The effect of menstrual cycle on platelet aggregation in reproductive-age women

Our aim was to assess the change in platelet activity along the menstrual cycle. We conducted a prospective observational study. The study group included 16 healthy women with regular menstrual cycles, which were compared to a control group of 14 healthy males. Exclusion criteria were age <18 years or >45 years, use of oral contraceptives or any other forms of hormonal therapy and medical disorders or medications that might affect platelet aggregation. Blood samples were taken from each of the women at four different phases of the menstrual cycle: day 1 ± 1, day 7 ± 1, day 14 ± 1, and day 21 ± 1. A single blood sample was taken from the males. Platelet aggregation was assessed in whole blood samples using the Multiplate? analyzer with three different agonists (ADP, arachidonic acid (AA), and thrombin-receptor activating peptide (TRAP)). Platelet aggregation for each of the women at each of the phases of the menstrual cycle was expressed as the percentage change from the day 1 ± 1 value. A total of 390 aggregation assays were performed. The mean aggregation activity was significantly higher in females compared with males, irrespective of the agonist used. For the TRAP and the ADP agonists, the relative platelet activity decreased along the menstrual cycle from day 1 towards day 21 and from day 7 towards day 21, respectively, although differences reached statistical significance only for day 21 (?12.4% ± 3.2%, P < 0.05 for TRAP, and ?9.5% ± 3.9%, P < 0.05 for ADP). When using AA to induce platelet aggregation, the relative platelet activity was highest around the time of ovulation (11.0% ± 4.7%) and was significantly lower on day 21 (?8.5% ± 6.7%, P < 0.05). In conclusion, platelet aggregation activity is higher in females compared with males. The association between the phase of the menstrual cycle and platelet activity appears to vary with the type of agonist, but platelet aggregation is consistently lowest in the mid-luteal phase irrespective of the agonist used.     

Platelet aggregation in healthy women during normal pregnancy - a longitudinal study

Increased platelet activation is involved in obstetric complications such as preeclampsia and intrauterine growth retardation. It is of interest to study platelet aggregation during pregnancy, since increased aggregation theoretically could be a mechanism associated with placenta-mediated complications, which possibly could be prevented by drugs inhibiting platelet aggregation. There are, however, few robust studies describing platelet aggregation during normal pregnancy. The present longitudinal study was performed in order to study platelet aggregation during normal pregnancy resulting in a healthy child, during the puerperium and in nonpregnant, fertile women. Healthy, nonsmoking, pregnant women (n = 104), aged under 39 years and with BMI < 35, were followed during pregnancy and postpartum. Twenty-seven nonpregnant, non-puerperal, fertile women were studied for comparison. Platelet aggregation was determined with multiple electrode impedance aggregometry and analyzed at inclusion, 4 times during pregnancy and after at least 3 months postpartum. Platelet aggregation postpartum was compared with gestational weeks 8–15 and 37–40, respectively, and with nonpregnant, fertile women. Hemoglobin, leucocyte count, platelet count, prothrombin time, and activated partial thromboplastin time were determined at inclusion in order to verify normal hemostasis. Activation of platelets by arachidonic acid, adenosine diphosphate (ADP), and thrombin receptor activating peptide (trap-6) resulted in less aggregation during pregnancy, compared with postpartum (p < 0.03–< 0.001). Platelet aggregation following activation by collagen was unchanged. A minor increase in aggregation as pregnancy continued was found related to ADP (p < 0.021). Positive correlations were found between platelet counts and platelet aggregation. Postpartum platelet aggregation after activation with arachidonic acid, collagen, and trap-6 was lower than in the non-puerperal fertile state. Other hemostatic analyses were normal. In conclusion, there is a minor decrease in platelet aggregation after activation with arachidonic acid, trap-6, and ADP, measured with multiple electrode impedance aggregometry during normal pregnancy resulting in healthy babies, compared with the postpartum period. The small changes in platelet aggregation may be a consequence of a minor decrease in platelet count and probably lack clinical significance under normal conditions. Interindividual variations at certain time-points are substantial, which limits the usefulness of the multiple electrode impedance aggregometry for determining minor changes in platelet function.     

Effect of oral contraceptives and ovarian cycle on platelet function

In past decades, numerous epidemiological and clinical studies in women taking oral contraceptives revealed the impact of sex steroids on coagulation factors and the incidence of venous thrombosis. To date, only scarce data regarding the impact of oral contraceptives on platelet function are available. The aim of this study was to further elucidate the impact of sex steroids on platelet function. We conducted an observational study in young women using different types and dosages of monophasic oral contraceptives (OCs) compared to women not taking OCs. During the follicular phase, the mean closure time (CT) in Col/Epi was 168.0?±?64.9?s compared to 131.5?±?28.9?s during the luteal phase (p?=?0.012). In Col/Epi cartridges, no difference was detected between women taking second/third generation OCs and low-dose OCs (145.2?±?44.3 vs. 169.4?±?63.5, p?=?0.34). In contrast, mean Col/Epi values of women using anti-androgen-containing OCs were less (110.3?±?15.6?s) than in both other OC groups (p?=?0.03 for both comparisons). The same holds for Col/Epi values from women during the follicular- and luteal phases compared to women using anti-androgen-containing OCs (p?=?0.0002, p?=?0.013). Significant correlations between progesterone and platelet function in women not using OCs (p?=?0.02) could be found. In conclusion, the results of the study show that platelet function might be modulated by OCs and the female cycle. As for OCs, the main factor seems to be the progestagen. During the female cycle, the main impact on platelet function might be mediated by progesterone.     

Laboratory response to intranasal desmopressin in women with menorrhagia and platelet dysfunction

Summary.  Intranasal desmopressin (IN-DDAVP) is used for home treatment of menorrhagia in women with inherited bleeding disorders. The effect of IN-DDAVP on laboratory haemostatic parameters in women with menorrhagia related to platelet dysfunction is unknown. We evaluated the effects of IN-DDAVP on haemostatic parameters in women with menorrhagia and platelet dysfunction and correlated them with menstrual flow. Eleven women (aged 18–45) with menorrhagia and haemostatic abnormalities had determination of von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor (VWF:RCo) activity, factor VIII coagulant activity (FVIII:C), platelet aggregation and platelet adenosine tri-phosphate (ATP) release pre-IN-DDAVP and 60-min post-IN-DDAVP. Eight of eleven women underwent platelet function analyzer (PFA-100) closure time determination with collagen/adrenaline and collagen/adenosine diphosphate cartridges pretreatment and post-treatment. IN-DDAVP was administered during two consecutive menstrual cycles. Menstrual flow was assessed during each cycle using a pictorial blood assessment chart. Treatment with IN-DDAVP resulted in elevated VWF levels and shortened PFA-100 closure time with significant inverse correlation between shortening of PFA-100 closure times and increases in VWF levels. There were also significant inverse correlations between changes in menstrual flow and changes in VWF:Ag ( P  =   0.02), VWF:RCo ( P  =   0.04) and FVIII:C ( P  =   0.006), following treatment. In vitro platelet aggregation and platelet ATP release response did not correct and did not correlate with changes in menstrual flow. Our results demonstrate a correlation between haemostatic parameters and menstrual flow following IN-DDAVP in women with menorrhagia and platelet dysfunction.     

Hemostatic status and fibrinolytic response potential at different phases of the menstrual cycle.

Coagulation and fibrinolytic variables including platelet function and endogenous fibrinolytic response were determined in 30 normal healthy women volunteers not on any known medication during the period of study. They were between 18 years and 38 years old and had normal menstrual cycles of between 28 days and 30 days. Blood samples were obtained within one menstrual cycle and after having fasted overnight within days 1 to 3 (menstruation), 5 to 9 (follicular), 10 to 14 (mid-cycle), and 21 to 26 (luteal) of the menstrual cycle. Analysis of variance (ANOVA) showed no significant differences in the hemostatic parameters studied between the phases of the menstrual cycle except for a reduced D-dimer level at midcycle. Significant fibrinolytic response was seen after venous occlusion but they were not significantly different between the phases of the menstrual cycle. The women were then divided into either normal weight (n=22) or overweight (n=8) according to World Health Organization (WHO) classification and the data reanalyzed. Elevated tissue plasminogen activator antigen and plasminogen activator inhibitor-1 levels except at menstruation and total protein S except at follicular phase were observed in overweight women together with increased plasminogen level only at luteal phase. Significant endogenous fibrinolytic response seen during the menstrual cycle was not different between normal and overweight women. The study demonstrated that systemic coagulation, fibrinolysis, and platelet function were probably not influenced by natural hormonal changes occurring during the menstrual cycle except for an associated reduced fibrinolytic state at mid-cycle. The hemostatic system in this small group of healthy overweight women studied appeared to be physiologically compromised.     

Effect of oral contraceptives and ovarian cycle on platelet function

In past decades, numerous epidemiological and clinical studies in women taking oral contraceptives revealed the impact of sex steroids on coagulation factors and the incidence of venous thrombosis. To date, only scarce data regarding the impact of oral contraceptives on platelet function are available. The aim of this study was to further elucidate the impact of sex steroids on platelet function. We conducted an observational study in young women using different types and dosages of monophasic oral contraceptives (OCs) compared to women not taking OCs. During the follicular phase, the mean closure time (CT) in Col/Epi was 168.0 +/- 64.9 s compared to 131.5 +/- 28.9 s during the luteal phase (p=0.012). In Col/Epi cartridges, no difference was detected between women taking second/third generation OCs and low-dose OCs (145.2 +/- 44.3 vs. 169.4 +/- 63.5, p=0.34). In contrast, mean Col/Epi values of women using anti-androgen-containing OCs were less (110.3 +/- 15.6 s) than in both other OC groups (p=0.03 for both comparisons). The same holds for Col/Epi values from women during the follicular- and luteal phases compared to women using anti-androgen-containing OCs (p=0.0002, p=0.013). Significant correlations between progesterone and platelet function in women not using OCs (p=0.02) could be found. In conclusion, the results of the study show that platelet function might be modulated by OCs and the female cycle. As for OCs, the main factor seems to be the progestagen. During the female cycle, the main impact on platelet function might be mediated by progesterone.     

Performance trends in master freestyle swimmers aged 25–89 years at the FINA World Championships from 1986 to 2014

Performance trends in elite freestyle swimmers are well known, but not for master freestyle swimmers. We investigated trends in participation, performance, and sex difference in performance of 65,584 freestyle master swimmers from 25–29 to 85–89 years competing in FINA World Masters Championships between 1986 and 2014. The men-to-women ratio was calculated for each age group, and the trend across age groups was analyzed using single linear regression analysis. Trends in performance changes were investigated using a mixed-effects regression model with sex, distance, and calendar year as fixed variables. Participation increased in women and men in older age groups (i.e., 40 years and older). Women and men improved race times across years in all age groups and distances. For age groups 25–29 to 75–79 years, women were slower than men, but not for age groups 80–84 to 85–89 years. In 50, 100, and 200 m, women reduced the sex difference from 1986 to 2014 in age groups 30–34 to 75–79 years. In 400 m, women reduced the gap to men across time in age groups 40–44, 45–49, and 55–59 years. In 800 m, sex difference became reduced across time in age groups 55–59 and 70–74 years. In summary, participation increased from 1986 to 2014 in women and men in older age groups, women and men improved across time performance in all distances, and women were not slower compared to men in age groups 80–84 to 85–89 years. We expect a continuous trend in increasing participation and improved performance in master freestyle swimmers.     

Iron-dependent erythropoiesis in women with excessive menstrual blood losses and women with normal menses

In women of fertile age, iron loss consequent to excessive menstrual discharge is by far the most frequent cause of iron-deficient anemia. However, the relationship between menstrual discharge and iron loss is poorly understood. In this prospective study, total menstrual and iron losses were assayed in a large cohort of non-anemic women and women with excessive menstrual blood losses (menorrhagia) in order to provide data useful for intervention. One hundred and five Caucasian women aged 20–45 years were recruited. Blood cell count and serum ferritin (SF) levels were determined in each case before menses. Menstrual fluid losses (MFL) were determined using a standardized pads’ weight method. Hematin concentration was assayed by a variant of the Alkaline Hematin Method from which iron concentration was calculated. Mean SF levels were 36.2 (range 8.6–100) ng/ml in healthy women and 6.4 (range 5–14) ng/ml in patients with menorrhagia. Median values of iron lost/cycle were 0.87 mg in healthy women and 5.2 mg in patients with menorrhagia (ranges 0.102–2.569 and 1.634–8.665 mg, respectively, p?<?0.001). In women with menorrhagia, iron lost/cycle strongly correlated (0.789, p?<?0.001) with MFL. In conclusion, healthy women with normal menses lose, on average, 1 mg iron/cycle. Average iron losses in patients with menorrhagia are, at least in our cohort, on average, five-to-six times higher than normal. Most women with menorrhagia had totally depleted iron stores. Indirect, quantitative evaluation of iron lost with menses may be useful to assess the risk of developing iron-deficient anemia in individual patients.     

The effects of storage on platelet function in different blood products

Objectives: Reduced platelet (PLT) function during storage has been shown for buffy-coat-derived platelet concentrates (BCP) and apheresis platelet units (AP), while for whole blood (WB) it has not been well studied. The aim of this study was to investigate PLT function in these blood products throughout storage using a novel flow cytometric assay.

Methods: Flow cytometric measurement of agonist-induced platelet aggregation, CD62P expression and PAC-1 binding during storage in BCP, AP (1–9 days at 20°C) and WB (1–21 days at 2–6°C).

Results: PLT-aggregation capacity decreased from day 1 to day 7 for almost all product–agonist combinations (P?=?.004 to P?=?.029) with aggregation capacity of WB being similar to that of AP and BCP. WB aggregation capacity remained relatively unchanged from day 7 to day 21. For all blood products, the fraction of agonist-induced CD62P-expression remained high and the fraction of PAC-1 binding decreased during storage. WB PLTs underwent only small changes in CD62P expression and PAC-1 binding from day 7 to day 21.

Conclusion: This study found PLT aggregation in WB stored at 4°C to be as least as good as for BCP and AP stored at 20°C. WB retained significant PLT-aggregation capacity to day 21.     

Secondary Platelet Aggregation: A Quantitative Study

The lowest concentration of ADP and adrenaline which resulted in a secondary wave of platelet aggregation at 37°C was determined in 60 normal subjects. The range of such 'threshold' concentrations was 0.2–1.4μM for ADP and 0.1–1.0μM for adrenaline. The mean threshold concentration of each reagent was unrelated to age but was higher for men than for women; this difference disappeared when the results were corrected for the effect of differences in PCV on the citrate concentration in platelet-rich plasma. The variation between separate determinations of threshold concentration in the same individual was of the same order as that between individuals; no evidence was found that the threshold concentration of either reagent was related to the phase of the menstrual cycle in four young women tested repeatedly. There was a highly significant correlation between the threshold concentrations of the two reagents in individual subjects.
No correlation was found between the threshold concentration of either reagent and the total platelet ATP, ADP or ATP: ADP ratio. Concentrations of adrenaline at or slightly above the threshold caused the release of up to about 50% of the platelet ADP and 25% of the ATP during the second phase of aggregation, while lower concentrations produced no significant release.
The ultrastructural changes during the first phase of aggregation were similar with all concentrations of ADP tested; threshold concentrations and above caused dense packing of platelets during the second phase, with the formation of giant pseudopodia and no tendency to disaggregation during the period of observation, while at lower concentrations disaggregation was accompanied by a retraction of pseudopodia. There was no clear evidence of platelet degranulation during either first or second phase aggregation.     

Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort

BACKGROUND: Platelets are involved in myocardial infarction but evidence of prediction of infarction by measures of platelet function are sparce. METHODS: Platelet aggregation to thrombin and to ADP in platelet rich plasma was recorded for 2176 men aged 49-65 years in the Caerphilly cohort study. RESULTS: Results from 364 men were excluded, 80 of whom had not fasted before venepuncture; most of the others were excluded because antiplatelet medication had been taken shortly before the platelet tests. During the five years following the platelet tests 113 ischaemic heart disease (IHD) events which fulfilled the World Health Organisation criteria were identified--42 fatal and 71 non-fatal. No measure of platelet aggregation was found to be significantly predictive of incident IHD. The possibility that platelet function is predictive for only a limited time after it is characterised, and that prediction falls off with time, was tested. When IHD events are grouped by their time of occurrence after aggregation had been measured, the test results show a gradient suggestive of prediction of early IHD events. Thus, 24% of the men who had an event within 500 days of the test had had a high secondary response to ADP while only 12% of those whose IHD event had been 1000 or more days after the test had shown a high platelet response at baseline. The trend in these proportions is not significant. CONCLUSIONS: Platelet aggregation to thrombin and ADP in platelet rich plasma was recorded in the Caerphilly cohort study. No measure of aggregation was found to be predictive of IHD.     

Respiratory activity of genioglossus. Interaction between alcohol and the menstrual cycle

Alcohol consistently decreases genioglossal electromyographic (EMG) activity in awake men, but in women this response is more variable, possibly because of the menstrual cycle. To assess the interaction between alcohol and the menstrual cycle on genioglossal EMG activity, we measured ventilation and genioglossal EMG activity in 9 normal women before and after they drank 1 ml/kg alcohol. The effect of alcohol on ventilation and genioglossal EMG activity was studied twice in each subject: once during the follicular phase and again during the luteal phase of the menstrual cycle. Measurements were made while the subjects breathed room air and rebreathed a hypercapnic gas mixture. The ventilatory response to CO2 was significantly greater during the luteal phase of the menstrual cycle. Alcohol had no effect on resting ventilation or the ventilatory response to CO2 during either phase of the menstrual cycle. However, alcohol significantly decreased peak integrated genioglossal EMG activity during the follicular (low progesterone) phase but not during the luteal (high progesterone) phase of the cycle. The relative alcohol resistance of genioglossal EMG activity during the luteal phase may explain in part the low incidence of sleep-disordered breathing in premenopausal women and the benefit that some male patients with obstructive sleep apnea have derived from treatment with progesterone.     

Estrogen dependence of the periovulatory plasma prolactin response to gonadotropin-releasing hormone in normal women

It has been previously reported that GnRH is capable of inducing a PRL response in intact and castrated men treated with estradiol benzoate for 8–9 days. To further support the hypothesis of an estrogen-dependence of the PRL response to GnRH, GnRH was administered, either as a bolus or as a continuous infusion, to 45 normal women during various phases of their menstrual cycles. Synthetic GnRH (100 μg intravenous bolus) elicited a significant increase (mean 175%) in circulating PRL levels in nine women studied during the periovulatory phase of the menstrual cycle (days 14–17). Similarly, GnRH infusion (0.2 μg/min × 3 h) induced a PRL response (mean 148%) in six women studied during the same period. In contrast, saline infusion induced a modest decrease (37%) in plasma PRL levels in five women studied during the periovulatory period. No significant changes in circulating PRL levels were found after GnRH administration as a bolus or a continuous infusion, in 13 women during the late follicular phase (days 10–13) and in 12 women during the midluteal phase (days 21–24). Synthetic GnRH elicited the expected increase in gonadotropin levels during all phases of the cycle studied. The maximal response was found for both LH and FSH during the periovulatory phase of the cycle. In conclusion, the data confirm that GnRH is capable of stimulating a PRL response in humans and again suggest that this response is estrogen-dependent. Finally, a temporal correlation between the midcycle gonadotropin peak and the positive PRL response to exogenous GnRH has been established.     

Modulation of plasma endothelin levels by the menstrual cycle

Blood pressure varies during the menstrual cycle, but the reason for this is unclear. Administration of (synthetic) sex hormones can influence the level of vasoactive substances such as endothelin (ET). However, it is not known whether short-term variations in sex hormone levels in physiological situations affect ET levels. We assessed the effects of the menstrual cycle on plasma ET-1 in 8 healthy premenopausal women not using oral contraceptives (OCs) and 8 premenopausal women using OCs. ET-1 levels were measured in all subjects on days 1 to 3 (menstrual phase), 9 to 12 (follicular phase), and 20 to 23 (luteal phase) of the menstrual cycle. ET-1 levels remained constant in OC users (2.4 +/- 0.4, 2.6 +/- 0.4, and 2.4 +/- 0.4 pg/mL on days 1 to 3, 9 to 12, and 20 to 23 of the pill cycle). In contrast, ET-1 levels in non-OC users decreased in all women during the follicular and luteal phase of the menstrual cycle compared with the menstrual (low-estrogenic) phase (3.6 +/- 0.5, 2.8 +/- 0.5, and 2.9 +/- 0.3 pg/mL for the menstrual, follicular, and luteal phase, respectively, P < .01 for menstrual vfollicular and P < .01 for menstrual v luteal). The differences between OC users and nonusers were significant in the menstrual phase of the cycle (P < .01). We conclude that ET levels fluctuate during the menstrual cycle. Previously reported effects of the menstrual cycle on blood pressure may be partly explained by the effects of sex hormones on the level of vasoactive mediators. This fluctuation is not present in OC users. Studies on hemodynamic parameters in premenopausal women should account for hormonal variations in the various phases of the menstrual cycle.     

Lack of menstrual cycle effects on hypothalamic-pituitary-adrenal axis response to insulin-induced hypoglycaemia

OBJECTIVE: Limited data are available on the effects of the menstrual cycle on the hypothalamic-pituitary-adrenal axis (HPA) function. This study evaluates HPA axis reactivity to insulin-induced hypoglycaemia over the menstrual cycle. PATIENTS: Twelve normal women were randomized to placebo and evaluated during three successive menstrual cycles. Menstrual phase was documented by menstrual diary and by oestradiol and progesterone levels at the time of each insulin tolerance test (ITT). Six normal men were included as a comparison in the statistical analysis. MEASUREMENTS: Afternoon ITTs were performed initially on the second or third day of menses in women, then seven more ITTs followed at one or two week intervals during the next 10 weeks. Serum measurements of glucose, adrenocorticotrophin (ACTH) and cortisol were obtained. RESULTS: The glucose and ACTH responses to the ITTs were similar between men and women. Cortisol levels at baseline and during the test were higher in men than in women, although the amount of change was similar. Glucose, ACTH and cortisol response to insulin-induced hypoglycaemia did not vary over the menstrual cycle or during repeat testing in men or women. CONCLUSIONS: These data show that it is unnecessary to control for menstrual cycle during insulin tolerance tests performed at 1600 hours. It is, however, necessary to control for the effect of sex on cortisol levels. Repeat testing more than one week apart does not appear to influence the glucose, ACTH or cortisol response to insulin stress.     

Effects of Menstrual Cycle on Cardiac Autonomic Innervation As Assessed By Heart Rate Variability

Objective: The aim of the study was to investigate the effects of menstrual cycle on cardiac autonomic function parameters in young healthy women by means of heart rate variability (HRV). Methods: Forty‐three nonobese regularly cycling women (age 29 ± 6, range 20–38) were enrolled. Recordings for HRV analysis were obtained during the two phases of the menstrual cycle when the estrogen and progesterone levels peaked (follicular phase 11 ± 1 days and luteal phase 21 ± 1 days from the start of bleeding). Power spectral analysis of HRV was performed to calculate the low frequency peak (LF, 0.04–0.15 Hz), high frequency peak (HF, 0.15–0.40 Hz), LF in normalized unit (LF nU), HF in normalized unit (HF nU), and LF/HF ratio during the two phases of menstrual cycle. Results: The heart rates, LF and HF, were similar in both phases (P > 0.05). A significant increase was noted in the LF NU in the luteal phase compared to follicular phase of the menstrual cycle (P = 0.014), whereas a tendency for increased HF NU was observed in the follicular phase (P = 0.053). Furthermore, LF/HF ratio was significantly higher in the luteal phase compared to follicular phase (2.1 ± 1.5 vs 1.6 ± 0.9, P = 0.002), suggesting increased sympathetic activity in the luteal phase. Conclusion: We concluded that regulation of autonomic tone is modified during menstrual cycle. The alteration in the balance of ovarian hormones might be responsible for these changes in the cardiac autonomic innervation. A.N.E. 2002;7(1):60–63     

Platelet inhibition by aspirin 81 and 325 mg/day in men versus women without clinically apparent cardiovascular disease

Compared with men, women have greater platelet aggregation before and after low-dose aspirin. It is not known whether high-dose aspirin therapy brings residual platelet aggregation in women closer to that in men. Our objective was to compare inhibition of platelet aggregation in women and men after low- and high-dose aspirin. We enrolled healthy subjects (n=106) in a trial of 14 days of aspirin 81 mg/day followed by 14 days of 325 mg/day. Platelet function was measured at baseline and after the 2 aspirin doses. Women had greater baseline platelet activation measurements. After the 2 aspirin doses, men and women had near complete suppression of platelet aggregation to arachidonic acid in whole blood and in platelet-rich plasma (PRP), the direct cyclo-oxygenase-1 pathway affected by aspirin. For indirect pathways, women had significantly greater residual platelet activation to collagen and adenosine diphosphate (ADP) in whole blood after the 2 aspirin doses and in response to collagen and ADP in PRP after aspirin 325 mg/day only. After aspirin 325 mg/day, women continued to have greater residual platelet aggregation compared with men after aspirin 81 mg/day in response to collagen (p=0.016 in whole blood, p=0.037 in PRP), ADP (p<0.001 in whole blood, p=0.012 in PRP), and epinephrine (p=0.03 in PRP). Excretion of urinary thromboxane metabolite (urinary 11-dehydrothromboxane B2) decreased after aspirin to a similar extent in men and women. In conclusion, women continue to have greater residual platelet activity after high-dose aspirin compared with men treated with a lower dose of aspirin.     

The prevalence of rheumatoid arthritis in Estonia: an estimate based on rheumatology patients’ database

Sound epidemiological data are a basic requirement for decision making on the allocation of health care resources. Unfortunately, this is not the case in Estonia, where the paucity of epidemiological data has impeded health care planning for rheumatic conditions. The current paper presents the first effort to explore the epidemiology of rheumatoid arthritis (RA) in Estonia. Electronic databases of all rheumatology units of Harju County, three national and one private, were searched for the records of RA (ICD-10 diagnoses M05 and M06.0) patients who had visited a rheumatologist during 2006 or 2007. Prevalence of RA was calculated for the age 20 years and older and for subsets according to age and gender, using the numbers from the patients’ database in the numerator and the corresponding population numbers in the denominator. The total number of prevalent RA cases was 1,897, of which 85 % (n = 1,605) were women. The overall crude period prevalence 2006–2007 of RA in Harju County for the age group 20 years and older was 0.46 %. RA prevalence for both sexes increased with age until the age of 70–79 years and decreased subsequently. Prevalence of RA was significantly higher for women compared with men in all age groups. The prevalence of RA among women and men 20 years and older was 0.70 % (6.68–7.37) and 0.16 % (1.42, 1.79), respectively. Age-standardized (European population) prevalence rate was 0.44 %. The results are concordant with epidemiological data on RA prevalence derived recently in other European countries.     

Platelet reactivity in patients undergoing transcatheter aortic valve implantation

Thromboembolic events, primarily stroke, might complicate transcatheter aortic-valve implantation (TAVI) procedures in 3–5 % of cases. Thus, it is common to administer aspirin and clopidogrel pharmacotherapy for 3–6 months following TAVI in order to prevent those events. The biologic response to the dual anti platelet treatment (DAPT) is heterogeneous, e.g. low response, known as high on treatment platelet reactivity (HTPR) may be associated with adverse thromboembolic events. Little is known about the prevalence of HTPR among patients undergoing TAVI. To assess the variability in response and rates of residual platelet reactivity in patients undergoing TAVI. We examined platelet reactivity in response to clopidogrel and aspirin in 40 consecutive patients (mean age 81.7 ± 6.5 years, 66.7 % women) who underwent successful TAVI using the VerifyNow P2Y12 assay and the multiple electrode aggregometry assay (Multiplate analyzer) in response to adenosine diphosphate and arachidonic acid respectively, at different time points before and following TAVI. Before TAVI, the majority of patients were on antiplatelet therapy (68.5 % aspirin, 12.5 % clopidogrel, 12.5 % DAPT). Following the procedure all patients were on DAPT or clopidogrel and warfarin. Among analyzed patients, 41 % had HTPR for clopidogrel and 12.5 % for aspirin at baseline, which did not significantly change 1-month following the procedure (p = 0.81 and p  = 0.33, respectively). In conclusion, patients undergoing TAVI for severe aortic stenosis and treated with DAPT have high rates of residual platelet reactivity during the peri-procedural period and up to 1-month thereafter. These findings may have clinical implications for the anti-platelet management of TAVI patients.     

The influence of gender, age, and the menstrual cycle on plasma atrial natriuretic peptide

To examine the influence of gender, age, and the menstrual cycle on atrial natriuretic peptide (ANP) levels, we measured daily levels of ANP, aldosterone, estrogen, and progesterone in 13 young women (ages 25-35 yr) during the luteal phase of the menstrual cycle and daily ANP and aldosterone levels in 9 young men (ages 25-43 yr) for 10 consecutive days. In addition, fasting plasma ANP levels were assayed in 12 elderly male (ages 62-86 yr) and 9 elderly female subjects (ages 64-80 yr) on at least two separate occasions. The average daily ANP levels in the young women were much higher than those in the men (68.1 +/- 5.5 vs. 39.8 +/- 3.4 pmol/L; P less than 0.001), although no cyclical changes in ANP levels were observed. ANP levels were 94.0 +/- 17.9 pmol/L in elderly men and 78.3 +/- 19.4 pmol/L in elderly women. Aldosterone levels were higher in women than men during the luteal phase of the menstrual cycle (1154 +/- 125 vs 488 +/- 42 pmol/L; P less than 0.001), but not during the periovulatory period (580 +/- 103 pmol/L) or during menses (563 +/- 61 pmol/L). In conclusion, ANP levels in young women average approximately twice those in young men, but do not fluctuate with the cyclical changes in estrogen, progesterone, and aldosterone seen during the menstrual cycle. However, ANP levels in postmenopausal women are not greater than those in age-matched elderly men. Thus, gender appears to affect the secretion or metabolism of ANP during the premenopausal years of life.