controls, control women and test women.
Variable
Contr. men
Contr. women S1-S2
Test women S1-S4
Platelet count (x109/L)
237 [227-254]
289 [243-322]a
241 [220-255]
Haematocrit (%)
45 [42-47]
42 [39-43]a
39 [39-41]a
NaCl
161 [96-207]
81 [57-99]a
148 [104-177]
ADP
750 [642-817]
810 [751-878]
817 [754-894]
TRAP
1188 [1008-1292]
1282 [1177-1342]
1301 [1232-1339]a
Collagen
717 [669-832]
831 [789-910]a
820 [769-897]a
ADP-NaCl
599 [494-669]
731 [639-803]a
690 [627-757]a
TRAP-NaCl
1056 [832-1157]
1156 [1082-1280]a
1142 [1054-1262]
Collagen-NaCl
612 [450-675]
732 [693-828]a
711 [613-762]a
Aggregation response, AUC (AU x min)
Results are presented as median and the 25th and 75th percentiles within parenthesis (n=18 for men, n=17 for test women i.e. women without oral
contraceptives and n=19 for control women i.e. women on oral contraceptives). The test women were sampled in early follicular phase (S1), at
the time of ovulation (S2), in mid-luteal phase (S3) and 1-3 days prior the next menstruation (S4). The control women were sampled during the
OC free week (S1) and during the OC period (S2). Statistical differences between control men and control- and test women, respectively are
shown with a = p < 0.05 vs. control men. The mean results for all sampling times for each control- and test woman were used for the comparison
with the control men. ADP-NaCl, TRAP-NaCl and Collagen-NaCl are the agonist-induced response which has been corrected for spontaneous
aggregation to NaCl.